Cosentyx is indicated for the treatment of: moderate to severe plaque psoriasis (PsO) in adults, adolescents and children from the age of 6 years who are candidates for systemic therapy; active psoriatic arthritis in adult patients, alone or in combination with MTX, when the response to previous DMARD therapy has been inadequate; active ankylosing spondylitis in adults who have responded inadequately to conventional therapy; active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated CRP and/or MRI evidence in adults who have responded inadequately to NSAIDs.
Cosentyx offers the reassurance of a safety profile that is…
The most frequent adverse events reported included nasopharyngitis, hypertension, back pain, upper respiratory tract infection and headache2
Summary of adverse reactions in clinical studies* and post-marketing experience5
| System Organ Class | Adverse reaction |
|---|---|
| Infections and infestations | Upper respiratory tract infections |
| System Organ Class | Adverse reaction |
|---|---|
| Infections and infestations | Oral herpes |
| Tinea pedis | |
| Nervous system disorders | Headache |
| Respiratory, thoracic and mediastinal disorders | Rhinorrhoea |
| Gastrointestinal disorders | Diarrhoea |
| Nausea | |
| General disorders and administration site conditions | Fatigue |
| System Organ Class | Adverse reaction |
|---|---|
| Infections and infestations | Oral candidiasis |
| Otitis externa | |
| Lower respiratory tract infections | |
| Blood and lymphatic system disorders | Neutropenia |
| Eye disorders | Conjunctivitis |
| Gastrointestinal disorders | Inflammatory bowel disease |
| Skin and subcutaneous tissue disorders | Urticaria |
| System Organ Class | Adverse reaction |
|---|---|
| Immune system disorders | Anaphylactic reactions |
| Skin and subcutaneous tissue disorders | Exfoliative dermatitis§ |
| Hypersensitivity vasculitis |
| System Organ Class | Adverse reaction |
|---|---|
| Infections and infestations | Mucosal and cutaneous candidiasis (including oesophageal candidiasis) |
Safety data and selected AEs from 21 clinical trials9
| PsO studies Any Cosentyx (N=5181) |
PsA studies Any Cosentyx (N=1380) |
AS studies Any Cosentyx (N=794) |
|
|---|---|---|---|
| Total exposure, patient-years | 10,416.9 | 3866.9 | 1943.1 |
| Min–max exposure (days) | 1−1825 | 8−1827 | 1−1530 |
| Death, n (%) | 9 (0.2) | 11 (0.8) | 5 (0.6) |
| Discontinuations due to AEs, n (%) | 331 (6.4) | 104 (7.5) | 58 (7.3) |
| EAIR per 100 patient-years (95% CI) | |||
| Any AE | 204.4 (198.4, 210.5) | 147.0 (138.9, 155.5) | 140.1 (129.8, 151.0) |
| Any serious AE | 6.9 (6.3, 7.4) | 7.9 (7.0, 8.9) | 6.3 (5.2, 7.6) |
| Most common AEs* | |||
| Viral URTI† | 21.0 (19.9, 22.0) | 12.1 (10.9, 13.4) | 9.8 (8.4, 11.5) |
| Headache | 6.2 (5.8, 6.8) | 3.8 (3.2, 4.5) | 5.3 (4.3, 6.5) |
| Diarrhoea | 3.8 (3.4, 4.2) | 3.7 (3.1, 4.4) | 5.2 (4.2, 6.4) |
| URTI | 5.4 (4.9, 5.9) | 9.1 (8.1, 10.2) | 5.2 (4.2, 6.4) |
| Selected AEs | |||
| Serious infections‡ | 1.4 (1.2, 1.6) | 1.9 (1.5, 2.4) | 1.2 (0.8, 1.8) |
| Candida infections§ | 2.2 (1.9, 2.5) | 1.5 (1.1, 2.0) | 0.7 (0.4, 1.2) |
| IBD¶ | 0.01 (0.00, 0.05) | 0.05 (0.01, 0.2) | 0.1 (0.0, 0.3) |
| Crohn’s disease¶ | 0.05 (0.02, 0.1) | 0.08 (0.02, 0.2) | 0.4 (0.2, 0.8) |
| Ulcerative colitis¶ | 0.1 (0.07, 0.2) | 0.08 (0.02, 0.2) | 0.2 (0.1, 0.5) |
| MACE|| | 0.3 (0.2, 0.5) | 0.4 (0.3, 0.7) | 0.6 (0.3, 1.1) |
| Neutropenia¶ | 0.3 (0.2, 0.4) | 0.2 (0.1, 0.4) | 0.5 (0.3, 1.0) |
| Uveitis¶ | 0.02 (0.0, 0.07) | 0.1 (0.0, 0.2) | 1.4 (0.9, 2.0) |
| Malignancy** | 0.8 (0.6, 1.0) | 1.1 (0.8, 1.5) | 0.5 (0.2, 0.9) |
Table adapted from Deodhar et al. 2019.9
Adverse events were reported as exposure adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received one or more doses of Cosentyx. Approximation was not done if EAIR is less than 0.1.
