guselkumab: prescribing information – dosing, contraindications, interactions, side effects

Paediatric plaque psoriasis
Tremfya is indicated for the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of 6 years who are candidates for systemic therapy.

Adult plaque psoriasis
Tremfya is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.
Paediatric plaque psoriasis
Tremfya is indicated for the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of 6 years who are candidates for systemic therapy.
Psoriatic arthritis
Tremfya, alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy (see section 5.1).
Ulcerative colitis
Tremfya is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response, or were intolerant to either conventional therapy, or a biologic treatment.

Crohn’s disease
Tremfya is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment.

Adult plaque psoriasis
Tremfya is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.
Psoriatic arthritis
Tremfya, alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adult patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug (DMARD) therapy (see section 5.1).
Ulcerative colitis
Tremfya is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response, or were intolerant to either conventional therapy, or a biologic treatment.

Crohn’s disease
Tremfya is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment.

Ulcerative colitis
Tremfya is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response, or were intolerant to either conventional therapy, or a biologic treatment.
Crohn’s disease
Tremfya is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment.

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of plaque psoriasis.
Posology
The 45 mg/0.45 mL pre-filled pen is for paediatric patients 6 years and older with a body weight less than 40 kg.
Each pre-filled pen is for single use in a single patient, and should be discarded immediately after use.
Paediatric plaque psoriasis (6 to 17 years)
Children from the age of 6 years with a body weight less than 40 kg
The recommended dose is shown below in Table 1, up to a maximum of 45 mg, administered by subcutaneous injection at Weeks 0 and 4, followed by a maintenance dose every 8 weeks (q8w).

Table 1:
Recommended dose of guselkumab for subcutaneous injection in paediatric patients with body weight less than 40 kg Body Weight (kg) (at time of dosing) Dose (mg) 12-15 kg 16-19 kg 20-23 kg 24-26 kg 27-30 kg 31-39 kg Children from the age of 6 years with a body weight of 40 kg or more For children with a body weight of 40 kg, or more a 100 mg pre-filled syringe is available. For the posology and method of administration, see section 4.2 of the Tremfya 100 mg pre-filled syringe Summary of Product Characteristics.
Consideration should be given to discontinuing treatment in paediatric patients who have shown no response after 24 weeks of treatment.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.
Special populations
Renal or hepatic impairment
Tremfya has not been studied in these patient populations. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies, and no dose adjustments are considered necessary. For further information on elimination of guselkumab, see section 5.2.
Paediatric population
The safety and efficacy of Tremfya in patients less than 6 years have not been established.
No data are available.
Method of administration
Subcutaneous use only. If possible, areas of the skin that show psoriasis should be avoided as injection sites.
Tremfya is not intended for self-administration by paediatric patients. After proper training in subcutaneous injection technique, a caregiver may inject Tremfya if a physician determines that this is appropriate. However, the physician should ensure appropriate medical follow-up of patients.
Caregivers should be instructed to inject the prescribed amount of solution according to the ‘Instructions for use’ provided in the carton.
For instructions on preparation of the medicinal product before administration, see section 6.6.

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which it is indicated.
Posology
Adult plaque psoriasis
The recommended dose is 100 mg by subcutaneous injection at Weeks 0 and 4, followed by a maintenance dose every 8 weeks (q8w).
Consideration should be given to discontinuing treatment in patients who have shown no response after 16 weeks of treatment.
Paediatric plaque psoriasis (6 to 17 years)
Children from the age of 6 years with a body weight of 40 kg or more
The recommended dose is 100 mg by subcutaneous injection at weeks 0 and 4, followed by a maintenance dose every 8 weeks (q8w).
Children from the age of 6 years with a body weight less than 40 kg
For children with a body weight less than 40 kg a 45 mg/0.45 mL pre-filled pen is available. For the posology and method of administration, see section 4.2 of the Tremfya 45 mg/0.45 mL pre-filled pen Summary of Product Characteristics.
Consideration should be given to discontinuing treatment in paediatric patients who have shown no response after 24 weeks of treatment.
Psoriatic arthritis
The recommended dose is 100 mg by subcutaneous injection at Weeks 0 and 4, followed by a maintenance dose every 8 weeks. For patients at high risk for joint damage according to clinical judgement, a dose of 100 mg every 4 weeks (q4w) may be considered (see section 5.1).
Consideration should be given to discontinuing treatment in patients who have shown no response after 24 weeks of treatment.
Ulcerative colitis
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg concentrate for solution for infusion.
or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg solution for injection.
After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 200 mg dose, see SmPC for Tremfya 200 mg solution for injection.

Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Crohn’s disease
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4, and Week 8. See SmPC for Tremfya 200 mg concentrate for solution for infusion.
or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg solution for injection.
After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose regimen of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 200 mg dose, see SmPC for Tremfya 200 mg solution for injection.
Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.
Special populations
Elderly
No dose adjustment is required (see section 5.2).
There is limited information in patients aged ≥65 years and very limited information in patients aged ≥75 years (see section 5.2).
Renal or hepatic impairment
Tremfya has not been studied in these patient populations. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies, and no dose adjustments are considered necessary. For further information on elimination of guselkumab, see section 5.2.
Paediatric population
The safety and efficacy of Tremfya in patients less than 18 years with ulcerative colitis, Crohn’s disease and psoriatic arthritis and in patients less than 6 years with psoriasis have not been established.
No data are available.
Method of administration
Subcutaneous use only. Sites for injection include the abdomen, thigh and back of the upper arm.
Tremfya should not be injected into areas where the skin is tender, bruised, red, hard, thick or scaly. If possible, areas of the skin that show psoriasis should be avoided as injection sites.

After proper training in subcutaneous injection technique, adult patients or caregivers may inject Tremfya if a physician determines that this is appropriate. However, the physician should ensure appropriate medical follow-up of patients. Adult patients or caregivers should be instructed to inject the full amount of solution according to the ‘Instructions for use’ provided in the carton. Tremfya is not intended for self-administration by paediatric patients.
For instructions on preparation of the medicinal product before administration, see section 6.6.

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which it is indicated.
Posology
Plaque psoriasis
The recommended dose is 100 mg by subcutaneous injection at Weeks 0 and 4, followed by a maintenance dose every 8 weeks (q8w).
Consideration should be given to discontinuing treatment in patients who have shown no response after 16 weeks of treatment.
Psoriatic arthritis
The recommended dose is 100 mg by subcutaneous injection at Weeks 0 and 4, followed by a maintenance dose every 8 weeks. For patients at high risk for joint damage according to clinical judgement, a dose of 100 mg every 4 weeks (q4w) may be considered (see section 5.1).
Consideration should be given to discontinuing treatment in patients who have shown no response after 24 weeks of treatment.
Ulcerative colitis
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg concentrate for solution for infusion.
or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg solution for injection.
After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 200 mg dose, see SmPC for Tremfya 200 mg solution for injection.
Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Crohn’s disease
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4, and Week 8. See SmPC for Tremfya 200 mg concentrate for solution for infusion.
or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg solution for injection.

After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose regimen of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 200 mg dose, see SmPC for Tremfya 200 mg solution for injection.
Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.
Special populations
Elderly
No dose adjustment is required (see section 5.2).
There is limited information in patients aged ≥65 years and very limited information in patients aged ≥75 years (see section 5.2).
Renal or hepatic impairment
Tremfya has not been studied in these patient populations. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies, and no dose adjustments are considered necessary. For further information on elimination of guselkumab, see section 5.2.
Paediatric population
The safety and efficacy of Tremfya in patients less than 18 years with ulcerative colitis, Crohn’s disease and psoriatic arthritis and in patients less than 6 years with psoriasis have not been established.
No data are available. Tremfya 100 mg solution for injection in pre-filled pens are not recommended for use in children below 18 years due to insufficient data on safety and efficacy. Currently available data with other presentations are described in sections 4.8, 5.1 and 5.2.
Method of administration
Subcutaneous use only. Sites for injection include the abdomen, thigh and back of the upper arm.
Tremfya should not be injected into areas where the skin is tender, bruised, red, hard, thick or scaly. If possible, areas of the skin that show psoriasis should be avoided as injection sites.
After proper training in subcutaneous injection technique, patients may inject Tremfya if a physician determines that this is appropriate. However, the physician should ensure appropriate medical follow-up of patients. Patients should be instructed to inject the full amount of solution according to the ‘Instructions for use’ provided in the carton.
For instructions on preparation of the medicinal product before administration, see section 6.6.

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which it is indicated.

Posology
Ulcerative colitis
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg concentrate for solution for infusion.
or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8.
After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 100 mg dose, see SmPC for Tremfya 100 mg solution for injection.
Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Crohn’s disease
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4, and Week 8. See SmPC for Tremfya 200 mg concentrate for solution for infusion.
or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8.
After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose regimen of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 100 mg dose, see SmPC for Tremfya 100 mg solution for injection.
Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.
Special populations
Elderly
No dose adjustment is required (see section 5.2).
There is limited information in patients aged ≥65 years and very limited information in patients aged ≥75 years (see section 5.2).

