Summary of the safety profile: Over 18,000 patients have been treated with Cosentyx in blinded and open-label clinical studies in various indications (plaque psoriasis and other autoimmune conditions), representing 30,565 patient years of exposure.
Of these, over 11,500 patients were exposed to Cosentyx for at least one year.
Adverse reactions in plaque psoriasis: Four placebo-controlled phase III studies in plaque psoriasis were pooled to evaluate the safety of Cosentyx in comparison to placebo up to 12 weeks after treatment initiation. In total, 2,076 patients were evaluated (692 patients on 150 mg, 690 patients on 300 mg and 694 patients on placebo).
The most frequently reported adverse drug reactions (ADRs) were upper respiratory tract infections (most frequently nasopharyngitis, rhinitis). Most of the events were mild or moderate in severity.
In the placebo-controlled period of plaque psoriasis phase III studies the proportion of patients who discontinued treatment due to adverse events was approximately 1.2% in the Cosentyx arm and 1.2% in the placebo arm.
ADRs from psoriasis clinical studies (Table 12) are listed by MedDRA system organ class. Within each system organ class, the ADRs are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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). (See Table 12.)
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Adverse drug reactions from spontaneous reports and literature cases (frequency not known): The following adverse drug reactions have been derived from post-marketing experience with Cosentyx via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness. (See Table 13.)
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Infections: In the placebo-controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated with Cosentyx and 694 patients treated with placebo for up to 12 weeks), infections were reported in 28.7% of patients treated with Cosentyx compared with 18.9% of patients treated with placebo. Most of these were mild or moderate. Serious infections occurred in 0.14% of patients treated with Cosentyx and in 0.3% of patients treated with placebo (see PRECAUTIONS).
Over the entire treatment period (a total of 3,430 patients treated with Cosentyx for up to 52 weeks for the majority of patients), infections were reported in 47.5% of patients treated with Cosentyx (0.9 per patient year of follow-up). Serious infections were reported in 1.2% of patients treated with Cosentyx (0.015 per patient-year of follow-up).
Infection rates as observed in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) clinical studies were similar to what was observed in the psoriasis studies.
Neutropenia: In psoriasis phase 3 clinical studies, neutropenia was more frequently observed with secukinumab than with placebo, but most cases were mild, transient and reversible. Neutropenia <1.0-0.5x109/l (CTCAE Grade 3) was reported in 18 out of 3,430 (0.5%) patients on secukinumab, with no dose dependence and no temporal relationship to infections in 15 out of 18 cases. There were no reported cases of more severe neutropenia. Non-serious infections with usual response to standard care and not requiring discontinuation of Cosentyx were reported in the remaining 3 cases.
The frequency of neutropenia in psoriatic arthritis and ankylosing spondylitis is similar to psoriasis.
Rare cases of neutropenia <0.5x109/l (CTCAE Grade 4) were reported.
Hypersensitivity reactions: In clinical studies, urticaria and rare cases of anaphylactic reactions to Cosentyx were observed.
Immunogenicity: In psoriasis, psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) clinical studies, less than 1% of patients treated with Cosentyx developed antibodies to secukinumab up to 52 weeks of treatment. About half of the treatment emergent anti-drug antibodies were neutralizing, but this was not associated with loss of efficacy or PK abnormalities.
Adverse reactions in psoriatic arthritis: Cosentyx was studied in five placebo-controlled psoriatic arthritis trials with 2,754 patients (1,871 patients on Cosentyx and 883 patients on placebo) with a total exposure of 4,478 patient years of study exposure on Cosentyx. The safety profile observed in patients with psoriatic arthritis treated with Cosentyx is consistent with the safety profile in psoriasis.
Adverse reactions in axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis): Cosentyx was studied in three placebo-controlled ankylosing spondylitis trials with 816 patients (544 patients on Cosentyx and 272 patients on placebo). The median duration of exposure for secukinumab-treated patients was 469 days in AS 1 Study, 460 days in AS 2 Study, and 1,142 days in AS 3 Study. Cosentyx was also studied in one placebo-controlled non-radiographic axial spondyloarthritis trial with 555 patients (369 patients on Cosentyx and 186 patients on placebo) for a total of 588 patient-years of study exposure (median duration of exposure for secukinumab-treated patients: 395 days). The safety profile observed in patients with axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) treated with Cosentyx is consistent with the safety profile in psoriasis.