Prescribing information

 

   

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…

Well established

Consistent

 

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     

  1. Novartis rheumatology DOF UK 313.
  2. Bissonnette R et al. J Eur Acad Dermatol Venereol. 2018;32(9):1507–1514.
  3. Mease P et al. ACR Open Rheum 2020;2(1):18–25.
  4. Baraliakos X et al. RMD Open 2019;5(2):e001005.
  5. Cosentyx Summary of Product Characteristics.
  6. Langley RG et al. N Engl J Med. 2014;371(4):326–338.
  7. McInnes IB et al. Rheumatology. 2017;56:1993–2003.
  8. Baeten D et al. N Engl J Med. 2015;373(26):2534–2548.
  9. Deodhar A et al. Arthritis Res Ther 2019;21:111.
  10. Blauvelt A et al. J Am Acad Dermatol. 2017;76(1):60–69.
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UK | March 2022 | 199713
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]