Renal or hepatic impairment
Tremfya has not been studied in these patient populations. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies, and no dose adjustments are considered necessary. For further information on elimination of guselkumab, see section 5.2.
Paediatric population
The safety and efficacy of Tremfya in children and adolescents with ulcerative colitis and Crohn’s disease below the age of 18 years have not been established. No data are available.
Method of administration
Subcutaneous use only. Sites for injection include the abdomen, thigh and back of the upper arm.
Tremfya should not be injected into areas where the skin is tender, bruised, red, hard, thick or scaly.
After proper training in subcutaneous injection technique, patients may inject Tremfya if a physician determines that this is appropriate. However, the physician should ensure appropriate medical follow-up of patients. Patients should be instructed to inject the full amount of solution according to the ‘Instructions for use’ provided in the carton.
For instructions on preparation of the medicinal product before administration, see section 6.6.

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which it is indicated.
Guselkumab 200 mg concentrate for solution for infusion should only be used for induction dose.
Posology
Ulcerative colitis
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4 and Week 8.

or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg solution for injection.
After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). See SmPC for Tremfya 100 mg solution for injection and 200 mg solution for injection.
Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Crohn’s disease
Either of the following two induction dose regimens are recommended:

200 mg administered by intravenous infusion at Week 0, Week 4, and Week 8.
or

400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg solution for injection.
After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose regimen of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). See SmPC for Tremfya 100 mg solution for injection and 200 mg solution for injection.
Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. In patients who have responded to treatment with guselkumab, corticosteroids may be reduced or discontinued in accordance with standard of care.
Consideration should be given to discontinuing treatment in patients who have shown no evidence of therapeutic benefit after 24 weeks of treatment.
Missed dose
If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should be resumed at the regular scheduled time.
Special populations
Elderly
No dose adjustment is required (see section 5.2).
There is limited information in patients aged ≥65 years and very limited information in patients aged ≥75 years (see section 5.2).
Renal or hepatic impairment
Tremfya has not been studied in these patient populations. These conditions are generally not expected to have any significant impact on the pharmacokinetics of monoclonal antibodies, and no dose adjustments are considered necessary. For further information on elimination of guselkumab, see section 5.2.

Paediatric population
The safety and efficacy of Tremfya in children and adolescents with ulcerative colitis and Crohn’s disease below the age of 18 years have not been established. No data are available.
Method of administration
Tremfya 200 mg concentrate for solution for infusion is for intravenous use only. It should be administered over a period of at least one hour. Each vial is for single use only. For instructions on dilution of the medicinal product before administration, see section 6.6.

Serious hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important active infections (e.g. active tuberculosis, see section 4.4).

Serious hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important active infections (e.g., active tuberculosis, see section 4.4).

Summary of the safety profile
The most common adverse reaction was respiratory tract infections (approximately 8% of patients in ulcerative colitis studies, 11% of patients in the Crohn’s disease studies, and 15% of patients in the psoriasis and psoriatic arthritis clinical studies).

The overall safety profile in patients treated with Tremfya is similar for patients with psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease.
Tabulated list of adverse reactions
Table 2 provides a list of adverse reactions from psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease clinical studies as well as adverse reactions reported from post-marketing experience.
The adverse reactions are classified by MedDRA System Organ Class and frequency, using the following convention: very common (≥1/10), common (≥1/100 to < 1/10), uncommon (≥1/1 000 to < 1/100), rare (≥1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2:
List of adverse reactions
System Organ Class
Frequency
Adverse reactions
Infections and infestations
Very common
Respiratory tract infections
Uncommon
Herpes simplex infections
Uncommon
Tinea infections
Uncommon
Gastroenteritis
Immune system disorders
Rare
Hypersensitivity
Rare
Anaphylaxis
Nervous system disorders
Common
Headache
Gastrointestinal disorders
Common
Diarrhoea
Skin and subcutaneous tissue disorders
Common
Rash
Uncommon
Urticaria
Musculoskeletal and connective tissue disorders
Common
Arthralgia
General disorders and administration site conditions
Common
Injection site reactions
Investigations
Common
Transaminases increased
Uncommon
Neutrophil count decreased
Description of selected adverse reactions
Transaminases increased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, liver function test abnormal, hypertransaminasaemia) were reported more frequently in the guselkumab treated groups (8.6% in the 100 mg subcutaneous q4w group and 8.3% in the 100 mg subcutaneous q8w group) than in the placebo group (4.6%). Through 1- year, adverse reactions of increased transaminases (as above) were reported in 12.9% of patients in the q4w group and 11.7% of patients in the q8w group.
Based on laboratory assessments, most transaminase increases (ALT and AST) were ≤3 x upper limit of normal (ULN). Transaminase increases from > 3 to ≤5 x ULN and > 5 x ULN were low in frequency, occurring more often in the guselkumab q4w group compared with the guselkumab q8w group (Table 3). A similar pattern of frequency by severity and by treatment group was observed through the end of the 2-year Phase III psoriatic arthritis clinical study.

Table 3:
Frequency of patients with transaminase increases post-baseline in two Phase III psoriatic arthritis clinical studies Through Week 24a Through 1 yearb Placebo N=370c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c ALT >1 to ≤3 x ULN 30.0% 28.2% 35.0% 33.5% 41.2% >3 to ≤ 5 x ULN 1.4% 1.1% 2.7% 1.6% 4.6% >5 x ULN 0.8% 0.8% 1.1% 1.1% 1.1% AST >1 to ≤3 x ULN 20.0% 18.8% 21.6% 22.8% 27.8% >3 to ≤ 5 x ULN 0.5% 1.6% 1.6% 2.9% 3.8% >5 x ULN 1.1% 0.5% 1.6% 0.5% 1.6% a placebo-controlled period.
b patients randomised to placebo at baseline and crossed over to guselkumab are not included.
c number of patients with at least one post-baseline assessment for the specific laboratory test within the time period.
In the psoriasis clinical studies, through 1 year, the frequency of transaminase increases (ALT and AST) for the guselkumab q8w dose was similar to that observed for the guselkumab q8w dose in the psoriatic arthritis clinical studies. Through 5 years, the incidence of transaminase elevation did not increase by year of guselkumab treatment. Most transaminase increases were ≤3 x ULN.
In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo-controlled induction period (Week 0-12), adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, and liver function test increased) were reported more frequently in the guselkumab treated groups (1.7% of patients) than in the placebo group (0.6% of patients). In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, hepatic function abnormal, and liver function test increased) were reported in 3.4% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 4.1% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 2.4% in the placebo group.
Based on laboratory assessments in pooled Phase II and Phase III Crohn’s disease clinical studies, the frequency of ALT or AST elevations were lower than those observed in psoriatic arthritis Phase III clinical studies. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo- controlled period (Week 12), ALT (< 1% of patients) and AST (< 1% of patients) elevations ≥3x ULN were reported in guselkumab treated patients. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, ALT and/or AST elevations ≥3x ULN were reported in 2.7% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 2.6% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 1.9% in the placebo group. In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
Neutrophil count decreased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, the adverse reaction of decreased neutrophil count was reported more frequently in the guselkumab treated group (0.9%) than in the placebo group (0%). Through 1 year, the adverse reaction of decreased neutrophil count was reported in 0.9% of patients treated with guselkumab. In most cases, the decrease in blood neutrophil count was mild, transient, not associated with infection and did not lead to discontinuation of treatment.

Gastroenteritis
In two Phase III psoriasis clinical studies through the placebo-controlled period, gastroenteritis occurred more frequently in the guselkumab treated group (1.1%) than in the placebo group (0.7%).
Through Week 264, 5.8% of all guselkumab treated patients reported gastroenteritis. Adverse reactions of gastroenteritis were non-serious and did not lead to discontinuation of guselkumab through Week 264. Gastroenteritis rates observed in psoriatic arthritis clinical studies through the placebo-controlled period were similar to those observed in the psoriasis clinical studies.
Injection site reactions
In two Phase III psoriasis clinical studies through Week 48, 0.7% of guselkumab injections and 0.3% of placebo injections were associated with injection site reactions. Through Week 264, 0.4% of guselkumab injections were associated with injection site reactions. Injection site reactions were generally mild to moderate in severity; none were serious, and one led to discontinuation of guselkumab.
In two Phase III psoriatic arthritis clinical studies through Week 24, the number of patients that reported 1 or more injection site reactions was low and slightly higher in the guselkumab groups than in the placebo group; 5 (1.3%) patients in the guselkumab q8w group, 4 (1.1%) patients in the guselkumab q4w group, and 1 (0.3%) patient in the placebo group. One patient discontinued guselkumab due to an injection site reaction during the placebo-controlled period of the psoriatic arthritis clinical studies. Through 1 year, the proportion of patients reporting 1 or more injection site reactions was 1.6% and 2.4% in the guselkumab q8w and q4w groups, respectively. Overall, the rate of injections associated with injection site reactions observed in psoriatic arthritis clinical studies through the placebo-controlled period was similar to rates observed in the psoriasis clinical studies.
In the Phase III ulcerative colitis maintenance clinical study through Week 44, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7.9% (2.5% of injections) in the guselkumab 200 mg subcutaneous q4w group (guselkumab 200 mg was administered as two 100 mg injections in the Phase III ulcerative colitis maintenance clinical study) and no injection site reactions in the guselkumab 100 mg subcutaneous q8w group. Most injection site reactions were mild and none were serious.
In Phase II and Phase III Crohn’s disease clinical studies through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 4.1% (0.8% of injections) in the treatment group which received guselkumab 200 mg intravenous induction followed by 200 mg subcutaneous q4w, and 1.4% (0.6% of injections) of patients in the guselkumab 200 mg intravenous induction followed by 100 mg subcutaneous q8w group. Overall injection site reactions were mild;
none were serious.
In a Phase III Crohn’s disease clinical study through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7% (1.3% of injections) in the treatment group which received 400 mg subcutaneous induction followed by 200 mg subcutaneous q4w and 4.3% (0.7% of injections) of patients in the 400 mg guselkumab subcutaneous induction followed by 100 mg subcutaneous q8w group. Most injection site reactions were mild; none were serious.
Immunogenicity
The immunogenicity of guselkumab was evaluated using a sensitive and drug-tolerant immunoassay.
In pooled Phase II and Phase III analyses in patients with psoriasis and psoriatic arthritis, 5% (n=145) of patients treated with guselkumab developed antidrug antibodies in up to 52 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 8% (n=12) had antibodies that were classified as neutralising, which equates to 0.4% of all patients treated with guselkumab. In pooled Phase III analyses in patients with psoriasis, approximately 15% of patients treated with guselkumab developed antidrug antibodies in up to 264 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 5% had antibodies that were classified as neutralising, which equates to 0.76% of all patients treated with guselkumab. Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.

