Efficacy Lies in Both Sarilumab and Methotrexate in RA

Improvements compared with placebo were significant for sarilumab and conventional synthetic DMARDs in adults with active, moderate-to-severe rheumatoid arthritis and those who had inadequate responses or intolerance with one or more TNF inhibitors, new research shows.

Sarilumab is an investigational human monoclonal antibody directed against the interleukin 6 receptor. Prior research has shown sarilumab and methotrexate to be both efficacious and safe in patients with active and moderate-to-severe rheumatoid arthritis, according to Roy Fleischmann, MD, of Metroplex Clinical Research Center  in Dallas, during a presentation given at the 2015 ACR/ARHP annual meeting in San Francisco, Calif., on Nov. 8.

“How do you put this together? I would prefer to use 200 mg sarilumab plus methotrexate, because that’s where the efficacy is. Later, if a patient does have an adverse event, I would reduce sarilumab to 150 mg,” Dr. Fleishman said.

Dr. Fleischmann’s TARGET study included 546 patients randomized 1:1:1 to sarilumab 200 or 150 mg q2w with csDMARDs or placebo q2w with csDMARDs for 24 weeks.

The primary endpoints were ACR20 responses at 24 weeks and change from baseline in HAQ-DI at 12 weeks. ACR20 response rates were significantly greater for the sarilumab 150 and 200 mg and csDMARD groups at 55.8% and 60.9%, respectively, compared with 33.7% for placebo (P<0.0001). Similarly, HAQ-DI score improvement of -0.5 for each sarilumab dose and csDMARD was greater than the -0.3 improvement with placebo (P=0.0007/P=0.0004, respectively).

Treatment emergent adverse events (TEAEs) were more common in the sarilumab groups, with overall rates of 49.7% for placebo and 65.7% and 65.2% for the 150 mg and 200 mg sarilumab with csDMARD groups, respectively.

Discontinuation rates, however, were low for all groups (4.4% placebo, 7.7% and 9.2% for the respective sarilumab and csDMARD groups).

While neutropenia was most common among TEAES, serious infections were infrequent and similar for all groups. Also, closer analysis revealed slightly better efficacy for the 200 mg dose and better safety for the 150 mg dose.

References:

Abstract 970 -

"Efficacy and Safety of Sarilumab in Combination with Csdmards in Patients with Active Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant of Anti–TNF-α Therapy: Results from a Phase 3 Study," 

Roy Fleischmann MD. ACR/ARHP 2015.