FDA Approves Secukinumab (Cosentyx) for Ankylosing Spondylitis and Psoriatic Arthritis

The US Food and Drug Administration (FDA) has approved secukinumab (Cosentyx; Novartis) for the treatment of adults with active ankylosing spondylitis (AS) and active psoriatic arthritis (PsA).

Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.

Secukinumab was first approved for the treatment of moderate to severe psoriasis in January 2015 following the results of two phase 3 placebo-controlled trials (ERASURE and FIXTURE).

The approvals are based on the efficacy and safety outcomes from 2 AS and 2 PsA placebo-controlled phase 3 studies that included more than 1500 adult patients with either condition who were either biologic treatment naive or who had an inadequate treatment response or intolerance to tumor ;necrosis factor (TNF) inhibitors. The researchers report that treatment with secukinumab resulted in statistically significant improvements in the signs and symptoms of AS and PsA as compared to placebo, as measured by a minimum of 20% improvement in the Assessment of Spondyloarthritis International Society criteria (ASAS20) at week 16 and a 20% reduction in the American College of Rheumatology (ACR20) response criteria at week 24, respectively.

ASAS20 and ACR20 are standardized tools used to assess clinical improvement in AS and PsA.  ASAS20  is defined as an improvement of at least 20% and an absolute improvement of at least 10 units on a 0 to 100-mm scale in at least 3 of the following:

• Patient global assessment measured on a visual analog scale with extremes labeled “none” and “severe”;
• Pain assessment represented by the average of total and nocturnal pain scores, both measured on VAS with extremes labeled “no pain” and “most severe pain”;
• Function represented by the Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by VAS with extremes labeled “easy” and “impossible”; and
• Morning stiffness, represented by the average of the last 2 questions on the 6-question Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) regarding morning stiffness as measured by VAS (one with extremes labelled “none” and “very severe” and the other marking duration of morning stiffness between “0” and “2 or more hours” ).

The ACR 20 is defined as an improvement of at least 20% comparing disease activity as 2 discrete time points in at least 3 of the following parameters:  patient assessment, physician assessment, pain scale, disability/functional questionnaire, and the measurable decrease in either the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level.

Summary and Clinical Applicability

Secukinumab has been shown to be effective in the treatment of AS and PsA as measured by the ASAS20 and ACR20 scales. Its adverse effect profile when used in the treatment of AS and PsA remains similar to that seen when used to treat plaque psoriasis.

References

1. Baeten D, Sieper J, Braun J, et al; MEASURE 1 Study Group; MEASURE 2 Study Group.  Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373(26):2534-2548. doi: 10.1056/NEJMoa1505066.

2. Ramiro S, Smolen JS, Landewé R, et al. Pharmacological treatment of psoriatic arthritis: a systematic literature review for the 2015 update of the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis. 2015; Dec 11. pii: annrheumdis-2015-208466. doi: 10.1136/annrheumdis-2015-208466. [Epub ahead of print]