Sarilumab and Non-biologic Disease-Modifying Antirheumatic Drugs in Patients with Active RA and Inadequate Response or Intolerance to TNF Inhibitors
In this Phase 3 study (TARGET) of TNF-IR patients, sarilumab plus csDMARD(s) demonstrated clinical efficacy and improvements in physical function versus placebo plus csDMARD(s).
Patients (N=546) were randomised 1:1:1 to sarilumab 150 mg, 200 mg Q2W or placebo (all plus csDMARD[s]). Two co-primary endpoints versus placebo were investigated: ACR20 response rate at Week 24, and HAQ-DI change from baseline at Week 12.
As well as improvements in ACR20 responses (33.7% vs 55.8 and 60.9%, for placebo, sarilumab 150 mg and 200 mg, respectively; P<0.0001), and improvements in HAQ-DI (–0.26 vs –0.46 and –0.47, respectively; P<0.01), both doses showed clinical benefit in multiple secondary endpoints. That sarilumab improved ACR core components including those for assessment of disease activity and pain, shows it provides a clinically meaningful benefit.
Sarilumab was generally well tolerated but treatment discontinuations due to AEs, SAEs and laboratory abnormalities (although consistent with IL-6 blockade) were greater with sarilumab versus placebo. However, serious infections were similar across groups: 1.1%, 0.6%, 1.1%, respectively. Sarilumab showed favourable changes in CRP, albumin, hemoglobin and cholesterol levels.
Overall, these data indicate that sarilumab is effective and generally well tolerated in patients with prior TNFi failure, and support data obtained from MTX-IR patients.