In the Phase III paediatric study, 18% (n=21) of paediatric psoriasis patients treated with guselkumab developed antidrug antibodies in up to week 44. Of the patients who developed antidrug antibodies, none had antibodies that were classified as neutralising. Antibodies to guselkumab were not associated with changes in pharmacokinetics, clinical efficacy or development of injection site reactions.
However, the number of patients who were positive for antibodies to guselkumab is too small for definitive conclusions about the impact on efficacy and safety of guselkumab.
In pooled Phase II and Phase III analyses in patients with ulcerative colitis, approximately 12% (n=58) of patients treated with guselkumab for up to 56 weeks developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 16% (n=9) had antibodies that were classified as neutralising, which equates to 2% of all patients treated with guselkumab. Antidrug antibodies were not associated with lower efficacy or the development of injection site reactions.
In pooled Phase II and Phase III analyses up to Week 48 in patients with Crohn’s disease who were treated with intravenous induction followed by subcutaneous maintenance dose regimen, approximately 5% (n=30) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 7% (n=2) had antibodies that were classified as neutralising antibodies, which equates to 0.3% of guselkumab treated patients. In a Phase III analysis up to Week 48 in patients with Crohn’s disease who were treated with subcutaneous induction followed by subcutaneous maintenance dose regimen, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of these patients, 13% (n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients.
Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
Paediatric population
Plaque psoriasis
The safety of guselkumab was assessed in a Phase III placebo- and active-controlled study in paediatric patients with moderate to severe plaque psoriasis. This clinical study evaluated safety for up to 52 weeks in 120 patients 6 to 17 years of age. The safety profile for guselkumab subcutaneous injection using the 45 mg/0.45 mL pre-filled pen or the 100 mg pre-filled syringe in paediatric patients 6 to 17 years was consistent with the safety profile reported in the adult plaque psoriasis studies (see section 4.2).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Summary of the safety profile
The most common adverse reaction was respiratory tract infections (approximately 8% of patients in ulcerative colitis studies, 11% of patients in the Crohn’s disease studies, and 15% of patients in the psoriasis and psoriatic arthritis clinical studies).
The overall safety profile in patients treated with Tremfya is similar for patients with psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease.
Tabulated list of adverse reactions
Table 1 provides a list of adverse reactions from psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease clinical studies as well as adverse reactions reported from post-marketing experience.
The adverse reactions are classified by MedDRA System Organ Class and frequency, using the following convention: very common (≥1/10), common (≥1/100 to < 1/10), uncommon (≥1/1 000 to < 1/100), rare (≥1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 1:
List of adverse reactions
System Organ Class
Frequency
Adverse reactions
Infections and infestations
Very common
Respiratory tract infections
Uncommon
Herpes simplex infections
Uncommon
Tinea infections
Uncommon
Gastroenteritis
Immune system disorders
Rare
Hypersensitivity
Rare
Anaphylaxis
Nervous system disorders
Common
Headache
Gastrointestinal disorders
Common
Diarrhoea
Skin and subcutaneous tissue disorders
Common
Rash
Uncommon
Urticaria
Musculoskeletal and connective tissue disorders
Common
Arthralgia
General disorders and administration site conditions
Common
Injection site reactions
Investigations
Common
Transaminases increased
Uncommon
Neutrophil count decreased

Description of selected adverse reactions
Transaminases increased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, liver function test abnormal, hypertransaminasaemia) were reported more frequently in the guselkumab treated groups (8.6% in the 100 mg subcutaneous q4w group and 8.3% in the 100 mg subcutaneous q8w group) than in the placebo group (4.6%). Through 1-year, adverse reactions of increased transaminases (as above) were reported in 12.9% of patients in the q4w group and 11.7% of patients in the q8w group.
Based on laboratory assessments, most transaminase increases (ALT and AST) were ≤3 x upper limit of normal (ULN). Transaminase increases from > 3 to ≤5 x ULN and > 5 x ULN were low in frequency, occurring more often in the guselkumab q4w group compared with the guselkumab q8w group (Table 2). A similar pattern of frequency by severity and by treatment group was observed through the end of the 2-year Phase III psoriatic arthritis clinical study.
Table 2:
Frequency of patients with transaminase increases post-baseline in two Phase III psoriatic arthritis clinical studies Through Week 24a Through 1 yearb Placebo N=370c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c ALT >1 to ≤3 x ULN 30.0% 28.2% 35.0% 33.5% 41.2% >3 to ≤5 x ULN 1.4% 1.1% 2.7% 1.6% 4.6% >5 x ULN 0.8% 0.8% 1.1% 1.1% 1.1% AST >1 to ≤3 x ULN 20.0% 18.8% 21.6% 22.8% 27.8% >3 to ≤5 x ULN 0.5% 1.6% 1.6% 2.9% 3.8% >5 x ULN 1.1% 0.5% 1.6% 0.5% 1.6% a placebo-controlled period.
b patients randomised to placebo at baseline and crossed over to guselkumab are not included.
c number of patients with at least one post-baseline assessment for the specific laboratory test within the time period.
In the psoriasis clinical studies, through 1 year, the frequency of transaminase increases (ALT and AST) for the guselkumab q8w dose was similar to that observed for the guselkumab q8w dose in the psoriatic arthritis clinical studies. Through 5 years, the incidence of transaminase elevation did not increase by year of guselkumab treatment. Most transaminase increases were ≤3 x ULN.
In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo-controlled induction period (Week 0-12), adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, and liver function test increased) were reported more frequently in the guselkumab treated groups (1.7% of patients) than in the placebo group (0.6% of patients). In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, hepatic function abnormal, and liver function test increased) were reported in 3.4% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 4.1% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 2.4% in the placebo group.
Based on laboratory assessments in pooled Phase II and Phase III Crohn’s disease clinical studies, the frequency of ALT or AST elevations were lower than those observed in psoriatic arthritis Phase III clinical studies. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo-

controlled period (Week 12), ALT (< 1% of patients) and AST (< 1% of patients) elevations ≥3x ULN were reported in guselkumab treated patients. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, ALT and/or AST elevations ≥3x ULN were reported in 2.7% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 2.6% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 1.9% in the placebo group. In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
Neutrophil count decreased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, the adverse reaction of decreased neutrophil count was reported more frequently in the guselkumab treated group (0.9%) than in the placebo group (0%). Through 1 year, the adverse reaction of decreased neutrophil count was reported in 0.9% of patients treated with guselkumab. In most cases, the decrease in blood neutrophil count was mild, transient, not associated with infection and did not lead to discontinuation of treatment.
Gastroenteritis
In two Phase III psoriasis clinical studies through the placebo-controlled period, gastroenteritis occurred more frequently in the guselkumab treated group (1.1%) than in the placebo group (0.7%).
Through Week 264, 5.8% of all guselkumab treated patients reported gastroenteritis. Adverse reactions of gastroenteritis were non-serious and did not lead to discontinuation of guselkumab through Week 264. Gastroenteritis rates observed in psoriatic arthritis clinical studies through the placebo-controlled period were similar to those observed in the psoriasis clinical studies.
Injection site reactions
In two Phase III psoriasis clinical studies through Week 48, 0.7% of guselkumab injections and 0.3% of placebo injections were associated with injection site reactions. Through Week 264, 0.4% of guselkumab injections were associated with injection site reactions. Injection site reactions were generally mild to moderate in severity; none were serious, and one led to discontinuation of guselkumab.
In two Phase III psoriatic arthritis clinical studies through Week 24, the number of patients that reported 1 or more injection site reactions was low and slightly higher in the guselkumab groups than in the placebo group; 5 (1.3%) patients in the guselkumab q8w group, 4 (1.1%) patients in the guselkumab q4w group, and 1 (0.3%) patient in the placebo group. One patient discontinued guselkumab due to an injection site reaction during the placebo-controlled period of the psoriatic arthritis clinical studies. Through 1 year, the proportion of patients reporting 1 or more injection site reactions was 1.6% and 2.4% in the guselkumab q8w and q4w groups respectively. Overall, the rate of injections associated with injection site reactions observed in psoriatic arthritis clinical studies through the placebo-controlled period was similar to rates observed in the psoriasis clinical studies.
In the Phase III ulcerative colitis maintenance clinical study through Week 44, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7.9% (2.5% of injections) in the guselkumab 200 mg subcutaneous q4w group (guselkumab 200 mg was administered as two 100 mg injections in the Phase III ulcerative colitis maintenance clinical study) and no injection site reactions in the guselkumab 100 mg subcutaneous q8w group. Most injection site reactions were mild and none were serious.
In Phase II and Phase III Crohn’s disease clinical studies through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 4.1% (0.8% of injections) in the treatment group which received guselkumab 200 mg intravenous induction followed by 200 mg subcutaneous q4w, and 1.4% (0.6% of injections) of patients in the guselkumab 200 mg intravenous induction followed by 100 mg subcutaneous q8w group. Overall injection site reactions were mild;
none were serious.
In a Phase III Crohn’s disease clinical study through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7% (1.3% of injections) in the treatment group

