Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN)

Abstract

ObjectivesThe ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-α (IL-6Rα), in patients with ankylosing spondylitis (AS).MethodsPatients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease Activity Score, high-sensitivity C-reactive protein (hs-CRP) value, and safety.ResultsBaseline demographic and disease characteristics of the 301 patients enrolled were similar across treatment groups. At week 12, there was no statistically significant difference in ASAS20 response rate between placebo (ASAS20 = 24.0%) and any sarilumab dose group. A significantly greater reduction in hs-CRP value was achieved with the higher sarilumab doses versus placebo. No other statistically significant differences were evident for secondary efficacy endpoints.The most common treatment-emergent adverse events reported for sarilumab included infections (non-serious), neutropenia, and increase in alanine aminotransferase. No cases of tuberculosis, opportunistic, or fungal infections, or bowel perforations were reported. Seven patients experienced a treatment-emergent serious adverse event (all in sarilumab treatment groups). No deaths occurred.ConclusionsThe ALIGN study shows that IL-6Rα blockade with sarilumab was not an effective treatment for AS. Sarilumab was generally well tolerated with a manageable safety profile.

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

“…[29][30][31][32][33] Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the ASAS20 * Plus-minus values are means ±SD. The reporting period for safety data was the period from baseline to the visit at week 52 of the last patient enrolled.…”

Pharmacological therapy of spondyloarthritis

“…Two randomised, double-blind, placebo-controlled studies showed that the anti-IL6 agents tocilizumab and sarilumab are ineffective on AS [114,115].…”

Targeting the interleukin-23/17 axis in axial spondyloarthritis

“…Moreover, up to 50% of patients with active axSpA do not achieve primary endpoints despite treatment with NSAIDs and/or anti-TNF-α blocking agents [56]**. Moreover, recent clinical trials also demonstrated that targeting other cytokines or molecules such as IL-1 [57], IL-6 [58], or enzyme phosphodiesterase 4 (PDE4) [59] are not effective in axSpA. Fortunately, results from clinical trials show that targeting the IL-23/IL-17 pathway holds great promise for treatment of axSpA (Figure 2).…”