Fraizeron Adverse Reactions

Summary of the safety profile: Over 20,000 patients have been treated with secukinumab in blinded and open-label clinical studies in various indications (plaque psoriasis and other autoimmune conditions), representing 34,908 patient years of exposure.
Of these, over 14,000 patients were exposed to secukinumab for at least one year.
Adverse reactions in plaque psoriasis: Adult patients: Four placebo-controlled phase III studies in plaque psoriasis were pooled to evaluate the safety of secukinumab 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 secukinumab arm and 1.2% in the placebo arm.
ADRs from psoriasis clinical studies (Table 17) 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 17.)

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Pediatric patients: The safety of secukinumab was assessed in two phase III studies in pediatric patients with plaque psoriasis. The first was a double-blind, placebo-controlled study of 162 patients from 6 to less than 18 years of age with severe plaque psoriasis. The second is an open-label study of 84 patients from 6 to less than 18 years of age with moderate to severe plaque psoriasis. The safety profile reported in these studies was consistent with the safety profile reported in adult plaque psoriasis patients.
The safety of Fraizeron was also assessed in a Phase III study in 86 pediatric patients from 2 to less than 18 years of age with the ERA and JPsA categories of JIA. The safety profile reported in this study was consistent with the safety profile reported in adult patients.
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 secukinumab 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 18.)

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Description of selected adverse drug reactions: Adult patients: Infections: In the placebo-controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated with secukinumab and 694 patients treated with placebo for up to 12 weeks), infections were reported in 28.7% of patients treated with secukinumab 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 secukinumab and in 0.3% of patients treated with placebo (see Precautions).
Over the entire treatment period (a total of 3,430 patients treated with secukinumab for up to 52 weeks for the majority of patients), infections were reported in 47.5% of patients treated with secukinumab (0.9 per patient-year of follow-up). Serious infections were reported in 1.2% of patients treated with secukinumab (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 <1.0-0.5 x 10⁹/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 secukinumab 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 <0.5 x 10⁹/l (CTCAE Grade 4) were reported.
Hypersensitivity reactions: In clinical studies, urticaria and rare cases of anaphylactic reactions to secukinumab 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 secukinumab 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: Secukinumab was studied in five placebo-controlled psoriatic arthritis trials with 2,754 patients (1,871 patients on secukinumab and 883 patients on placebo) with a total exposure of 4,478 patient years of study exposure on secukinumab. The safety profile observed in patients with psoriatic arthritis treated with secukinumab is consistent with the safety profile in psoriasis.
Adverse reactions in axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis): Secukinumab was studied in three placebo-controlled ankylosing spondylitis trials with 816 patients (544 patients on secukinumab 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. Secukinumab was also studied in one placebo-controlled non-radiographic axial spondyloarthritis trial with 555 patients (369 patients on secukinumab 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 secukinumab is consistent with the safety profile in psoriasis.