which received 400 mg subcutaneous induction followed by 200 mg subcutaneous q4w and 4.3% (0.7% of injections) of patients in the 400 mg guselkumab subcutaneous induction followed by 100 mg subcutaneous q8w group. Most injection site reactions were mild; none were serious.
Immunogenicity
The immunogenicity of guselkumab was evaluated using a sensitive and drug-tolerant immunoassay.
In pooled Phase II and Phase III analyses in patients with psoriasis and psoriatic arthritis, 5% (n=145) of patients treated with guselkumab developed antidrug antibodies in up to 52 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 8% (n=12) had antibodies that were classified as neutralising, which equates to 0.4% of all patients treated with guselkumab. In pooled Phase III analyses in patients with psoriasis, approximately 15% of patients treated with guselkumab developed antidrug antibodies in up to 264 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 5% had antibodies that were classified as neutralising, which equates to 0.76% of all patients treated with guselkumab. Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
In the Phase III paediatric study, 18% (n=21) of paediatric psoriasis patients treated with guselkumab developed antidrug antibodies in up to Week 44. Of the patients who developed antidrug antibodies, none had antibodies that were classified as neutralising. Antibodies to guselkumab were not associated with changes in pharmacokinetics, clinical efficacy or development of injection site reactions.
However, the number of patients who were positive for antibodies to guselkumab is too small for definitive conclusions about the impact on efficacy and safety of guselkumab.
In pooled Phase II and Phase III analyses in patients with ulcerative colitis who were treated with intravenous induction followed by subcutaneous maintenance, approximately 12% (n=58) of patients treated with guselkumab for up to 56 weeks developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 16% (n=9) had antibodies that were classified as neutralising, which equates to 2% of all patients treated with guselkumab. In a Phase III analysis up to Week 24 in patients with ulcerative colitis who were treated with subcutaneous induction followed by subcutaneous maintenance, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, 13% (n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients.
Antidrug antibodies were not associated with lower efficacy or the development of injection site reactions.
In pooled Phase II and Phase III analyses up to Week 48 in patients with Crohn’s disease who were treated with intravenous induction followed by subcutaneous maintenance dose regimen, approximately 5% (n=30) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 7% (n=2) had antibodies that were classified as neutralising antibodies, which equates to 0.3% of guselkumab treated patients. In a Phase III analysis up to Week 48 in patients with Crohn’s disease who were treated with subcutaneous induction followed by subcutaneous maintenance dose regimen, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of these patients, 13% (n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients.
Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
Paediatric population
Plaque psoriasis
The safety of guselkumab was assessed in a Phase III placebo- and active-controlled study in paediatric patients with moderate to severe plaque psoriasis. This clinical study evaluated safety for up to 52 weeks in 120 patients 6 to 17 years of age. The safety profile for guselkumab subcutaneous injection using the 45 mg/0.45 mL pre-filled pen or the 100 mg pre-filled syringe in paediatric patients 6 to 17 years was consistent with the safety profile reported in the adult plaque psoriasis studies (see section 4.2).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Summary of the safety profile
The most common adverse reaction was respiratory tract infections (approximately 8% of patients in ulcerative colitis studies, 11% of patients in the Crohn’s disease studies, and 15% of patients in the psoriasis and psoriatic arthritis clinical studies).
The overall safety profile in patients treated with Tremfya is similar for patients with psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease.
Tabulated list of adverse reactions
Table 1 provides a list of adverse reactions from psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease clinical studies as well as adverse reactions reported from post-marketing experience.
The adverse reactions are classified by MedDRA System Organ Class and frequency, using the following convention: very common (≥1/10), common (≥1/100 to < 1/10), uncommon (≥1/1 000 to < 1/100), rare (≥1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 1:
List of adverse reactions
System Organ Class
Frequency
Adverse reactions
Infections and infestations
Very common
Respiratory tract infections
Uncommon
Herpes simplex infections
Uncommon
Tinea infections
Uncommon
Gastroenteritis
Immune system disorders
Rare
Hypersensitivity
Rare
Anaphylaxis
Nervous system disorders
Common
Headache
Gastrointestinal disorders
Common
Diarrhoea
Skin and subcutaneous tissue disorders
Common
Rash
Uncommon
Urticaria
Musculoskeletal and connective tissue disorders
Common
Arthralgia
General disorders and administration site conditions
Common
Injection site reactions
Investigations
Common
Transaminases increased
Uncommon
Neutrophil count decreased
Description of selected adverse reactions
Transaminases increased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, liver function test abnormal, hypertransaminasaemia) were reported more frequently in the guselkumab treated groups (8.6% in the 100 mg subcutaneous q4w group and 8.3% in the 100 mg subcutaneous q8w group) than in the placebo group (4.6%). Through 1-year, adverse reactions of increased transaminases (as above) were reported in 12.9% of patients in the q4w group and 11.7% of patients in the q8w group.

Based on laboratory assessments, most transaminase increases (ALT and AST) were ≤3 x upper limit of normal (ULN). Transaminase increases from > 3 to ≤5 x ULN and > 5 x ULN were low in frequency, occurring more often in the guselkumab q4w group compared with the guselkumab q8w group (Table 2). A similar pattern of frequency by severity and by treatment group was observed through the end of the 2-year Phase III psoriatic arthritis clinical study.
Table 2:
Frequency of patients with transaminase increases post-baseline in two Phase III psoriatic arthritis clinical studies Through Week 24a Through 1 yearb Placebo N=370c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c ALT >1 to ≤3 x ULN 30.0% 28.2% 35.0% 33.5% 41.2% >3 to ≤5 x ULN 1.4% 1.1% 2.7% 1.6% 4.6% >5 x ULN 0.8% 0.8% 1.1% 1.1% 1.1% AST >1 to ≤3 x ULN 20.0% 18.8% 21.6% 22.8% 27.8% >3 to ≤5 x ULN 0.5% 1.6% 1.6% 2.9% 3.8% >5 x ULN 1.1% 0.5% 1.6% 0.5% 1.6% a placebo-controlled period.
b patients randomised to placebo at baseline and crossed over to guselkumab are not included.
c number of patients with at least one post-baseline assessment for the specific laboratory test within the time period.
In the psoriasis clinical studies, through 1 year, the frequency of transaminase increases (ALT and AST) for the guselkumab q8w dose was similar to that observed for the guselkumab q8w dose in the psoriatic arthritis clinical studies. Through 5 years, the incidence of transaminase elevation did not increase by year of guselkumab treatment. Most transaminase increases were ≤3 x ULN.
In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo-controlled induction period (Week 0-12), adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, and liver function test increased) were reported more frequently in the guselkumab treated groups (1.7% of patients) than in the placebo group (0.6% of patients). In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, hepatic function abnormal, and liver function test increased) were reported in 3.4% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 4.1% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 2.4% in the placebo group.
Based on laboratory assessments in pooled Phase II and Phase III Crohn’s disease clinical studies, the frequency of ALT or AST elevations were lower than those observed in psoriatic arthritis Phase III clinical studies. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo- controlled period (Week 12), ALT (< 1% of patients) and AST (< 1% of patients) elevations ≥3x ULN were reported in guselkumab treated patients. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, ALT and/or AST elevations ≥3x ULN were reported in 2.7% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 2.6% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 1.9% in the placebo group. In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
Neutrophil count decreased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, the adverse reaction of decreased neutrophil count was reported more frequently in the guselkumab treated group

