Subscribe or Manage Preferences

Sarilumab + csDMARDs Effective Regardless of Baseline Disease Activity in RA Patients with Inadequate Response to TNF Inhibitors

Rheumatology Practice Management December 2017 Vol 5 No 5 - ACR 2017 Conference Correspondent, Rheumatoid Arthritis

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.

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 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.

These results 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.

Source: Fleischmann R, van Hoogstraten H, Jayawardena S, et al. Efficacy of sarilumab in combination with Csdmards in patients with rheumatoid arthritis and inadequate response to TNF inhibitors by baseline levels of disease activity. Arthritis Rheumatol. 2017;69(suppl 10). Abstract 2470.

Related Items
Efficacy and Safety of Switching from Adalimumab to Sarilumab
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Sustained Response in TARGET Study of Sarilumab + csDMARDs versus Placebo in RA Patients with Inadequate Response to TNF Inhibitors
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Highly Sensitive Cardiac Troponin I Levels in Peripheral Blood Predict CV Events in Patients with RA
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
An Updated Integrated Safety Analysis of Baricitinib for the Treatment of Moderate-to-Severe RA
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Upadacitinib Is Effective in Patients with Active RA with Inadequate Response to Conventional Synthetic DMARDs
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Cost per Response for Abatacept versus Adalimumab in Patients with Seropositive, Erosive Early RA
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Sarilumab Efficacy Maintained or Improved in Previously Treated Patients with RA
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Long-Term Efficacy and Safety Results of SIRROUND-D Trial of Sirukumab in Patients with Active RA Despite DMARD Treatment
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Longer Duration of Response in MOBILITY Study with Sarilumab plus MTX in Patients with Active, Moderate-to-Severe RA
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Tofacitinib with and without MTX and Adalimumab with MTX Improves PROs in Patients with RA
Rheumatology Practice Management December 2017 Vol 5 No 5 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Last modified: January 15, 2018
  • American Health and Drug Benefits
  • Lynx CME
  • Value Based Care in Rheumatology
  • Oncology Practice Management
  • Urology Practice Management

Search