MEASURE 1 Favors Secukinumab for Ankylosing Spondylitis

Secukinumab relieves the clinical signs and symptoms of ankylosing spondylitis at two years, shows a study published in the Annals of the Rheumatic Diseases.

Secukinumab is an interleukin-17A inhibitor that is currently approved for use in adult patients with moderate to severe psoriasis, active psoriatic arthritis and ankylosing spondylitis.

For patients with active ankylosing spondylitis, TNF inhibitors are recommended, but up to 40 percent of patients do not respond to anti-TNF therapy or they cannot tolerate the medication. In addition, TNF inhibitors can lose their efficacy over time. In this study, researchers provide an update on secukinumab for ankylosing spondylitis as shown during the non-controlled continuation phase of MEASURE 1 through two years.

“These results should be viewed in the context of the relatively small number of anti-TNF-IR patients, particularly at week 104, and the heterogeneity of this subpopulation, which comprised patients who failed anti-TNF treatment for any one of several reasons, including lack of primary or secondary efficacy, or intolerance. Overall, given the lack of therapeutic alternatives, these findings indicate that secukinumab may address an unmet clinical need in anti-TNF-IR patients, as well as providing a high level of efficacy as first-line therapy in anti-TNF-naive patients,” wrote researchers who were led by Jürgen Braun of Ruhr-University in Germany.

MEASURE 1 is a randomized, double-blind, placebo-controlled, multicenter study aimed at demonstrating efficacy though 16 weeks and long-term safety, tolerability and efficacy at two years in patients with active ankylosing spondylitis. Ultimately 290 patients were included and completed the study with 97 patients receiving treatments of 150 mg secukinumab intravenous, 103 patients receiving secukinumab 75 mg intravenous, and 90 patients receiving placebo up to 24 weeks.

Efficacy was based on Assessment of SpondyloArthritis International Society 20 and 40 score (ASAS20/40). Based on both scores, response rates for 150mg IV secukinumab at 104 weeks were 73.7%/55.7% and for 75mg IV, 68%/48.5% respectively.

Response rates in patients naive to anti-TNF biologic medicines and those exposed to biologics other than secukinumab with inadequate responses were consistently higher than with the placebo group. Response at 104 weeks for naive patients in the 150 mg and 75 mg groups were 85.5% and 72.3% respectively while response in patients that failed to respond on other anti-TNF drugs were 55.6% and 71.4% on 150 mg and 75 mg respectively.

Preventing further structural damage is a long-term treatment goal in ankylosing spondylitis. But this study does not show that anti-TNF therapy prevents radiographic progression over two years. The mean change in mSASSS (modified Stoke Ankylosing Spondylitis Spine Score) through two years of secukinumab therapy was 0.30 (SD 2.53) overall, and 0.38–0.52 among patients with known predictors of radiographic progression at baseline, such as syndesmophytes or elevated CRP.

Patients who had no syndesmophytes on radiographs at baseline in the secukinumab group remained without them at a rate of 95.3% while 70% of those starting with syndesmophytes so no progression.

No unexpected adverse events were uncovered with the most common events being nasopharyngitis, diarrhea, headache, upper respiratory tract infections and pharyngitis.

The researchers wrote that “long-term controlled studies are needed to evaluate whether secukinumab inhibits the progression of structural manifestations of AS.”

References:

Jürgen Braun, Xenofon Baraliakos, et. al. "Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study," Annals of the Rheumatic Diseases. Published online Dec. 13, 2016. DOI:  10.1136/annrheumdis-2016-209730