(0.9%) than in the placebo group (0%). Through 1 year, the adverse reaction of decreased neutrophil count was reported in 0.9% of patients treated with guselkumab. In most cases, the decrease in blood neutrophil count was mild, transient, not associated with infection and did not lead to discontinuation of treatment.
Gastroenteritis
In two Phase III psoriasis clinical studies through the placebo-controlled period, gastroenteritis occurred more frequently in the guselkumab treated group (1.1%) than in the placebo group (0.7%).
Through Week 264, 5.8% of all guselkumab treated patients reported gastroenteritis. Adverse reactions of gastroenteritis were non-serious and did not lead to discontinuation of guselkumab through Week 264. Gastroenteritis rates observed in psoriatic arthritis clinical studies through the placebo-controlled period were similar to those observed in the psoriasis clinical studies.
Injection site reactions
In two Phase III psoriasis clinical studies through Week 48, 0.7% of guselkumab injections and 0.3% of placebo injections were associated with injection site reactions. Through Week 264, 0.4% of guselkumab injections were associated with injection site reactions. Injection site reactions were generally mild to moderate in severity; none were serious, and one led to discontinuation of guselkumab.
In two Phase III psoriatic arthritis clinical studies through Week 24, the number of patients that reported 1 or more injection site reactions was low and slightly higher in the guselkumab groups than in the placebo group; 5 (1.3%) patients in the guselkumab q8w group, 4 (1.1%) patients in the guselkumab q4w group, and 1 (0.3%) patient in the placebo group. One patient discontinued guselkumab due to an injection site reaction during the placebo-controlled period of the psoriatic arthritis clinical studies. Through 1 year, the proportion of patients reporting 1 or more injection site reactions was 1.6% and 2.4% in the guselkumab q8w and q4w groups respectively. Overall, the rate of injections associated with injection site reactions observed in psoriatic arthritis clinical studies through the placebo-controlled period was similar to rates observed in the psoriasis clinical studies.
In the Phase III ulcerative colitis maintenance clinical study through Week 44, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7.9% (2.5% of injections) in the guselkumab 200 mg subcutaneous q4w group (guselkumab 200 mg was administered as two 100 mg injections in the Phase III ulcerative colitis maintenance clinical study) and no injection site reactions in the guselkumab 100 mg subcutaneous q8w group. Most injection site reactions were mild and none were serious.
In Phase II and Phase III Crohn’s disease clinical studies through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 4.1% (0.8% of injections) in the treatment group which received guselkumab 200 mg intravenous induction followed by 200 mg subcutaneous q4w, and 1.4% (0.6% of injections) of patients in the guselkumab 200 mg intravenous induction followed by 100 mg subcutaneous q8w group. Overall injection site reactions were mild;
none were serious.
In a Phase III Crohn’s disease clinical study through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7% (1.3% of injections) in the treatment group which received 400 mg subcutaneous induction followed by 200 mg subcutaneous q4w and 4.3% (0.7% of injections) of patients in the 400 mg guselkumab subcutaneous induction followed by 100 mg subcutaneous q8w group. Most injection site reactions were mild; none were serious.
Immunogenicity
The immunogenicity of guselkumab was evaluated using a sensitive and drug-tolerant immunoassay.
In pooled Phase II and Phase III analyses in patients with psoriasis and psoriatic arthritis, 5% (n=145) of patients treated with guselkumab developed antidrug antibodies in up to 52 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 8% (n=12) had antibodies that were classified as neutralising, which equates to 0.4% of all patients treated with guselkumab. In pooled

Phase III analyses in patients with psoriasis, approximately 15% of patients treated with guselkumab developed antidrug antibodies in up to 264 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 5% had antibodies that were classified as neutralising, which equates to 0.76% of all patients treated with guselkumab. Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
In pooled Phase II and Phase III analyses in patients with ulcerative colitis who were treated with intravenous induction followed by subcutaneous maintenance, approximately 12% (n=58) of patients treated with guselkumab for up to 56 weeks developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 16% (n=9) had antibodies that were classified as neutralising, which equates to 2% of all patients treated with guselkumab. In a Phase III analysis up to Week 24 in patients with ulcerative colitis who were treated with subcutaneous induction followed by subcutaneous maintenance, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, 13% (n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients.
Antidrug antibodies were not associated with lower efficacy or the development of injection site reactions.
In pooled Phase II and Phase III analyses up to Week 48 in patients with Crohn’s disease who were treated with intravenous induction followed by subcutaneous maintenance dose regimen, approximately 5% (n=30) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 7% (n=2) had antibodies that were classified as neutralising antibodies, which equates to 0.3% of guselkumab treated patients. In a Phase III analysis up to Week 48 in patients with Crohn’s disease who were treated with subcutaneous induction followed by subcutaneous maintenance dose regimen, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of these patients, 13% (n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients.
Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
Paediatric population
Plaque psoriasis
The safety of guselkumab was assessed in a Phase III placebo- and active-controlled study in paediatric patients with moderate to severe plaque psoriasis. This clinical study evaluated safety for up to 52 weeks in 120 patients 6 to 17 years of age. The safety profile for guselkumab subcutaneous injection using the 45 mg/0.45 mL pre-filled pen or the 100 mg pre-filled syringe in paediatric patients 6 to 17 years was consistent with the safety profile reported in the adult plaque psoriasis studies (see section 4.2).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Summary of the safety profile
The most common adverse reaction was respiratory tract infections (approximately 8% of patients in ulcerative colitis studies, 11% of patients in the Crohn’s disease studies, and 15% of patients in the psoriasis and psoriatic arthritis clinical studies).
The overall safety profile in patients treated with Tremfya is similar for patients with psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease.
Tabulated list of adverse reactions
Table 1 provides a list of adverse reactions from psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease clinical studies as well as adverse reactions reported from post-marketing experience.
The adverse reactions are classified by MedDRA System Organ Class and frequency, using the following convention: very common (≥1/10), common (≥1/100 to < 1/10), uncommon (≥1/1 000 to < 1/100), rare (≥1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1:
List of adverse reactions
System Organ Class
Frequency
Adverse reactions
Infections and infestations
Very common
Respiratory tract infections
Uncommon
Herpes simplex infections
Uncommon
Tinea infections
Uncommon
Gastroenteritis
Immune system disorders
Rare
Hypersensitivity
Rare
Anaphylaxis
Nervous system disorders
Common
Headache
Gastrointestinal disorders
Common
Diarrhoea
Skin and subcutaneous tissue disorders
Common
Rash
Uncommon
Urticaria
Musculoskeletal and connective tissue disorders
Common
Arthralgia
General disorders and administration site conditions
Common
Injection site reactions
Investigations
Common
Transaminases increased
Uncommon
Neutrophil count decreased
Description of selected adverse reactions
Transaminases increased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, liver function test abnormal, hypertransaminasaemia) were reported more frequently in the guselkumab treated groups (8.6% in the 100 mg subcutaneous q4w group and 8.3% in the 100 mg subcutaneous q8w group) than in the placebo group (4.6%). Through 1 year, adverse reactions of increased transaminases (as above) were reported in 12.9% of patients in the q4w group and 11.7% of patients in the q8w group.
Based on laboratory assessments, most transaminase increases (ALT and AST) were ≤3 x upper limit of normal (ULN). Transaminase increases from > 3 to ≤5 x ULN and > 5 x ULN were low in frequency, occurring more often in the guselkumab q4w group compared with the guselkumab q8w group (Table 2). A similar pattern of frequency by severity and by treatment group was observed through the end of the 2-year Phase III psoriatic arthritis clinical study.
Table 2:
Frequency of patients with transaminase increases post-baseline in two Phase III psoriatic arthritis clinical studies Through week 24a Through 1 yearb Placebo N=370c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c guselkumab 100 mg q8w N=373c guselkumab 100 mg q4w N=371c ALT > 1 to ≤3 x ULN 30.0% 28.2% 35.0% 33.5% 41.2% > 3 to ≤5 x ULN 1.4% 1.1% 2.7% 1.6% 4.6% > 5 x ULN 0.8% 0.8% 1.1% 1.1% 1.1% AST > 1 to ≤3 x ULN 20.0% 18.8% 21.6% 22.8% 27.8% > 3 to ≤5 x ULN 0.5% 1.6% 1.6% 2.9% 3.8% > 5 x ULN 1.1% 0.5% 1.6% 0.5% 1.6% a placebo-controlled period.
b patients randomised to placebo at baseline and crossed over to guselkumab are not included.
c number of patients with at least one post-baseline assessment for the specific laboratory test within the time period.
In the psoriasis clinical studies, through 1 year, the frequency of transaminase increases (ALT and AST) for the guselkumab q8w dose was similar to that observed for the guselkumab q8w dose in the

