Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important, active infection, e.g. active tuberculosis (see section 4.4).
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Secukinumab has the potential to increase the risk of infections. Serious infections have been observed in patients receiving secukinumab in the post-marketing setting. Caution should be exercised when considering the use of secukinumab in patients with a chronic infection or a history of recurrent infection.
Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and secukinumab should not be administered until the infection resolves.
In clinical studies, infections have been observed in patients receiving secukinumab (see section 4.8). Most of these were mild or moderate upper respiratory tract infections such as nasopharyngitis and did not require treatment discontinuation.
Related to the mechanism of action of secukinumab, non-serious mucocutaneous candida infections were more frequently reported for secukinumab than placebo in the psoriasis clinical studies (3.55 per 100 patient years for secukinumab 300 mg versus 1.00 per 100 patient years for placebo) (see section 4.8).
No increased susceptibility to tuberculosis was reported from clinical studies. However, secukinumab should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered prior to initiation of secukinumab in patients with latent tuberculosis.
Cases of new or exacerbations of inflammatory bowel disease have been reported with secukinumab (see section 4.8). Secukinumab is not recommended in patients with inflammatory bowel disease. If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, secukinumab should be discontinued and appropriate medical management should be initiated.
In clinical studies, rare cases of anaphylactic reactions have been observed in patients receiving secukinumab. If an anaphylactic or other serious allergic reactions occur, administration of secukinumab should be discontinued immediately and appropriate therapy initiated.
The removable needle cap of Cosentyx 150 mg solution for injection in pre-filled syringe and Cosentyx 150 mg solution for injection in pre-filled pen contains a derivative of natural rubber latex. No natural rubber latex has to date been detected in the removable needle cap. Nevertheless, the use of Cosentyx 150 mg solution for injection in pre-filled syringe and Cosentyx 150 mg solution for injection in pre-filled pen in latex-sensitive individuals has not been studied and there is therefore a potential risk of hypersensitivity reactions which cannot be completely ruled out.
Live vaccines should not be given concurrently with secukinumab.
Patients receiving secukinumab may receive concurrent inactivated or non-live vaccinations. In a study, after meningococcal and inactivated influenza vaccinations, a similar proportion of healthy volunteers treated with 150 mg of secukinumab and those treated with placebo were able to mount an adequate immune response of at least a 4-fold increase in antibody titres to meningococcal and influenza vaccines. The data suggest that secukinumab does not suppress the humoral immune response to the meningococcal or influenza vaccines.
Prior to initiating therapy with Cosentyx, it is recommended that paediatric patients receive all age-appropriate immunisations as per current immunisation guidelines.
In psoriasis studies, the safety and efficacy of secukinumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated. Secukinumab was administered concomitantly with methotrexate (MTX), sulfasalazine and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and ankylosing spondylitis). Caution should be exercised when considering concomitant use of other immunosuppressants and secukinumab (see also section 4.5).
Live vaccines should not be given concurrently with secukinumab (see also section 4.4).
In a study in adult subjects with plaque psoriasis, no interaction was observed between secukinumab and midazolam (CYP3A4 substrate).
No interaction was seen when secukinumab was administered concomitantly with methotrexate (MTX) and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and axial spondyloarthritis).
Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment.
There are no adequate data from the use of secukinumab in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Cosentyx during pregnancy.
It is not known whether secukinumab is excreted in human milk. Immunoglobulins are excreted in human milk and it is not known if secukinumab is absorbed systemically after ingestion. Because of the potential for adverse reactions in nursing infants from secukinumab, a decision on whether to discontinue breast-feeding during treatment and up to 20 weeks after treatment or to discontinue therapy with Cosentyx must be made taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.
The effect of secukinumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.
Cosentyx has no or negligible influence on the ability to drive and use machines.
The most frequently reported adverse reactions are upper respiratory tract infections (17.1%) (most frequently nasopharyngitis, rhinitis).
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 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 20 000 patients have been treated with secukinumab in blinded and open-label clinical studies in various indications (plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, hidradenitis suppurativa 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. The safety profile of secukinumab is consistent across all indications.
Table 3. List of adverse reactions in clinical studies1 and post-marketing experience:
| System organ class | Frequency | Adverse reaction |
|---|---|---|
| Infections and infestations | Very common | Upper respiratory tract infections |
| Common | Oral herpes | |
| Uncommon | Oral candidiasis Otitis externa Lower respiratory tract infections Tinea pedis | |
| Not known | Mucosal and cutaneous candidiasis (including oesophageal candidiasis) | |
| Blood and lymphatic system disorders | Uncommon | Neutropenia |
| Immune system disorders | Rare | Anaphylactic reactions |
| Nervous system disorders | Common | Headache |
| Eye disorders | Uncommon | Conjunctivitis |
| Respiratory, thoracic and mediastinal disorders | Common | Rhinorrhoea |
| Gastrointestinal disorders | Common | Diarrhoea Nausea |
| Uncommon | Inflammatory bowel disease | |
| Skin and subcutaneous tissue disorders | Uncommon | Urticaria Dyshidrotic eczema |
| Rare | Exfoliative dermatitis2 Hypersensitivity vasculitis | |
| Not known | Pyoderma gangrenosum | |
| General disorders and administration site conditions | Common | Fatigue |
1 Placebo-controlled clinical studies (phase III) in plaque psoriasis, PsA, AS, nr-axSpA and HS patients exposed to 300 mg, 150 mg, 75 mg or placebo up to 12 weeks (psoriasis) or 16 weeks (PsA, AS, nr-axSpA and HS) treatment duration
2 Cases were reported in patients with psoriasis diagnosis
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 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.
Patients with hidradenitis suppurativa are more susceptible to infections. In the placebo-controlled period of clinical studies in hidradenitis suppurativa (a total of 721 patients treated with secukinumab and 363 patients treated with placebo for up to 16 weeks), infections were numerically higher compared to those observed in the psoriasis studies (30.7% of patients treated with secukinumab compared with 31.7% in patients treated with placebo). Most of these were non-serious, mild or moderate in severity and did not require treatment discontinuation or interruption.
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, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) and hidradenitis suppurativa was similar to psoriasis.
Rare cases of neutropenia <0.5x109/l (CTCAE grade 4) were reported.
In clinical studies, urticaria and rare cases of anaphylactic reaction to secukinumab were observed (see also section 4.4).
In psoriasis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) and hidradenitis suppurativa 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.
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.
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 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.
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