Positive Results for Phase 3 Clinical Trial of Sarilumab

Among some of the exciting data presented at the 2014 European League Against Rheumatism Annual Congress (EULAR), were positive results from the phase 3 randomized SARIL-RA-MOBILITY trial of the investigational drug sarilumab.1,2 Sarilumab is the first fully-human monoclonal antibody directed against the IL-6 receptor. It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling.

SARIL-RA-MOBILITY included 1,197 adult patients with active, moderate-to-severe rheumatoid arthritis (RA) who were did not responding adequately to methotrexate. Patients in the study received sarilumab 150 mg, sarilumab 200 mg or placebo given subcutaneously every other week. All study patients also received concurrent methotrexate treatment while participating in the trial. The 3 co-primary endpoints for the study were: improved clinical response for at least 24 weeks (measured by the American College of Rheumatology score of 20 percent improvement [ACR20]), improved function at 16 weeks (measured by Health Assessment Questionnaire – Disability Index [HAQ-DI]), and persistent relief of symptoms and suspension of joint damage at 52 weeks (measured by change in the van der Heijde modified total Sharp score [mTSS]).

For each of the 3 co-primary endpoints, both groups receiving sarilumab treatment demonstrated significant improvements compared with placebo (P<0.0001). At 24 weeks, patients receiving sarilumab 150 mg experienced a 58% improvement in ACR20, while patients receiving sarilumab 200 mg and patients receiving placebo had a 66% and 33% improvement, respectively. HAQ-DI scores were -0.53, -0.55, and -0.29 in the sarilumab 150 mg, sarilumab 200 mg, and placebo groups respectively. Results for mTSS scores were 0.90, 0.25, and 2.78 in the sarilumab 150 mg, sarilumab 200 mg, and placebo groups respectively. Additionally, patients receiving sarilumab showed improvement in major clinical response, which was defined as a 70% or greater reduction in signs and symptoms of RA, as measured by improvement of the ACR70 response, for at least 24 consecutive weeks.

A greater incidence of treatment-emergent adverse events leading to withdrawal was evident in both sarilumab treatment groups (12.5% for the 150 mg, group; 13.9% for the 200 mg group) compared to placebo (4.7%). The most frequently reported adverse event was infections; infections occurred more frequently in the sarilumab groups compared to placebo.

There are currently 6 ongoing Phase 3 clinical studies of sarilumab and targeted enrollment is approximately 2,800 patients with RA.

These preliminary Phase 3 data for sarilumab are promising, and if this drug is eventually approved for use in patients with RA, it could be a valuable addition to the RA treatment armamentarium.

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