psoriatic arthritis clinical studies. Through 5 years, the incidence of transaminase elevation did not increase by year of guselkumab treatment. Most transaminase increases were ≤3 x ULN.
In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo-controlled induction period (Week 0-12), adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, and liver function test increased) were reported more frequently in the guselkumab treated groups (1.7% of patients) than in the placebo group (0.6% of patients). In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, adverse reactions of increased transaminases (includes ALT increased, AST increased, hepatic enzyme increased, transaminases increased, hepatic function abnormal, and liver function test increased) were reported in 3.4% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 4.1% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 2.4% in the placebo group.
Based on laboratory assessments in pooled Phase II and Phase III Crohn’s disease clinical studies, the frequency of ALT or AST elevations were lower than those observed in psoriatic arthritis Phase III clinical studies. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo- controlled period (Week 12), ALT (< 1% of patients) and AST (< 1% of patients) elevations ≥3x ULN were reported in guselkumab treated patients. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the reporting period of approximately one year, ALT and/or AST elevations ≥3x ULN were reported in 2.7% of patients in the guselkumab 200 mg subcutaneous q4w treatment group and 2.6% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to 1.9% in the placebo group. In most cases, the increase in transaminases was transient and did not lead to discontinuation of treatment.
Neutrophil count decreased
In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, the adverse reaction of decreased neutrophil count was reported more frequently in the guselkumab treated group (0.9%) than in the placebo group (0%). Through 1 year, the adverse reaction of decreased neutrophil count was reported in 0.9% of patients treated with guselkumab. In most cases, the decrease in blood neutrophil count was mild, transient, not associated with infection and did not lead to discontinuation of treatment.
Gastroenteritis
In two Phase III psoriasis clinical studies through the placebo-controlled period, gastroenteritis occurred more frequently in the guselkumab treated group (1.1%) than in the placebo group (0.7%).
Through Week 264, 5.8% of all guselkumab treated patients reported gastroenteritis. Adverse reactions of gastroenteritis were non-serious and did not lead to discontinuation of guselkumab through Week 264. Gastroenteritis rates observed in psoriatic arthritis clinical studies through the placebo-controlled period were similar to those observed in the psoriasis clinical studies.
Injection site reactions
In two Phase III psoriasis clinical studies through Week 48, 0.7% of guselkumab injections and 0.3% of placebo injections were associated with injection site reactions. Through Week 264, 0.4% of guselkumab injections were associated with injection site reactions. Injection site reactions were generally mild to moderate in severity; none were serious, and one led to discontinuation of guselkumab.
In two Phase III psoriatic arthritis clinical studies through Week 24, the number of patients that reported 1 or more injection site reactions was low and slightly higher in the guselkumab groups than in the placebo group; 5 (1.3%) patients in the guselkumab q8w group, 4 (1.1%) patients in the guselkumab q4w group, and 1 (0.3%) patient in the placebo group. One patient discontinued guselkumab due to an injection site reaction during the placebo-controlled period of the psoriatic arthritis clinical studies. Through 1 year, the proportion of patients reporting 1 or more injection site

reactions was 1.6% and 2.4% in the guselkumab q8w and q4w groups respectively. Overall, the rate of injections associated with injection site reactions observed in psoriatic arthritis clinical studies through the placebo-controlled period was similar to rates observed in the psoriasis clinical studies.
In the Phase III ulcerative colitis maintenance clinical study through Week 44, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7.9% (2.5% of injections) in the guselkumab 200 mg subcutaneous q4w group (guselkumab 200 mg was administered as two 100 mg injections in the Phase III ulcerative colitis maintenance clinical study) and no injection site reactions in the guselkumab 100 mg subcutaneous q8w group. Most injection site reactions were mild and none were serious.
In Phase II and Phase III Crohn’s disease clinical studies through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 4.1% (0.8% of injections) in the treatment group which received guselkumab 200 mg intravenous induction followed by 200 mg subcutaneous q4w, and 1.4% (0.6% of injections) of patients in the guselkumab 200 mg intravenous induction followed by 100 mg subcutaneous q8w group. Overall injection site reactions were mild;
none were serious.
In a Phase III Crohn’s disease clinical study through Week 48, the proportion of patients that reported 1 or more injection site reactions to guselkumab was 7% (1.3% of injections) in the treatment group which received 400 mg subcutaneous induction followed by 200 mg subcutaneous q4w and 4.3% (0.7% of injections) of patients in the 400 mg guselkumab subcutaneous induction followed by 100 mg subcutaneous q8w group. Most injection site reactions were mild; none were serious.
Immunogenicity
The immunogenicity of guselkumab was evaluated using a sensitive and drug-tolerant immunoassay.
In pooled Phase II and Phase III analyses in patients with psoriasis and psoriatic arthritis, 5% (n=145) of patients treated with guselkumab developed antidrug antibodies in up to 52 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 8% (n=12) had antibodies that were classified as neutralising, which equates to 0.4% of all patients treated with guselkumab. In pooled Phase III analyses in patients with psoriasis, approximately 15% of patients treated with guselkumab developed antidrug antibodies in up to 264 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 5% had antibodies that were classified as neutralising, which equates to 0.76% of all patients treated with guselkumab. Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
In pooled Phase II and Phase III analyses in patients with ulcerative colitis who were treated with intravenous induction followed by subcutaneous maintenance, approximately 12% (n=58) of patients treated with guselkumab for up to 56 weeks developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 16% (n=9) had antibodies that were classified as neutralising, which equates to 2% of all patients treated with guselkumab. In a Phase III analysis up to Week 24 in patients with ulcerative colitis who were treated with subcutaneous induction followed by subcutaneous maintenance, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, 13% (n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients.
Antidrug antibodies were not associated with lower efficacy or the development of injection site reactions.
In pooled Phase II and Phase III analyses up to Week 48 in patients with Crohn’s disease who were treated with intravenous induction followed by subcutaneous maintenance dose regimen, approximately 5% (n=30) of patients treated with guselkumab developed antidrug antibodies. Of the patients who developed antidrug antibodies, approximately 7% (n=2) had antibodies that were classified as neutralising antibodies, which equates to 0.3% of guselkumab treated patients.
In a Phase III analysis up to Week 48 in patients with Crohn’s disease who were treated with subcutaneous induction followed by subcutaneous maintenance dose regimen, approximately 9% (n=24) of patients treated with guselkumab developed antidrug antibodies. Of these patients, 13%

(n=3) had antibodies that were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients. Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infections
Guselkumab may increase the risk of infection. Treatment should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with guselkumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, the patient should be monitored closely and treatment should be discontinued until the infection resolves.
Pre-treatment evaluation for tuberculosis
Prior to initiating treatment, patients should be evaluated for tuberculosis (TB) infection. Patients receiving guselkumab should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.
Hypersensitivity
Serious hypersensitivity reactions, including anaphylaxis, have been reported in the post-marketing setting (see section 4.8). Some serious hypersensitivity reactions occurred several days after treatment with guselkumab, including cases with urticaria and dyspnoea. If a serious hypersensitivity reaction occurs, administration of guselkumab should be discontinued immediately and appropriate therapy initiated.
Hepatic transaminase elevations
In psoriatic arthritis clinical studies, an increased incidence of liver enzyme elevations was observed in patients treated with guselkumab q4w compared to patients treated with guselkumab q8w or placebo (see section 4.8).
Immunisations
Prior to initiating therapy, completion of all age-appropriate immunisations should be considered according to current immunisation guidelines. Live vaccines should not be used concurrently in patients treated with guselkumab. No data are available on the response to live or inactive vaccines.
Before live viral or live bacterial vaccination, treatment should be withheld for at least 12 weeks after the last dose and can be resumed at least 2 weeks after vaccination. Prescribers should consult the Summary of Product Characteristics of the specific vaccine for additional information and guidance on concomitant use of immunosuppressive agents post-vaccination.
Excipients with known effect
Polysorbate 80 content
This medicinal product contains 0.3 mg of polysorbate 80 (E433) in each pre-filled pen which is equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions.

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infections
Guselkumab may increase the risk of infection. Treatment should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with guselkumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, the patient should be monitored closely and treatment should be discontinued until the infection resolves.
Pre-treatment evaluation for tuberculosis
Prior to initiating treatment, patients should be evaluated for tuberculosis (TB) infection. Patients receiving guselkumab should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.
Hypersensitivity
Serious hypersensitivity reactions, including anaphylaxis, have been reported in the post-marketing setting (see section 4.8). Some serious hypersensitivity reactions occurred several days after treatment with guselkumab, including cases with urticaria and dyspnoea. If a serious hypersensitivity reaction occurs, administration of guselkumab should be discontinued immediately and appropriate therapy initiated.
Hepatic transaminase elevations
In psoriatic arthritis clinical studies, an increased incidence of liver enzyme elevations was observed in patients treated with guselkumab q4w compared to patients treated with guselkumab q8w or placebo (see section 4.8).
When prescribing guselkumab q4w in psoriatic arthritis, it is recommended to evaluate liver enzymes at baseline and thereafter according to routine patient management. If increases in alanine aminotransferase [ALT] or aspartate aminotransferase [AST] are observed and drug-induced liver injury is suspected, treatment should be temporarily interrupted until this diagnosis is excluded.

Immunisations
Prior to initiating therapy, completion of all appropriate immunisations should be considered according to current immunisation guidelines. Live vaccines should not be used concurrently in patients treated with guselkumab. No data are available on the response to live or inactive vaccines.
Before live viral or live bacterial vaccination, treatment should be withheld for at least 12 weeks after the last dose and can be resumed at least 2 weeks after vaccination. Prescribers should consult the Summary of Product Characteristics of the specific vaccine for additional information and guidance on concomitant use of immunosuppressive agents post-vaccination.
Excipients with known effect
Polysorbate 80 content
This medicinal product contains 0.5 mg of polysorbate 80 (E433) in each pre-filled syringe which is equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions.

