Adverse reactions : תופעות לוואי

4.8         Undesirable effects

Summary of the safety profile

The most frequently reported adverse reactions are upper respiratory tract infections (17.7%) (most frequently nasopharyngitis, rhinitis).

Tabulated list of adverse reactions

Adverse reactions from clinical studies and post-marketing reports (Table 3) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions 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 reaction is based on 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); and not known (cannot be estimated from the available data).

Over 18,000 patients have been treated with secukinumab in blinded and open-label clinical studies in various indications (plaque psoriasis, psoriatic arthritis, axial spondyloarthritis and other autoimmune conditions), representing 30,565 patient years of exposure. Of these, over 11,700 patients were exposed to secukinumab for at least one year. The safety profile of secukinumab is consistent across all indications.



COS POW API May23 V9                                                   Based on EU reference 04/2023 Table 3          List of adverse reactions in clinical studies1) and post-marketing experience System Organ Class         Frequency          Adverse reaction
Infections and             Very common        Upper respiratory tract infections infestations               Common             Oral herpes
Tinea pedis
Uncommon           Oral candidiasis
Otitis externa
Lower respiratory tract infections
Not known          Mucosal and cutaneous candidiasis (including oesophageal candidiasis)
Blood and lymphatic        Uncommon           Neutropenia system disorders
Immune system              Rare               Anaphylactic reactions disorders
Nervous system             Common             Headache disorders
Eye disorders              Uncommon           Conjunctivitis
Respiratory, thoracic      Common             Rhinorrhoea and mediastinal disorders
Gastrointestinal           Common             Diarrhoea disorders                  Common             Nausea
Uncommon           Inflammatory bowel disease
Skin and subcutaneous Uncommon                Urticaria tissue disorders                              Dyshidrotic eczema
Rare               Exfoliative dermatitis2)
Hypersensitivity vasculitis
Not known          Pyoderma gangrenosum
General disorders and      Common             Fatigue administration site conditions
1)
Placebo-controlled clinical studies (phase III) in plaque psoriasis, PsA, AS and nr-axSpA patients exposed to 300 mg, 150 mg, 75 mg or placebo up to 12 weeks (psoriasis) or 16 weeks (PsA, AS and nr-axSpA) treatment duration
2)
Cases were reported in patients with psoriasis diagnosis

Description of selected adverse reactions

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. The majority of infections consisted of non-serious and mild to moderate upper respiratory tract infections, such as nasopharyngitis, which did not necessitate treatment discontinuation. There was an increase in mucosal or cutaneous candidiasis, consistent with the mechanism of action, but the cases were mild or moderate in severity, non-serious, responsive to standard treatment and did not necessitate treatment discontinuation. Serious infections occurred in 0.14% of patients treated with secukinumab and in 0.3% of patients treated with placebo (see section 4.4).
Over the entire treatment period (a total of 3,430 patients treated with secukinumab for up to 52 weeks 
COS POW API May23 V9                                                  Based on EU reference 04/2023 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 observed in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non- radiographic axial spondyloarthritis) clinical studies were similar to those observed in the psoriasis studies.

Neutropenia
In psoriasis phase III 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 secukinumab were reported in the remaining 3 cases.

The frequency of neutropenia in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) was 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 reaction to secukinumab were observed (see also section 4.4).

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 neutralising, but this was not associated with loss of efficacy or pharmacokinetic abnormalities.

Paediatric population

Undesirable effects in paediatric patients from the age of 6 years with plaque psoriasis The safety of secukinumab was assessed in two phase III studies in paediatric patients with plaque psoriasis. The first study (paediatric study 1) 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 study (paediatric study 2) 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 two studies was consistent with the safety profile reported in adult plaque psoriasis patients.

Undesirable effects in paediatric patients with JIA
The safety of secukinumab was also assessed in a phase III study in 86 juvenile idiopathic arthritis patients with ERA and JPsA from 2 to less than 18 years of age. The safety profile reported in this study was consistent with the safety profile reported in adult patients.

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. Any suspected adverse events COS POW API May23 V9                                                  Based on EU reference 04/2023 should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il