Some of the doses and dose regimes used in these studies are not approved for use (including 10 mg/kg intravenous loading and 75 mg subcutaneous dose). Individual patient dosing may vary - please consult the Prescribing Information for full details or refer to the Cosentyx SmPC for full prescribing information.
*AEs in the Cosentyx group that occurred with an incidence rate >5.0 per 100 patient-years during the entire safety period in any of the pooled groups.
†Includes cases of common cold (low-level term).
‡Values are based on system organ class: infections and infestations.
§Values are based on the high-level term.
¶Values are based on the preferred term.
||Values are based on Novartis Medical Dictionary for Regulatory Activities query, which comprises (1) any myocardial infarction, (2) any cardiovascular accident, and (3) all other cardiovascular events that are fatal, out of a listing of 2200+ terms.
**Values are based on standardised MedDRA query.
From an extension to the SCULPTURE study2
| Cosentyx 300 mg | |||||
|---|---|---|---|---|---|
| Year 1 N=168 |
Year 2 N=168 |
Year 3 N=157 |
Year 4 N=142 |
Year 5 N=134 |
|
| n (incidence rate per 100 subject-years) | |||||
| Duration of exposure (patient-years)* | 168.0 | 162.8 | 148.8 | 136.5 | 142.0 |
| All AEs | 131 (204.6) | 126 (166.3) | 109 (139.2) | 91 (118.5) | 77 (87.2) |
| All non-fatal SAEs | 14 (8.8) | 11 (6.9) | 13 (9.1) | 13 (10.1) | 11 (8.0) |
| Death | 0 | 0 | 0 | 0 | 1 (0.7)† |
| Most frequent AEs | |||||
| Nasopharyngitis | 30 (20.1) | 27 (18.1) | 25 (18.8) | 17 (13.5) | 15 (11.1) |
| Hypertension | 11 (6.8) | 8 (5.1) | 3 (2.0) | 7 (5.3) | 5 (3.6) |
| Back pain | 7 (4.3) | 9 (5.7) | 9 (6.2) | 3 (2.2) | 3 (2.1) |
| URTI | 12 (7.5) | 11 (7.1) | 5 (3.5) | 5 (3.8) | 5 (3.6) |
| Headache | 10 (6.2) | 7 (4.4) | 4 (2.7) | 3 (2.2) | 1 (0.7) |
| Selected rare AEs | |||||
| Opportunistic infections (other than TB and candidiasis) | 0 | 0 | 0 | 0 | 0 |
| TB | 0 | 0 | 0 | 0 | 0 |
| Candida infections | |||||
| Vulvovaginal candidiasis | 3 (1.8) | 3 (1.9) | 1 (0.7) | 0 | 0 |
| Oral candidiasis | 0 | 1 (0.6) | 0 | 1 (0.7) | 1 (0.7) |
| Neutropenia | 0 | 0 | 0 | 0 | 0 |
| MACE | 0 | 0 | 0 | 1 (0.7) | 1 (0.7)† |
| Crohn’s disease | 0 | 0 | 0 | 0 | 0 |
| Ulcerative colitis | 0 | 2 (1.2)‡ | 1 (0.7) | 0 | 0 |
| Malignant or unspecified tumours (excluding NMSC) | 0 | 2 (1.2)§ | 0 | 0 | 1 (0.7)¶ |
Table adapted from Bissonnette et al. 2018.2
Only subjects who completed the SCULPTURE core study and continued into the extension are included in this analysis. A subject with multiple occurrences of the same AE in a one-year interval was counted only once, while a subject with multiple occurrences of the same AE in different year intervals was counted for each year.
