Sarilumab, a human monoclonal antibody that inhibits interleukin (IL)-6–mediated signaling by blocking IL-6 receptor alpha, is currently approved for the treatment of moderately to severely active rheumatoid arthritis (RA). In the phase 3 TARGET study, sarilumab (150 or 200 mg) plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) improved RA signs and symptoms and physical function compared with placebo in adults with active, moderate-to-severe RA who were intolerant of, or showed inadequate response to, tumor necrosis factor (TNF) inhibitors. The co-primary end points in the TARGET trial were 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24 and change from baseline in Health Assessment Questionnaire Disability Index at week 12. To address whether patients with higher baseline disease activity are more likely to show response than those with lower baseline disease activity in clinical trials, this post-hoc analysis sought to examine the efficacy of sarilumab in patient subgroups based on median baseline disease activity levels.
This analysis included all patients enrolled in the TARGET study who were randomized to placebo (n = 181), sarilumab 150 mg every 2 weeks (q2w; n = 181), and sarilumab 200 mg q2w (n = 184). Patients were classified into 2 patient subgroups—less or more active disease, based on disease activity at baseline, with the less active group having Disease Activity Score 28–C-reactive protein (DAS28-CRP) <6.2, Clinical Disease Activity Index (CDAI; <42.9; and CRP <17.8) and the more active group having less or the same values in these efficacy parameters. At week 24, 20%/50%/70% improvements in ACR response criteria (ACR20/ACR50/ACR70) and changes in DAS28-CRP, CDAI, and CRP values were evaluated.
Baseline demographics and disease characteristics of patients were balanced among TARGET treatment subgroups in terms of duration of RA and number of previous anti-TNFs. The analysis showed that, compared with placebo, a higher percentage of patients treated with sarilumab achieved ACR20/ACR50/ACR70 responses and had greater improvements in DAS28-CRP, CDAI, and CRP at week 24; this was regardless of disease activity at baseline. However, a more pronounced treatment effect with sarilumab (both 150 mg and 200 mg) was seen in patients with higher baseline disease activity versus those with lower baseline activity. Sarilumab-treated patients with higher baseline disease activity versus the placebo cohort had a greater odds ratio for achieving an ACR20/ACR50/ACR70 response at week 24 and least squares mean change from baseline in DAS28-CRP, CDAI, and CRP at week 24 than those with lower baseline disease activity.
The most commonly reported treatment-emergent adverse event in the TARGET trial was infections, with serious infections occurring in 1.1% of patients receiving placebo, 0.6% of patients receiving sarilumab 150 mg, and 1.1% of patients receiving sarilumab 200 mg.
Overall, the results of this post-hoc analysis of the TARGET study confirmed that patients treated with sarilumab (150 and 200 mg q2w) in combination with csDMARDs achieved greater clinical responses compared with those treated with placebo, which was independent of baseline disease activity; however, patients with higher disease activity at baseline showed a greater sarilumab treatment effect, which is consistent with previous reports from clinical trials that patients with higher disease activity are more likely to have deeper responses than those with lower activity.
Fleischmann R, et al. ACR 2017. Abstract 2470.