Background/Purpose: Sarilumab is a human mAb blocking the IL-6Rα. In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg subcutaneously every 2 weeks [q2w]) plus conventional synthetic (cs)DMARDs demonstrated efficacy in adults with active, moderate‑to-severe RA and intolerance of or inadequate response to TNF inhibitors. The most common treatment-emergent adverse events in TARGET were infections, neutropenia, injection site reactions, increased lipids, and increased transaminases. It has been postulated that, in clinical trials, patients with higher baseline disease activity are more likely to show response than those with lower baseline disease activity.¹ The objective of this post hoc analysis was to examine the efficacy of sarilumab in patient subgroups based on median baseline disease activity levels.

Methods: All patients in the TARGET study randomized to placebo (n=181), sarilumab 150 mg q2w (n=181), and sarilumab 200 mg q2w (n=184) were included. Disease activity at baseline was defined according to < or ≥ median levels (DAS28-CRP: 6.2, clinical disease activity index [CDAI]: 42.9, and CRP: 17.8). ACR20/50/70 response rates and changes in DAS28-CRP, CDAI, and CRP values were evaluated at week 24. Nominal P values were assessed using the Cochran-Mantel-Haenszel test for binary endpoints and mixed model with repeated measures for continuous endpoints.

Results: Regardless of disease activity at baseline, a higher percentage of patients treated with sarilumab vs placebo achieved ACR20/50/70 responses and had greater improvements in DAS28-CRP, CDAI, and CRP at week 24 (Table). Placebo-adjusted treatment effect with sarilumab was more pronounced in patients with higher baseline disease activity, with lower responses seen with placebo in these patients (data not shown). The odds ratio vs placebo for achieving an ACR20/50/70 response at week 24 was greater in sarilumab-treated patients with higher baseline disease activity than in those with lower baseline disease activity for each definition assessed. Likewise, change from baseline in DAS28-CRP, CDAI, and CRP at week 24 were greater in sarilumab-treated patients with higher baseline disease activity for each definition assessed.

Conclusion: Patients treated with sarilumab 150 and 200 mg q2w plus csDMARDs achieved greater clinical responses vs those treated with placebo, regardless of disease activity at baseline. The treatment effect of sarilumab was larger in patients with higher disease activity at baseline.

Reference:

1. Aletaha et al. Ann Rheum Dis. 2008;67:1360-1364.