*Patient exposure is calculated as a sum of individual subject durations in days divided by 365 for each interval.
†Death was due to MACE, which was not considered by the investigators to be related to study drug; patient had ≥2 pre-existing MACE risk factors.
‡Of the two cases of ulcerative colitis in year 2, one case was an exacerbation of previously existing ulcerative colitis; the exposure-adjusted incidence rate for new-onset ulcerative colitis cases for the entire study duration (5 years) was 0.27.
§One case of cholangiocarcinoma, one case of invasive ductal breast carcinoma.
¶One case of breast cancer.
FIXTURE double-blind RCT6
| Variable | Induction period* | Entire study*† | ||||
|---|---|---|---|---|---|---|
| Cosentyx 300 mg (N=326) | Etanercept (N=323) | Placebo (N=327) | Cosentyx 300 mg (N=467) | Etanercept (N=323) | Placebo (N=327) | |
| Exposure to study treatment – days | 82.8±9.8 | 82.6±9.4 | 81.7±11.4 | 320.7±75.3 | 331.9±89.7 | 95.3±61.0 |
| no. of patients with event (percent) | no. of patients with event (no. of cases per 100 patient-yr) | |||||
| Any adverse event | 181 (55.5) | 186 (57.6) | 163 (49.8) | 376 (252.0) | 253 (243.4) | 168 (329.7) |
| Death | 0 | 0 | 0 | 0 | 0 | 0 |
| Nonfatal serious adverse event | 4 (1.2) | 3 (0.9) | 6 (1.8) | 27 (6.8) | 20 (7.0) | 7 (8.3) |
| Discontinuation due to adverse event‡ | 4 (1.2) | 6 (1.9) | 3 (0.9) | 14 | 12 | 3 |
| Infection or infestation | 87 (26.7) | 79 (24.5) | 63 (19.3) | 269 (105.4) | 170 (91.4) | 65 (89.5) |
| Common adverse event§ | ||||||
| Nasopharyngitis | 35 (10.7) | 36 (11.1) | 26 (8.0) | 122 (35.2) | 86 (35.7) | 26 (32.8) |
| Headache | 30 (9.2) | 23 (7.1) | 23 (7.0) | 58 (15.7) | 40 (15.2) | 24 (29.6) |
| Diarhoea | 17 (5.2) | 11 (3.4) | 6 (1.8) | 38 (9.9) | 22 (7.9) | 7 (8.4) |
| Pruritus | 8 (2.5) | 8 (2.5) | 11 (3.4) | 16 (4.0) | 16 (5.7) | 11 (13.2) |
| Arthralgia | 5 (1.5) | 12 (3.7) | 10 (3.1) | 24 (6.0) | 23 (8.2) | 10 (12.1) |
| Upper respiratory tract infection | 7 (2.1) | 7 (2.2) | 3 (0.9) | 26 (6.6) | 18 (6.4) | 3 (3.5) |
| Back pain | 8 (2.5) | 9 (2.8) | 6 (1.8) | 31 (7.9) | 26 (9.3) | 6 (7.1) |
| Cough | 11 (3.4) | 4 (1.2) | 4 (1.2) | 30 (7.6) | 12 (4.2) | 4 (4.8) |
| Hypertension | 5 (1.5) | 5 (1.5) | 4 (1.2) | 20 (5.0) | 14 (4.9) | 4 (4.7) |
| Nausea | 8 (2.5) | 4 (1.2) | 7 (1.2) | 11 (2.7) | 7 (2.4) | 7 (8.3) |
| Oropharyngeal pain | 9 (2.8) | 4 (1.2) | 7 (1.2) | 25 (6.3) | 10 (3.5) | 7 (8.3) |
Table adapted from Langley et al. 20176
*Plus–minus values are means ±SD. The induction period was defined as the period from baseline through Week 12, and the entire study period as the period from baseline through Week 52.
†Patients in the placebo group who did not meet the criteria for PASI 75 at Week 12 underwent randomisation again to Cosentyx at a dose of 300 mg or 150 mg (data not shown as this dose is not approved for use in PsO). In the analysis for the entire study period, the placebo group includes all the patients who received placebo during the induction period, which includes the 16 patients who met the criteria for PASI 75 at Week 12, who continued to receive placebo during the maintenance period (Week 13 through Week 52).
‡Exposure-adjusted incidence rates were not calculated for discontinuations due to adverse events.
