Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Sekukinumab

Klassificering: C

Preparat: Cosentyx, Cosentyx®

ATC kod: L04AC10

Substanser: sekukinumab

Sammanfattning

I en randomiserad placebokontrollerad prövning vid icke-radiografisk spondylartrtit hade män en bättre behandlingsrespons vid 16-veckor. De flesta observationella studier vid axial spondylartrit och psoriasisartrit har funnit sämre behandlingsrespons och högre risk för behandlingsavbrott med sekukinumab hos kvinnor. Det finns även viss evidens för en högre risk för behandlingsavbrott för kvinnor vid psoriasis. Justerat för kroppsvikt är clearance för sekukinumab inte beroende av patientens kön.

Additional information

The prevalence of ankylosing spondylitis in the Swedish adult population is 0.2%, with more men than women affected (0.23% vs. 0.14%) [1]. The overall prevalence of psoriasis in the adult Swedish population is 1.2%, psoriatic arthritis affects about 20% of these patients. In both psoriasis and psoriatic arthritis men and women are affected equally [2].

Pharmacokinetics and dosing

Secukinumab exposure is significantly impacted by body weight. Response rates were numerically higher in low body weight than in high body weight individuals in the randomized clinical trials that were conducted before the market approval. The recommended dose is 300 mg once monthly, but the label includes information on higher and lower dosing. Patient’s sex does not significantly affect the clearance of secukinumab when adjusted for body weight [3, 4].  

Effects

Axial spondyloarthritis and psoriatic arthritisIn a post-hoc analysis of a randomized placebo-controlled trial of secukinumab in non-radiographic spondyloarthritis, response rates at 16 weeks were consistently higher in male than in female patients (255 men, 300 women) [5].In an observational study of determinants of secukinumab retention rates in spondyloarthropathies were examined (90 men, 48 women). In axial spondyloarthritis one year retention rates were higher in women than in men (95% vs. 77%). However, in psoriatic arthritis (PsA), one year retention rates were higher in men than in women (89% vs. 66%) [6]. Drug retention rates of secukinumab in PsA (27 men, 22 women) and axial spondyloarthritis (58 men, 37 women) were examined in another observational study. The 1-year retention was 66% and the 2-year retention rate was 43%. Adjusted for comorbidities and previous treatments, the hazard ratio (HR) for discontinuation for men was significantly lower (HR=0.54). The main causes for discontinuation were lack of efficacy (59%) and adverse events (36%). No difference was found between axial spondyloarthritis and PsA [7].Drug retention and treatment response in the treatment of PsA with secukinumab was examined in an observational study (251 men, 357 women). Overall, the 24-month retention rate was 71%. Men had lower rates of discontinuation (HR=0.68), and a higher chance of achieving minimal disease activity (HR=1.60) [8]. An observational study on drug retention in PsA included 4649 PsA patients treated with biologics (adalimumab, ustekinumab, secukinumab), of which 354 men and 533 women were treated with secukinumab. The risk of treatment discontinuation in adjusted Cox models was higher in women (HR=1.40) [9].

PsoriasisIn an observational study of secukinumab-treated psoriasis (224 men, 106 women, 21.5% with PsA), the overall 1-year drug retention rate was 83%. Patient’s sex was not significantly associated with treatment discontinuation in a univariate analysis [10]. A similar study on drug retention in secukinumab-treated psoriasis (241 men, 143 women) showed no difference in drug retention in adjusted models between men and women [11].An observational study in patients with psoriasis (572 men, 377 women) treated with anti-IL 17 agents (51% secukinumab) did not find a significant difference in drug retention between men and women [12]. A larger study (2037 men, 1275 women) on drug retention of IL‑12/23, IL‑17 and IL‑23 inhibitors in psoriasis patients (28% treated with secukinumab) found a lower risk of treatment discontinuation for men  (HR=0.84), but sex-divided data were not presented for secukinumab [13]. Another observational study on retention of biologics in psoriasis patients with or without PsA  (3843 men, 1791 women) found a higher risk of drug discontinuation in women (HR=1.13) [14]. The study included 738 patients treated with secukinumab but sex-divided data were not presented.  

Adverse effects

In an observational study (188 men, 127 women) on predictors for treatment discontinuation in biologics-treated psoriasis, women reported lower treatment satisfaction in terms of “side effects” and “global satisfaction”. Women also reported more relevant adverse events in the context of biologic therapy (i.e. fungal and herpes simplex infections). The study included 396 treatment episodes (24 for secukinumab) but secukinumab specific data were not reported [15].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler kvinnor än män hämtade ut läkemedel innehållande sekukinumab (ATC-kod L04AC10) på recept i Sverige år 2021, totalt 1 368 kvinnor och 1 154 män. Det motsvarar 2,7 respektive 2,2 personer per tiotusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 55-64 år hos kvinnor och i åldersgruppen 55-59 år hos män. I genomsnitt var läkemedel innehållande sekukinumab 1,6 gånger vanligare hos kvinnor [16].

