Comparing Sarilumab monotherapy and Adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH)
The results from the study showed that Sarilumab monotherapy holds superior efficacy and tolerability over Adalimumab monotherapy especially for that rheumatoid arthritis (RA) patients who are unable to continue MTX treatment
For rheumatoid arthritis (RA) patients, biological disease-modifying antirheumatic drugs (bDMARDs) aiming inflammatory cytokines, such as tumor necrosis factor α (TNF-α) or interleukin 6 (IL-6) via the IL-6 receptor (IL-6R), have extended the treatment choices.
For rheumatoid arthritis (RA) patients, biological disease-modifying antirheumatic drugs (bDMARDs) aiming inflammatory cytokines, such as tumor necrosis factor α (TNF-α) or interleukin 6 (IL-6) via the IL-6 receptor (IL-6R), have extended the treatment choices. The data from research studies have confirmed that patients with inadequate response to traditional synthetic DMARDs like methotrexate (MTX) get help from biological DMARDs, resulting in the improved preservation of joint structure and function. However, only one-third of patients with RA use biologics as monotherapy due to MTX intolerance or contraindication. Also, the data from real-world medical practice and prescription drug registries show that bDMARDs are frequently used as monotherapy, either because of physician inclination or due to patient preference. The extensive use of bDMARD monotherapy demands more related data to support the better selection of approved bDMARDs in clinical practice. The effective treatment of RA lies in targeting the IL-6R as it plays a central role in facilitating the underlying disease pathophysiology and clinical manifestations of RA.
Sarilumab is a human IgG1 monoclonal antibody that binds particularly to both soluble and membrane-bound IL-6Rs and inhibits IL-6-mediated signaling through these receptors. In previous studies, Sarilumab was found to be effective in several patients with RA, including MTX inadequate responders and those with an inadequate response or intolerance to TNF inhibitors. Adalimumab is a globally approved bDMARD targeting TNF-α, recommended for use in patients who fail to achieve clinical remission with conventional synthetic DMARDs csDMARDs including MTX. Adalimumab is an approved monotherapy for patients not able to take csDMARDs due to intolerance or contraindication.
Rationale behind research
Data comparing the performance of biological monotherapy is limited. This study has been conducted to cater the unmet need for lack of data comparing the performance of biological monotherapy. This study will also help in describing tactics for the selection and optimal sequencing of available drugs suited for real-world clinical practice.
To examine the effectiveness and safety of Sarilumab and Adalimumab monotherapy in patients with active RA who were unable to continue MTX treatment due to intolerance or inadequate response.
- Primary outcomes: The primary efficacy endpoint was defined as the change from baseline in DAS28-ESR
- Secondary outcomes: The secondary efficacy endpoints were DAS28-ESR remission (<2.6); the Health Assessment Questionnaire-Disability Index (HAQ-DI); ACR 20% (ACR20), 50% (ACR50) and 70% (ACR70) responses; Medical Outcomes Short Form 36 Health Survey (V.2) (SF-36) physical component summary (PCS) score and mental component summary (MCS) score and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
- Adverse events: Safety assessments included incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs)
Time Points: Baseline and at week 24
Baseline characteristics: There were no significant differences in the baseline characteristics between study groups
Primary Outcomes: The mean change in DAS28-ESR from baseline to week 24 was greater in Sarilumab 200 mg q2w as compared to Adalimumab 40 mg q2w (−3.28 vs. −2.20).
Figure 1: Comparison of DAS28-ESR between Adalimumab and Sarilumab (Primary efficacy endpoint) at week 24
- Improvement in DAS28-ESR was greater in the Sarilumab group as compared to Adalimumab group (−2.77 vs. −1.88) by week 12
- The number of patients who achieved an ACR20/50/70 response at week 24 was significantly higher in the Sarilumab group (71.7%/45.7%/23.4%) than the Adalimumab group (58.4%/29.7%/11.9%)
- The mean improvement in HAQ-DI score from baseline to week 24 was considerably higher in the Sarilumab group as compared to the Adalimumab group (−0.61 vs. −0.43)
- At week 24, Sarilumab-treated patients had significantly greater improvement in the SF-36 PCS compared with Adalimumab-treated patients and improvements were observed as early as week 12. Both groups demonstrated similar improvement in SF-36 MCS at week 24.
- Improvement from baseline to week 24 in FACIT-F score was observed in both groups, with a trend towards greater improvement in the Sarilumab group
- Patients receiving Sarilumab had a lower mean CDAI score at weeks 12 and 24 compared to the patients taking Adalimumab (week 24: −28.9 vs. −25.2;)
Adverse events: In both the groups, the incidence of AEs (∼64%, both groups) and SAEs (Adalimumab, 12 (6.5%) vs Sarilumab, 9 (4.9%)) and the rate of discontinuations (Adalimumab, 13 (7.1%) vs Sarilumab, 11 (6.0%)) were similar.
In MONARCH study, Sarilumab was found to be superior to Adalimumab in reducing disease activity and improving the signs and symptoms of RA, as shown by a significant reduction in DAS28-ESR. From the patient’s perspective, the most important benefits of RA treatment are to improve functional disability, pain, and fatigue. Patients receiving Sarilumab showed considerable improvement in their health status as indicated by differences in SF-36 PCS, HAQ-DI, and pain visual analog scale scores, along with a trend towards greater improvement in fatigue.
Overall, the safety and tolerability of Sarilumab are consistent across studies and comparable with the therapeutic targeting of the IL-6 pathway. Further, the results from the study show that Sarilumab improves signs, symptoms and physical functions of RA and is a relevant, powerful and superior monotherapy compared with TNF-α inhibition for patients who are unfit for prolonged treatment with MTX due to intolerance or inadequate response.