Sarilumab, a human anti–interleukin-6 receptor monoclonal antibody, is approved for the treatment of moderately to severely active rheumatoid arthritis (RA). The ASCERTAIN trial was a 24-week, randomized, double-blind, double-dummy, 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 RA and inadequate response to, or intolerance of, tumor necrosis factor inhibitors receiving background conventional synthetic disease-modifying antirheumatic drugs. The multicenter, uncontrolled, extension EXTEND study assessed the long-term safety of open-label 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 end points 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 individual parameters of remission and LDA at enrollment in EXTEND. Clinical end points were based on all available data as observed and were summarized through week 84 of EXTEND according to the original randomized treatment.
A total of 175 patients (tocilizumab, 96; sarilumab 150 mg, 40; sarilumab 200 mg, 39) 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. After switching to the EXTEND trial, efficacy achieved in the clinical end points of DAS28-CRP and CDAI in the ASCERTAIN trial was maintained through week 60.
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 most common treatment-emergent adverse events in ASCERTAIN were neutropenia, injection-site erythema, and nasopharyngitis, which was consistent with the safety profile previously described. Long-term follow-up of safety data is ongoing.
The authors concluded that the efficacy of sarilumab, as assessed by DAS28-CRP, CDAI, and ACR responses, 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; increased efficacy was seen in all nonresponder categories, with the largest increases occurring in those who initially received tocilizumab or sarilumab 150 mg q2w.
Emery P, et al. ACR 2017. Abstract 2468.