Sarilumab, a human monoclonal anti–interleukin-6 receptor alpha antibody, has demonstrated efficacy and safety as monotherapy and combination therapy in clinical trials. The MONARCH trial results showed that subcutaneous sarilumab (200 mg every 2 weeks [q2w]) monotherapy for 24 weeks was superior to adalimumab (40 mg) monotherapy in reducing disease activity and improving physical function in adult patients with active rheumatoid arthritis (RA) who are intolerant of, inappropriate for, or inadequate responders to, methotrexate. Patients who completed the initial double-blind phase in MONARCH continued to the open-label extension and received sarilumab 200-mg-q2w monotherapy. This analysis evaluated the sustainability of clinical responses and improvements in physical function achieved on MONARCH at week 24 with continued sarilumab monotherapy, and assessed disease activity, physical function, and safety in patients switching from adalimumab monotherapy to sarilumab monotherapy.
In this analysis, the sustainability of response was measured for the following clinical efficacy end points: Health Assessment Questionnaire Disability Index (HAQ-DI) ≥0.3 units of improvement, Simple Disease Activity Index (SDAI) ≤3.3 remission, Disease Activity Score 28‒erythrocyte sedimentation rate (DAS28-ESR) <2.6 (remission), <3.2 (low disease activity [LDA]), DAS28–C-reactive protein (DAS28-CRP) <2.6 (remission), <3.2 (LDA), and 20%/50%/70% improvement in American College of Rheumatology (ACR) improvement criteria (ACR20/ACR50/ACR70) responses.
Of the 321 patients who completed the MONARCH study, 320 entered the open-label extension; of these, 155 patients switched from adalimumab to sarilumab (switch group), and 165 remained on sarilumab (continuation group). At open-label extension entry, mean DAS28-ESR was 4.46 and 3.45 in the switch and continuation groups, respectively (P <.0001), and DAS28-ESR ≤3.2 was 16.1% and 47.9%, respectively (P <.0001); in comparison, DAS28-ESR was 6.8 in both treatment groups.
By week 24 of the open-label extension study, clinical efficacy was sustained in both the switch and continuous groups; 49.7% and 58.8% of patients in the switch and continuation groups achieved LDA of DAS28-ESR ≤3.2 (odds ratio [OR], 1.44; P = .1033), 40.0% and 42.4% achieved DAS28-ESR <2.6 remission (OR, 1.11; P = .6586), 12.3% and 18.8% achieved CDAI remission (OR, 1.67; P = .1054), respectively; 63.9% and 66.7% achieved improvement in HAQ-DI ≥0.3 (OR, 1.13; P = .6004), respectively; and 14.8% and 22.4% (OR, 1.66) achieved SDAI remission.
At week 24 of the MONARCH open-label extension, treatment-emergent adverse events (TEAEs) in the switch and continuation groups were 63.9% and 57.9%, respectively; serious TEAEs were 9.0% and 1.2%, respectively; infections were 34.2% and 23.6%, respectively; and serious infections were 1.9% and 0%, respectively, with 1 death in the switch group (malignancy) and no deaths in the continuation group. Discontinuations due to TEAEs occurred in 5.8% of patients in the switch group and 3.6% in the continuation group.
In the open-label extension phase of the phase 3 MONARCH trial, patients switching from adalimumab 40-mg-q2w monotherapy to open-label sarilumab 200-mg-q2w monotherapy demonstrated improvements in RA signs and symptoms and physical function, which became numerically similar to patients who were initially randomized to sarilumab 200 mg q2w.
Burmester GR, et al. ACR 2017. Abstract 2482.