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infections
Guselkumab may increase the risk of infection. Treatment should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with guselkumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, the patient should be monitored closely and treatment should be discontinued until the infection resolves.
Pre-treatment evaluation for tuberculosis
Prior to initiating treatment, patients should be evaluated for tuberculosis (TB) infection. Patients receiving guselkumab should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.
Hypersensitivity
Serious hypersensitivity reactions, including anaphylaxis, have been reported in the post-marketing setting (see section 4.8). Some serious hypersensitivity reactions occurred several days after treatment with guselkumab, including cases with urticaria and dyspnoea. If a serious hypersensitivity reaction occurs, administration of guselkumab should be discontinued immediately and appropriate therapy initiated.
Hepatic transaminase elevations
In psoriatic arthritis clinical studies, an increased incidence of liver enzyme elevations was observed in patients treated with guselkumab q4w compared to patients treated with guselkumab q8w or placebo (see section 4.8).
When prescribing guselkumab q4w in psoriatic arthritis, it is recommended to evaluate liver enzymes at baseline and thereafter according to routine patient management. If increases in alanine aminotransferase [ALT] or aspartate aminotransferase [AST] are observed and drug-induced liver injury is suspected, treatment should be temporarily interrupted until this diagnosis is excluded.
Immunisations
Prior to initiating therapy, completion of all appropriate immunisations should be considered according to current immunisation guidelines. Live vaccines should not be used concurrently in patients treated with guselkumab. No data are available on the response to live or inactive vaccines.
Before live viral or live bacterial vaccination, treatment should be withheld for at least 12 weeks after the last dose and can be resumed at least 2 weeks after vaccination. Prescribers should consult the Summary of Product Characteristics of the specific vaccine for additional information and guidance on concomitant use of immunosuppressive agents post-vaccination.

Excipients with known effect
Polysorbate 80 content
This medicinal product contains 0.5 mg of polysorbate 80 (E433) in each pre-filled pen which is equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions.

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infections
Guselkumab may increase the risk of infection. Treatment should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with guselkumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, the patient should be monitored closely and treatment should be discontinued until the infection resolves.
Pre-treatment evaluation for tuberculosis
Prior to initiating treatment, patients should be evaluated for tuberculosis (TB) infection. Patients receiving guselkumab should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.
Hypersensitivity
Serious hypersensitivity reactions, including anaphylaxis, have been reported in the post-marketing setting (see section 4.8). Some serious hypersensitivity reactions occurred several days after treatment

with guselkumab, including cases with urticaria and dyspnoea. If a serious hypersensitivity reaction occurs, administration of guselkumab should be discontinued immediately and appropriate therapy initiated.
Hepatic transaminase elevations
In psoriatic arthritis clinical studies, an increased incidence of liver enzyme elevations was observed in patients treated with guselkumab q4w compared to patients treated with guselkumab q8w or placebo (see section 4.8).
When prescribing guselkumab q4w in psoriatic arthritis, it is recommended to evaluate liver enzymes at baseline and thereafter according to routine patient management. If increases in alanine aminotransferase [ALT] or aspartate aminotransferase [AST] are observed and drug-induced liver injury is suspected, treatment should be temporarily interrupted until this diagnosis is excluded.
Immunisations
Prior to initiating therapy, completion of all appropriate immunisations should be considered according to current immunisation guidelines. Live vaccines should not be used concurrently in patients treated with guselkumab. No data are available on the response to live or inactive vaccines.
Before live viral or live bacterial vaccination, treatment should be withheld for at least 12 weeks after the last dose and can be resumed at least 2 weeks after vaccination. Prescribers should consult the Summary of Product Characteristics of the specific vaccine for additional information and guidance on concomitant use of immunosuppressive agents post-vaccination.
Excipients with known effect
Polysorbate 80 content
This medicinal product contains 1 mg of polysorbate 80 (E433) in each pre-filled syringe/pre-filled pen which is equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions.

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infections
Guselkumab may increase the risk of infection. Treatment should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Patients treated with guselkumab should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, the patient should be monitored closely and treatment should be discontinued until the infection resolves.
Pre-treatment evaluation for tuberculosis
Prior to initiating treatment, patients should be evaluated for tuberculosis (TB) infection. Patients receiving guselkumab should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.
Hypersensitivity
Serious hypersensitivity reactions, including anaphylaxis, have been reported in the post-marketing setting (see section 4.8). Some serious hypersensitivity reactions occurred several days after treatment with guselkumab, including cases with urticaria and dyspnoea. If a serious hypersensitivity reaction occurs, administration of guselkumab should be discontinued immediately and appropriate therapy initiated.
Hepatic transaminase elevations
In psoriatic arthritis clinical studies, an increased incidence of liver enzyme elevations was observed in patients treated with guselkumab q4w compared to patients treated with guselkumab q8w or placebo (see section 4.8).
When prescribing guselkumab q4w in psoriatic arthritis, it is recommended to evaluate liver enzymes at baseline and thereafter according to routine patient management. If increases in alanine

aminotransferase [ALT] or aspartate aminotransferase [AST] are observed and drug-induced liver injury is suspected, treatment should be temporarily interrupted until this diagnosis is excluded.
Immunisations
Prior to initiating therapy, completion of all appropriate immunisations should be considered according to current immunisation guidelines. Live vaccines should not be used concurrently in patients treated with guselkumab. No data are available on the response to live or inactive vaccines.
Before live viral or live bacterial vaccination, treatment should be withheld for at least 12 weeks after the last dose and can be resumed at least 2 weeks after vaccination. Prescribers should consult the Summary of Product Characteristics of the specific vaccine for additional information and guidance on concomitant use of immunosuppressive agents post-vaccination.
Excipients with known effect
Polysorbate 80 content
This medicinal product contains 10 mg of polysorbate 80 (E433) in each vial which is equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions.
Sodium content
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

Interactions with CYP450 substrates
In a Phase I study in patients with moderate to severe plaque psoriasis, changes in systemic exposures (Cmax and AUCinf) of midazolam, S-warfarin, omeprazole, dextromethorphan, and caffeine after a single dose of guselkumab were not clinically relevant, indicating that interactions between guselkumab and substrates of various CYP enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2) are unlikely. There is no need for dose adjustment when co-administering guselkumab and CYP450 substrates.
Concomitant immunosuppressive therapy or phototherapy
In psoriasis studies, the safety and efficacy of guselkumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated.

Interactions with CYP450 substrates
In a Phase I study in patients with moderate to severe plaque psoriasis, changes in systemic exposures (Cmax and AUCinf) of midazolam, S-warfarin, omeprazole, dextromethorphan, and caffeine after a single dose of guselkumab were not clinically relevant, indicating that interactions between guselkumab and substrates of various CYP enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2) are unlikely. There is no need for dose adjustment when co-administering guselkumab and CYP450 substrates.
Concomitant immunosuppressive therapy or phototherapy
In psoriasis studies, the safety and efficacy of guselkumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated. In psoriatic arthritis studies, concomitant MTX use did not appear to influence the safety or efficacy of guselkumab.
In ulcerative colitis and Crohn’s disease studies, concomitant use of immunomodulators (e.g., azathioprine [AZA], 6-mercaptopurine [6-MP]) or corticosteroids did not appear to influence the safety or efficacy of guselkumab.

Interactions with CYP450 substrates
In a Phase I study in patients with moderate to severe plaque psoriasis, changes in systemic exposures (Cmax and AUCinf) of midazolam, S-warfarin, omeprazole, dextromethorphan, and caffeine after a single dose of guselkumab were not clinically relevant, indicating that interactions between guselkumab and substrates of various CYP enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2) are unlikely. There is no need for dose adjustment when co-administering guselkumab and CYP450 substrates.
Concomitant immunosuppressive therapy or phototherapy
In psoriasis studies, the safety and efficacy of guselkumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated. In psoriatic arthritis studies, concomitant methotrexate (MTX) use did not appear to influence the safety or efficacy of guselkumab.
In ulcerative colitis and Crohn’s disease studies, concomitant use of immunomodulators (e.g., azathioprine [AZA], 6-mercaptopurine [6-MP]) or corticosteroids did not appear to influence the safety or efficacy of guselkumab.

Women of childbearing potential
Women of childbearing potential should use effective methods of contraception during treatment and for at least 12 weeks after treatment.
Pregnancy
There are limited data from the use of guselkumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Tremfya during pregnancy.
Breast-feeding
It is unknown whether guselkumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, and decrease to low concentrations soon afterwards;
consequently, a risk to the breast-fed infant during this period cannot be excluded. A decision should be made whether to discontinue breast-feeding or to abstain from Tremfya therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. See section 5.3 for information on the excretion of guselkumab in animal (cynomolgus monkey) milk.
Fertility
The effect of guselkumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Tremfya has no or negligible influence on the ability to drive and use machines.

Guselkumab intravenous doses up to 1 200 mg as well as subcutaneous doses up to 400 mg at a single dosing visit have been administered in clinical studies without dose-limiting toxicity. In the event of overdose, the patient must be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment must be administered immediately.
5.
PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC16.