§The most common adverse events are expressed according to the preferred term in the Medical Dictionary for Regulatory Activities, version 16.0, and were events that occurred in at least 2.0% of the patients in the combined Cosentyx groups during the induction period or events that had an incidence rate of at least 5.0 cases per 100 patient-years in the combined Cosentyx groups during the entire treatment period. Adverse events are listed in decreasing order of frequency in the combined Cosentyx groups during the induction period. Please see Langley et al. 2017 for full data table. Data for Cosentyx 150 mg are not shown as this is not a licensed dose for PsO.
Some of the doses and dose regimes used in this study are not approved for use. Individual patient dosing may vary - please consult the Prescribing Information for full details or refer to the Cosentyx SmPC for full prescribing information.
CLEAR double-blind RCT10
| Variable | Cosentyx 300 mg (N=335) n (incidence rate per 100 subject-years) [95% CI] |
Ustekinumab (N=336) n (incidence rate per 100 subject-years) [95% CI] |
|---|---|---|
| Any AE | 286 (280.9) [249.3–315.4] | 278 (250.1) [221.6–281.3] |
| Serious AEs | 30 (9.6) [6.5–13.7] | 26 (8.5) [5.5–12.4] |
| Death | 0 | 1 |
| Discontinued treatment due to AE | 10 | 9 |
| System organ class | ||
| Infections and infestations* | 197 (98.4) [85.1–113.1] | 194 (95.8) [82.8–110.3] |
| Most frequent individual AEs† | ||
| Nasopharyngitis | 77 (27.1) [21.4–33.8] | 83 (31.0) [24.7–38.5] |
| Headache | 40 (13.5) [9.7–18.4] | 41 (14.2) [10.2–19.3] |
| Upper respiratory tract infection | 31 (10.1) [6.9–14.3] | 30 (9.9) [6.7–14.2] |
| Arthralgia | 25 (8.1) [5.3–12.0] | 28 (9.2) [6.1–13.3] |
| Diarrhoea | 23 (7.5) [4.7–11.2] | 24 (7.9) [5.1–11.8] |
| Back pain | 22 (7.1) [4.4–10.7] | 26 (8.5) [5.6–12.5] |
Table adapted from Blauvelt et al. 2017.10
Individual patient dosing may vary - please consult the Prescribing Information for full details or refer to the Cosentyx SmPC for full prescribing information.
*Primary system organ class AE.
†Preferred term AEs occurring at an incidence rate per 100 subject-years ≥5.0 in the treatment groups; sorted by descending order of incidence in the secukinumab treatment group.
*Placebo-controlled, Phase III clinical studies in PsO, PsA, AS and nr-axSpA. Some of the doses and dose regimes used in these studies are not approved for use.
AE, adverse event; AS, ankylosing spondylitis; CI, confidence interval; CRP, C-reactive protein; DMARD, disease-modifying anti-rheumatic drug; EAIR, exposure-adjusted incidence rate; IBD, inflammatory bowel disease; MACE, major adverse cardiovascular event; MedDRA, Medical Dictionary for Regulatory Activities; MRI, magnetic resonance imaging; MTX, methotrexate; N, number of patients in the analysis; n, number of patients with a response; NMSC, non-melanoma skin cancer; NSAID, non-steroidal anti-inflammatory drug; nr-axSpA, non-radiographic axial spondyloarthritis; PsA, psoriatic arthritis; RCT, randomised controlled trial; SAE, serious adverse event; SmPC, Summary of Product Characteristics; TB, tuberculosis; TNF, tumour necrosis factor; URTI, upper respiratory tract infection.
References
- Novartis rheumatology DOF UK 313.
- Bissonnette R et al. J Eur Acad Dermatol Venereol. 2018;32(9):1507–1514.
- Mease P et al. ACR Open Rheum 2020;2(1):18–25.
- Baraliakos X et al. RMD Open 2019;5(2):e001005.
- Cosentyx Summary of Product Characteristics.
- Langley RG et al. N Engl J Med. 2014;371(4):326–338.
- McInnes IB et al. Rheumatology. 2017;56:1993–2003.
- Baeten D et al. N Engl J Med. 2015;373(26):2534–2548.
- Deodhar A et al. Arthritis Res Ther 2019;21:111.
- Blauvelt A et al. J Am Acad Dermatol. 2017;76(1):60–69.