Artikel
Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis: 2-year results from a phase 3 trial with subcutaneous loading and maintenance dosing (MEASURE 2)
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Veröffentlicht: | 29. August 2016 |
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Gliederung
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Background: Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks (wks) in the randomised, double-blind, placebo (PBO)-controlled, Phase 3 MEASURE 2 study (NCT01649375) [1].
Objectives: To evaluate the long-term (104 wks) efficacy and safety of secukinumab in MEASURE 2 study.
Methods: 219 subjects with active AS, classified by modified New York criteria, despite therapy with NSAIDs, were randomised to subcutaneous (s.c.) secukinumab 150 or 75 mg or PBO at baseline (BL), Wks 1, 2 and 3, and every 4 wks (q4w) from Wk 4. At Wk 16, PBO-treated subjects were re-randomised to secukinumab 150 or 75 mg s.c. q4w. At BL, 39% of subjects had an inadequate response/intolerance to prior anti-TNF therapy (anti–TNF-IR). Primary endpoint was ASAS20 response rates at Wk 16. Secondary endpoints included ASAS40, hsCRP, ASAS5/6, BASDAI, SF-36 PCS and ASAS partial remission. Endpoints were assessed through Wk 104, with multiple imputation for binary variables and a mixed-model repeated measures for continuous variables. Analyses stratified by anti-TNF history were pre-specified and are reported as observed.
Results: 60/72 (83.3%), 57/73 (78.1%) and 57/74 (77%) subjects completed 104 wks of treatment with secukinumab 150 mg, 75 mg and PBO, respectively. As reported previously, secukinumab 150 mg significantly improved all pre-specified endpoints at Wk 16 vs. PBO, except ASAS partial remission; the 75 mg dose did not reach statistical significance at Wk 16 based on hierarchical testing [1]. ASAS20/40 response rates at Wk 104 were 71.5/47.5% with both secukinumab doses. Clinical improvements with secukinumab were sustained through Wk 104 across all secondary endpoints (Table 1 [Tab. 1]). In the subgroup of anti–TNF-naïve subjects, ASAS20/40 response rates at Wk 104 (observed data) were 76.9/56.4% and 80.0/60.0% with secukinumab 150 mg and 75 mg, respectively; corresponding rates in anti–TNF-IR subjects were 85.0/50.0% and 68.8/43.8%. Across the treatment period (mean secukinumab exposure: 735.6 days), exposure-adjusted incidence rates for serious infections/infestations, IBD, malignant/unspecified tumours and MACE with secukinumab were 1.2, 1.4, 0.5 and 0.7 per 100 subject-years, respectively. No cases of TB, opportunistic infectionsor suicidality-related AEs were reported.
Conclusion: Secukinumab provided sustained improvement through 2 years in the signs and symptoms of AS with improved physical function, regardless of anti-TNF status. Safety was consistent with previous reports.
References
- 1.
- Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, Deodhar A, Porter B, Martin R, Andersson M, Mpofu S, Richards HB; MEASURE 1 Study Group; MEASURE 2 Study Group. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015 Dec 24;373(26):2534-48. DOI: 10.1056/NEJMoa1505066