Mechanism of action
Guselkumab is a human IgG1λ monoclonal antibody (mAb) that binds selectively to the interleukin 23 (IL-23) protein with high specificity and affinity through the antigen binding site. IL-23 is a cytokine that is involved in inflammatory and immune responses. By blocking IL-23 from binding to its receptor, guselkumab inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.
Levels of IL-23 are elevated in the skin of patients with plaque psoriasis. In in vitro models, guselkumab was shown to inhibit the bioactivity of IL-23 by blocking its interaction with cell surface IL-23 receptor, disrupting IL-23-mediated signalling, activation and cytokine cascades. Guselkumab exerts clinical effects in plaque psoriasis and psoriatic arthritis through blockade of the IL-23 cytokine pathway.
Myeloid cells expressing Fc-gamma receptor 1 (CD64) have been shown to be a predominant source of IL-23 in inflamed tissue in psoriasis. Guselkumab has demonstrated in vitro blocking of IL-23 and binding to CD64. These results indicate that guselkumab is able to neutralise IL-23 at the cellular source of inflammation.
Pharmacodynamic effects
In a Phase I study, treatment with guselkumab resulted in reduced expression of IL-23/Th17 pathway genes and psoriasis-associated gene expression profiles, as shown by analyses of mRNA obtained from lesional skin biopsies of patients with plaque psoriasis at Week 12 compared to baseline. In the same Phase I study, treatment with guselkumab resulted in improvement of histological measures of psoriasis at Week 12, including reductions in epidermal thickness and T-cell density. In addition, reduced serum IL-17A, IL-17F and IL-22 levels compared to placebo were observed in guselkumab treated patients in Phase II and Phase III plaque psoriasis studies. These results are consistent with the clinical benefit observed with guselkumab treatment in plaque psoriasis.
In psoriatic arthritis patients in Phase III studies, serum levels of acute phase proteins C-reactive protein, serum amyloid A, and IL-6, and Th17 effector cytokines IL-17A, IL-17F and IL-22 were elevated at baseline. Guselkumab decreased the levels of these proteins within 4 weeks of initiation of treatment. Guselkumab further reduced the levels of these proteins by Week 24 compared to baseline and also to placebo.
Clinical efficacy and safety
Adult plaque psoriasis
The efficacy and safety of guselkumab was assessed in three randomised, double-blind, active controlled Phase III studies in adult patients with moderate to severe plaque psoriasis, who were candidates for phototherapy or systemic therapy.
VOYAGE 1 and VOYAGE 2

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC16.
Mechanism of action
Guselkumab is a human IgG1λ monoclonal antibody (mAb) that binds selectively to the interleukin 23 (IL-23) protein with high specificity and affinity through the antigen binding site. IL-23 is a cytokine that is involved in inflammatory and immune responses. By blocking IL-23 from binding to its receptor, guselkumab inhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.
Levels of IL-23 are elevated in the skin of patients with plaque psoriasis. In patients with ulcerative colitis or Crohn’s disease, levels of IL-23 are elevated in the colon tissue. In in vitro models, guselkumab was shown to inhibit the bioactivity of IL-23 by blocking its interaction with cell surface IL-23 receptor, disrupting IL-23-mediated signalling, activation and cytokine cascades. Guselkumab exerts clinical effects in plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease through blockade of the IL-23 cytokine pathway.
Myeloid cells expressing Fc-gamma receptor 1 (CD64) have been shown to be a predominant source of IL-23 in inflamed tissue in psoriasis, ulcerative colitis, and Crohn’s disease. Guselkumab has demonstrated in vitro blocking of IL-23 and binding to CD64. These results indicate that guselkumab is able to neutralise IL-23 at the cellular source of inflammation.
Pharmacodynamic effects
In a Phase I study, treatment with guselkumab resulted in reduced expression of IL-23/Th17 pathway genes and psoriasis-associated gene expression profiles, as shown by analyses of mRNA obtained from lesional skin biopsies of patients with plaque psoriasis at Week 12 compared to baseline. In the same Phase I study, treatment with guselkumab resulted in improvement of histological measures of psoriasis at Week 12, including reductions in epidermal thickness and T-cell density. In addition, reduced serum IL-17A, IL-17F and IL-22 levels compared to placebo were observed in guselkumab treated patients in Phase II and Phase III plaque psoriasis studies. These results are consistent with the clinical benefit observed with guselkumab treatment in plaque psoriasis.
In psoriatic arthritis patients in Phase III studies, serum levels of acute phase proteins C-reactive protein, serum amyloid A, and IL-6, and Th17 effector cytokines IL-17A, IL-17F and IL-22 were elevated at baseline. Guselkumab decreased the levels of these proteins within 4 weeks of initiation of treatment. Guselkumab further reduced the levels of these proteins by Week 24 compared to baseline and also to placebo.

Paediatric population
Steady-state serum trough concentrations of guselkumab were achieved by Week 20 in paediatric patients 6 to 17 years of age with moderate to severe plaque psoriasis treated with guselkumab subcutaneous injection using the 45 mg/0.45 mL pre-filled pen or the 100 mg pre-filled syringe (see section 4.2), and were within the range of those observed in adults.
The recommended dosing regimen results in similar predicted serum guselkumab exposure in paediatric patients with plaque psoriasis as compared to adults across the body weight range.
Adult population
Absorption
Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab reached a mean (± SD) maximum serum concentration (Cmax) of 8.09 ± 3.68 mcg/mL by approximately 5.5 days post dose. The absolute bioavailability of guselkumab following a single 100 mg subcutaneous injection was estimated to be approximately 49% in healthy subjects.
In patients with plaque psoriasis, following subcutaneous administrations of guselkumab 100 mg at Weeks 0 and 4, and every 8 weeks thereafter, steady-state serum guselkumab concentrations were achieved by Week 20. The mean (± SD) steady-state trough serum guselkumab concentrations in two Phase III studies in patients with plaque psoriasis were 1.15 ± 0.73 mcg/mL and 1.23 ± 0.84 mcg/mL.
Distribution
Mean volume of distribution during the terminal phase (Vz) following a single intravenous administration to healthy subjects ranged from approximately 7 to 10 L across studies.
Biotransformation
The exact pathway through which guselkumab is metabolised has not been characterised. As a human IgG mAb, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.
Elimination

Absorption
Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab reached a mean (± SD) maximum serum concentration (Cmax) of 8.09 ± 3.68 mcg/mL by approximately 5.5 days post dose. The absolute bioavailability of guselkumab following a single 100 mg subcutaneous injection was estimated to be approximately 49% in healthy subjects.
In patients with plaque psoriasis, following subcutaneous administrations of guselkumab 100 mg at Weeks 0 and 4, and every 8 weeks thereafter, steady-state serum guselkumab concentrations were achieved by Week 20. The mean (± SD) steady-state trough serum guselkumab concentrations in two Phase III studies in patients with plaque psoriasis were 1.15 ± 0.73 mcg/mL and 1.23 ± 0.84 mcg/mL.
The pharmacokinetics of guselkumab in patients with psoriatic arthritis was similar to that in patients with psoriasis. Following subcutaneous administration of guselkumab 100 mg at Weeks 0, 4, and every 8 weeks thereafter, mean steady-state trough serum guselkumab concentration was also approximately 1.2 mcg/mL. Following subcutaneous administration of guselkumab 100 mg every 4 weeks, mean steady-state trough serum guselkumab concentration was approximately 3.8 mcg/mL.
The pharmacokinetics of guselkumab were similar in patients with ulcerative colitis and Crohn’s disease. Following the recommended intravenous induction dose regimen of guselkumab 200 mg at Weeks 0, 4, and 8, mean peak serum guselkumab concentration at Week 8 was 68.27 mcg/mL in patients with ulcerative colitis, and 70.5 mcg/mL in patients with Crohn’s disease.
Following the recommended subcutaneous induction dose regimen of guselkumab 400 mg at Weeks 0, 4, and 8, mean peak serum guselkumab concentration at Week 8 was estimated to be 28.8 mcg/mL in patients with ulcerative colitis, and 27.7 mcg/mL in patients with Crohn’s disease.

Absorption
Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab reached a mean (± SD) maximum serum concentration (Cmax) of 8.09 ± 3.68 mcg/mL by approximately 5.5 days post dose. The absolute bioavailability of guselkumab following a single 100 mg subcutaneous injection was estimated to be approximately 49% in healthy subjects.
In patients with plaque psoriasis, following subcutaneous administrations of guselkumab 100 mg at Weeks 0 and 4, and every 8 weeks thereafter, steady-state serum guselkumab concentrations were achieved by Week 20. The mean (± SD) steady-state trough serum guselkumab concentrations in two Phase III studies in patients with plaque psoriasis were 1.15 ± 0.73 mcg/mL and 1.23 ± 0.84 mcg/mL.
The pharmacokinetics of guselkumab in patients with psoriatic arthritis was similar to that in patients with psoriasis. Following subcutaneous administration of guselkumab 100 mg at Weeks 0, 4, and every 8 weeks thereafter, mean steady-state trough serum guselkumab concentration was also approximately 1.2 mcg/mL. Following subcutaneous administration of guselkumab 100 mg every 4 weeks, mean steady-state trough serum guselkumab concentration was approximately 3.8 mcg/mL.
The pharmacokinetics of guselkumab were similar in patients with ulcerative colitis and Crohn’s disease. Following the recommended intravenous induction dose regimen of guselkumab 200 mg at Weeks 0, 4, and 8, mean peak serum guselkumab concentration at Week 8 was 68.27 mcg/mL in patients with ulcerative colitis, and 70.5 mcg/mL in patients with Crohn’s disease.
Following the recommended subcutaneous induction dose regimen of guselkumab 400 mg at Weeks 0, 4, and 8, mean peak serum guselkumab concentration at Week 8 was estimated to be 28.8 mcg/mL in patients with ulcerative colitis and 27.7 mcg/mL in patients with Crohn’s disease.