The ASCERTAIN trial was a randomized, double-blind, parallel-group, 3-arm safety and tolerability study that evaluated sarilumab (150 mg or 200 mg every 2 weeks [q2w]) versus tocilizumab in patients with rheumatoid arthritis (RA) and inadequate response to, or intolerance of, tumor necrosis factor inhibitors receiving background conventional synthetic disease-modifying antirheumatic drugs. The multicenter, extension EXTEND study assessed the long-term safety of sarilumab. It enrolled patients from 5 trials—ASCERTAIN, MOBILITY, TARGET, ONE, and ACT11575. This post hoc analysis examined efficacy and safety outcomes from patients who completed the ASCERTAIN trial and switched to subcutaneous sarilumab 200 mg q2w.
In this analysis, clinical endpoints assessed were Disease Activity Score 28–C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), and 20%/50%/70% improvement in American College of Rheumatology response criteria (ACR20/ACR50/ACR70). Definitions used as cutoffs for remission and low disease activity (LDA) were DAS28-CRP <2.6 and <3.2, and CDAI ≤2.8 and ≤10.0, respectively. Nonresponders were patients who had not achieved these threshold levels of remission and LDA at enrollment in EXTEND.
A total of 175 patients completed the ASCERTAIN trial; of these, 168 continued into the EXTEND trial: 93 from the tocilizumab group, 37 from the sarilumab 150-mg group, and 38 from the sarilumab 200-mg group.
Improvements in DAS28-CRP and CDAI occurred in patients who were nonresponders on enrollment in EXTEND, defined by DAS28-CRP ≥3.2 and CDAI >10. Importantly, higher proportions of nonresponders switching from tocilizumab or sarilumab 150 mg q2w achieved DAS28-CRP or CDAI remission or LDA at week 24 compared with those who continued to receive sarilumab 200 mg q2w. Of these, the greatest increases were noted in patients who initially received tocilizumab, suggesting that switching tocilizumab nonresponders to sarilumab may have favorable efficacy outcomes. For ACR20/ACR50/ACR70 nonresponders on entry into EXTEND, similar proportions of patients from each of the subgroups achieved an ACR response.
The authors concluded that the efficacy of sarilumab was maintained (sarilumab 200 mg q2w) or improved (sarilumab 150 mg q2w or tocilizumab) in patients who switched or continued into the open-label EXTEND trial after completion of the ASCERTAIN trial.
Source: Emery P, van Hoogstraten H, Jayawardena S, et al. Efficacy of sarilumab in patients with rheumatoid arthritis who previously received sarilumab or tocilizumab. Arthritis Rheumatol. 2017;69(suppl 10). Abstract 2468.