Tremfya Adverse Reactions

Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably causally associated with the use of guselkumab based on the comprehensive assessment of the available adverse event information. A causal relationship with guselkumab cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical studies experience in adult patients with psoriasis and psoriatic arthritis: The safety profile of TREMFYA in subjects with moderate to severe plaque psoriasis is based on data from the Phase 2 (PSO2001) and Phase 3 (VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, DISCOVER 1, DISCOVER 2) studies in 3940 subjects, including 2711 with plaque psoriasis and 1229 subjects with psoriatic arthritis. The duration of exposure to TREMFYA is presented in Table 17. (See Table 17.)

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Adverse reactions to TREMFYA are presented in Table 18. The frequency of adverse reactions was based on those that occurred during the placebo-controlled periods of the studies in psoriasis (VOYAGE 1 and VOYAGE 2) and psoriatic arthritis (DISCOVER 1 and DISCOVER 2). Overall, the safety profile was generally similar across doses and indications. Within each frequency grouping, the adverse reactions are presented within the designated system organ classes in order of decreasing frequency, using the following convention: Very common (≥1/10), Common (frequent) (≥1/100, <1/10), Uncommon (infrequent) (≥1/1000, <1/100), Rare (≥1/10000, <1/1000). (See Table 18.)

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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 previously mentioned) 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 19). 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. (See Table 19.)

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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 psoriasis 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.
Clinical studies experience in adult patients with palmoplantar pustulosis: The safety of TREMFYA was studied in one Phase 3 study of 157 Japanese subjects with palmoplantar pustulosis (PPP) treated with TREMFYA for up to 52 weeks. In general, the safety profile in this study was similar to that seen in previous studies in adults with plaque psoriasis and/or psoriatic arthritis (see Clinical studies experience in adult patients with psoriasis and psoriatic arthritis as previously mentioned).
Postmarketing data: In addition to the adverse reactions reported during clinical studies and listed previously, the following adverse reactions have been reported during postmarketing experience (Table 20). Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In the table, the frequencies are provided according to the following convention: Very common ≥1/10; Common ≥1/100 and <1/10; Uncommon ≥1/1000 and <1/100; Rare ≥1/10000 and <1/1000; Very rare <1/10000, including isolated reports; Not known Cannot be estimated from the available data. (See Table 20.)

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