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For the second time, an interleukin-6 receptor-α inhibitor has proven no better than placebo against ankylosing spondylitis in a randomized trial. The highest dose of sarilumab was most effective, but not effective enough to pass muster.
Sieper J, Braun J, Kay J, et al., Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN).Ann Rheum Dis doi:10.1136/annrheumdis-2013-204963. (Open Access)
Sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-Î± (IL-6RÎ±), delivered disappointing initial results against active ankylosing spondylitis (AS) in a multinational clinical trial. It proved generally well-tolerated, but not effective.
In the ALIGN study, investigators randomized 301 patients with active AS despite conventional treatment to receive one of five subcutaneous regimens of the drug or a placebo (100 or 150 mg weekly or 100, 150, or 200 mg every other week), and followed them for 12 weeks.
No treatment regimen significantly improved upon the placebo response rate of 24%, judged by the Axial SpondyloArthritis international Society (ASAS) 20 response criteria. The treatment group with the highest dosage (150 mg) did show a greater effect, but it was still not significantly better than placebo.
Higher doses also yielded greater reductions in high-sensitivity C-reactive protein (hs-CPR) than placebo, but there were no significant differences in secondary endpoints.
The overall safety profile was judged "manageable," although 39 patients withdrew from the study, mostly due to treatment-emergency adverse events such as infections or neutropenia and to lack of efficacy.
Is this the death knell for IL-6RÎ± blockade in AS? The investigators note that a similar study testing another drug with this mechanism, tocilizumab, produced similarly disheartening results. The authors say this demonstrates that promising case reports or other preclinical evidence may not prove out for a targeted drug in a disease, like AS, of unclear etiology.
Sarilumab has shown efficacy against rheumatoid arthritis in other trials.