Uppdaterat: 2022-12-22

Litteratursökningsdatum: 2022-10-17

Referenser

  1. Exarchou S, Lindström U, Askling J, Eriksson JK, Forsblad-d'Elia H, Neovius M et al. The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations: a nationwide register study. Arthritis Res Ther. 2015;17(1):118. PubMed
  2. Löfvendahl S, Theander E, Svensson Å, Carlsson KS, Englund M, Petersson IF. Validity of diagnostic codes and prevalence of physician-diagnosed psoriasis and psoriatic arthritis in southern Sweden--a population-based register study. PLoS One. 2014;9(5):e98024. PubMed
  3. Lee JE, Wang J, Florian J, Wang YM, Kettl D, Marcus K et al. Effect of Body Weight on Risk-Benefit and Dosing Regimen Recommendation of Secukinumab for the Treatment of Moderate to Severe Plaque Psoriasis. Clin Pharmacol Ther. 2019;106(1):78-80. PubMed
  4. Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - COSENTYX (secukinumab). Drugs@FDA [www]. [updated 2015-02-19, cited 2022-10-17]. länk
  5. Braun J, Blanco R, Marzo-Ortega H, Gensler LS, van den Bosch F, Hall S et al. Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT. Arthritis Res Ther. 2021;23(1):231. PubMed
  6. García-Dorta A, León-Suarez P, Peña S, Hernández-Díaz M, Rodríguez-Lozano C, González-Dávila E et al. Association of Gender, Diagnosis, and Obesity With Retention Rate of Secukinumab in Spondyloarthropathies: Results Form a Multicenter Real-World Study. Front Med (Lausanne). 2021;8:815881. PubMed
  7. Alonso S, Villa I, Fernández S, Martín JL, Charca L, Pino M et al. Multicenter Study of Secukinumab Survival and Safety in Spondyloarthritis and Psoriatic Arthritis: SEcukinumab in Cantabria and ASTURias Study. Front Med (Lausanne). 2021;8:679009. PubMed
  8. Ramonda R, Lorenzin M, Carriero A, Chimenti MS, Scarpa R, Marchesoni A et al. Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study. RMD Open. 2021;7(1):. PubMed
  9. Geale K, Lindberg I, Paulsson EC, Wennerström ECM, Tjärnlund A, Noel W et al. Persistence of biologic treatments in psoriatic arthritis: a population-based study in Sweden. Rheumatol Adv Pract. 2020;4(2):rkaa070. PubMed
  10. Torres T, Balato A, Conrad C, Conti A, Dapavo P, Ferreira P et al. Secukinumab drug survival in patients with psoriasis: A multicenter, real-world, retrospective study. J Am Acad Dermatol. 2019;81(1):273-275. PubMed
  11. Daudén E, de Lima GPG, Armesto S, Herrera-Acosta E, Vidal D, Villarasa E et al. Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain. Dermatol Ther (Heidelb). 2021;11(6):2207-2215. PubMed
  12. Kojanova M, Hugo J, Velackova B, Cetkovska P, Fialova J, Dolezal T et al. Efficacy, safety, and drug survival of patients with psoriasis treated with IL-17 inhibitors - brodalumab, ixekizumab, and secukinumab: real-world data from the Czech Republic BIOREP registry. J Dermatolog Treat. 2022;33(6):2827-2837. PubMed
  13. Torres T, Puig L, Vender R, Lynde C, Piaserico S, Carrascosa JM et al. Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study. Am J Clin Dermatol. 2021;22(4):567-579. PubMed
  14. Oh S, Choi S, Yoon HS. Available Alternative Biologics and Disease Groups Influence Biologic Drug Survival in Patients with Psoriasis and Psoriatic Arthritis. Ann Dermatol. 2022;34(5):321-330. PubMed
  15. van der Schoot LS, van den Reek JMPA, Groenewoud JMM, Otero ME, Njoo MD, Ossenkoppele PM et al. Female patients are less satisfied with biological treatment for psoriasis and experience more side-effects than male patients: results from the prospective BioCAPTURE registry. J Eur Acad Dermatol Venereol. 2019;33(10):1913-1920. PubMed
  16. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.] länk

Författare: Hjalmar Wadström

Faktagranskat av: Carl-Olav Stiller, Diana Rydberg

Godkänt av: Karin Schenck-Gustafsson