Secukinumab, a fully human monoclonal antibody that selectively targets IL-17A, was the first drug in its class to receive approval for use in patients with ankylosing spondylitis (AS).1,2 Back in 2016, the U.S. Food and Drug Administration (FDA) gave its approval based on positive results shown in the pivotal phase 3 studies, in which 590 patients with AS were recruited under the MEASURE 1 and MEASURE 2 studies.2 A long-term follow-up data from the ongoing extensions of the MEASURE 1 study is now available, and it was presented at the 2018 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting.3-5
MEASURE 1, a 2-year, randomized, placebo-controlled phase 3 study, investigated the efficacy of subcutaneous secukinumab in patients aged ≥18 years with active AS who did not adequately respond to nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 Those who were randomized to secukinumab arm received intravenous loading infusions of secukinumab 10mg/kg at weeks 0, 2, and 4, followed by injections of the subcutaneous formulation (either 75 or 150mg) every 4 weeks.3,4
After the 2-year core period of the study, 274 patients entered the 3-year extension period, consisting of 128 patients in the 150mg group and 146 patients in the 75mg group.3,4 Patients in the extension period included those who were switched from the placebo arm as per study protocol.3,4 The extension period was completed by over 80% of patients who participated in it.3,4 Moreover, 82 patients had their dose escalated from 75mg to 150mg after week 168 of the study.3,4
Assessments at week 260 included improvements of Assessment of SpondyloArthritis International Society (ASAS) scores such as ASAS20, ASAS40, and ASAS5/6.3,4 Other efficacy outcomes were also reported as observed. Safety was reported for patients who received at least 1 dose of secukinumab.3,4
Across the 5-year period, the investigators reported a sustained efficacy across multiple domains of AS including signs and symptoms, physical function, and objective markers of inflammation.3,4 These positive results were shown for both dosage groups of secukinumab, but intriguingly, improved responses were reported for patients in the dose-escalation cohort.3,4
Based on patients with data up to 72 weeks after escalating secukinumab dose to 150mg, improvements in ASAS20 (from 74.4% to 82.4%), ASAS40 (from 51.2% to 61.8%), ASAS partial remission (from 15.9% to 17.6%), ASAS5/6 (from 56.1% to 73.5%), and BASDAI50 (Bath Ankylosing Spondylitis Disease Activity Index 50; from 51.2% to 58.8%) were reported.3,4 “That tells me we are at exactly the right dose with 150mg,” said Dr. Xenofon Baraliakos of the Rheumazentrum Ruhrgebiet and Ruhr University Bochum in Herne, Germany.5
The safety profile of secukinumab was consistent with those reported in previous studies, and no new safety signals were identified through 5 years.3,4 The exposure-adjusted incidence rate (EAIR) per 100 patient-years for selected adverse events of interest were 0.1 for ulcerative colitis, 0.6 for Crohn’s disease, 1.8 for uveitis, and 0.5 for malignant/unspecified tumors.3,4
Commenting on the long-term follow-up data of MEASURE 1, as well as another study (FUTURE 1) that assessed secukinumab in patients with psoriatic arthritis (PsA), Professor Georg A. Schett of the University of Erlangen-Nuremberg, Germany, said that “the presentation of long-term data in PsA and AS supports the central role of [secukinumab] in the long-term sustained management of these complex and multi-faceted conditions.”3
1. Blair HA, Dhillon S. Secukinumab: A Review in Ankylosing Spondylitis. Drugs. 2016;76(10):1023-30.
2. Novartis receives two new FDA approvals for Cosentyx to treat patients with ankylosing spondylitis and psoriatic arthritis in the US. Novartis Media Releases. 2018 (Accessed October 31, 2018, at https://www.novartis.com/news/media-releases/novartis-receives-two-new-fda-approvals-cosentyx-treat-patients-ankylosing).
3. Novartis 5-year data in psoriatic arthritis and ankylosing spondylitis reinforces Cosentyx® leadership in spondyloarthritis. Novartis Media Releases. 2018 (Accessed October 31, at https://www.novartis.com/news/media-releases/novartis-5-year-data-psoriatic-arthritis-and-ankylosing-spondylitis-reinforces-cosentyx-leadership-spondyloarthritis).
4. Marzo-Ortega H, Sieper J, Kivitz A, et al. Secukinumab 150 mg Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis with Consistent Safety Profile and High Retention Rate: 4-year Results from a Phase III Trial. Poster presented at 2018 ACR/ARHP Annual Meeting. October 19-24, 2018; Chicago, IL, US. Poster #2556.
5. Long-term Secukinumab Effective for Ankylosing Spondylitis. Medscape. 2018 (Accessed November 2, 2018, at https://www.medscape.com/viewarticle/904022#vp_1).