The online version of this article (doi:10.1186/s13075-017-1490-y) contains supplementary material, which is available to authorized users.
Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen.
A total of 226 patients were randomized to intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables.
The primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P < 0.01) and IV-150 mg (58.1%; P < 0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3–4 neutropenia were 1.8% for both of these adverse events in secukinumab-treated patients.
Secukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings.
ClinicalTrials.gov, NCT02008916. Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.
Additional file 1: Study design. Randomization was stratified according to whether patients were anti-TNF-naïve or had previous inadequate response or intolerance to anti-TNF therapy. ASAS, Assessment of SpondyloArthritis international Society; ASAS20, 20% improvement in ASAS criteria; BL, baseline; i.v., intravenous; q4wk, every 4 weeks; PBO, placebo; R, randomization; s.c., subcutaneous; TNF, tumor necrosis factor; wk, week. (PDF 817 kb)
Additional file 2: Efficacy endpoints at week 52 using non-responder imputation and observed data. (DOCX 16 kb)
Additional file 3: Efficacy endpoints at week 52 for placebo patients re-randomized to secukinumab using non-responder imputation and observed data. (DOCX 16 kb)
Additional file 4: SIOQ domain scores over week 16. Overall patient experience with secukinumab administration via the pre-filled syringes was assessed over time from baseline (PRE module) to week 16 (POST modules) by SIAQ domains: (a) feeling about self-injection; (b) self-confidence and (c) satisfaction with self-injection. SIAQ, Self-Injection Assessment Questionnaire. (PDF 781 kb)
Additional file 5: List of Independent Ethics Committees (IECs) or Institutional Review Boards (IRBs) that approved study. (DOCX 19 kb)
Boonen A, van der Linden SM. The burden of ankylosing spondylitis. J Rheumatol Suppl. 2006;78:4–11. PubMed
Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014;53(4):650–7. CrossRef
Van Lümig PPM, Lecluse LLA, Driessen RJB, Spuls PI, Boezeman JB, Van De Kerkhof PCM, De Jong EMGJ. Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure, secondary failure or intolerance to etanercept. Br J Dermatol. 2010;163(4):838–46. CrossRefPubMed
Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, McInnes I, van Laar JM, Landewe R, Wordsworth P, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9906):1705–13. CrossRefPubMed
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewe R, Conaghan PG, Gottlieb AB, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;386(9999):1137–46. CrossRefPubMed
McInnes IB, Sieper J, Braun J, Emery P, van der Heijde D, Isaacs JD, Dahmen G, Wollenhaupt J, Schulze-Koops H, Kogan J, et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis. 2014;73(2):349–56. CrossRefPubMed
Gottlieb AB, Blauvelt A, Prinz JC, Papanastasiou P, Pathan R, Nyirady J, Fox T, Papavassilis C. Secukinumab self-administration by prefilled syringe maintains reduction of plaque psoriasis severity over 52 weeks: results of the FEATURE trial. J Drugs Dermatol. 2016;15(10):1226–34. PubMed
HUMIRA: Highlights of prescribing information. [ http://www.rxabbvie.com/pdf/humira.pdf]. Accessed 21 Nov 2016.
ENBREL: Highlights of prescribing information. [ http://pi.amgen.com/united_states/enbrel/derm/enbrel_pi.pdf]. Accessed 21 Nov 2016.
- Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II