TREMFYA Solution for injection Ref.[8930] Active ingredients: Guselkumab

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.

Interactions with CYP450 substrates

In a Phase 1 study in subjects with moderate to severe plaque psoriasis, changes in systemic exposures (C_max and AUC_inf) 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.

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 no 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.

Summary of the safety profile

The most common adverse reaction was respiratory tract infections in approximately 14% of patients in the psoriasis and psoriatic arthritis clinical studies.

Tabulated list of adverse reactions

Table 1 provides a list of adverse reactions from psoriasis and psoriatic arthritis clinical studies as well as 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).

Table 1. List of adverse reactions:

Description of selected adverse reactions

Transaminases increased

In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, adverse events 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 q4w group and 8.3% in the q8w group) than in the placebo group (4.6%). Through 1 year, adverse events 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:

^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.

Neutrophil count decreased

In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, the adverse event 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 event 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 subjects 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%) subjects in the guselkumab q8w group, 4 (1.1%) subjects in the guselkumab q4w group, and 1 (0.3%) subject in the placebo group. One subject 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 subjects 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.

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 neutralizing, 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 neutralizing, 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.

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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.