"Patient-Reported Outcomes", such as the extent of physical impairments or participation in professional and social life, play an increasingly important role in the assessment of drugs. In this respect, monotherapy with Sarilumab is superior to monotherapy with Adalimumab in patients with rheumatoid arthritis (RA) according to data from the MONARCH study.
The interleukin (IL)-6 signaling pathway plays a key role in the pathogenesis and development of clinical manifestations of RA, including pain and fatigue. Such patient-reported outcomes (PROs) have a significant impact on the physical, social, and psychological aspects of the disease and on the daily lives of patients. Quantifying them is therefore essential to fully assess the efficacy of treatment.
Data from the MONARCH Phase III trial are available for direct comparison of monotherapy with the anti-IL-6 antibody sarilumab and the tumor necrosis factor (TNF) alpha inhibitor adalimumab. Included in the study were 369 patients with active RA who did not respond adequately to or did not tolerate methotrexate (MTX) or who were considered unsuitable for MTX therapy. They received 40mg adalimumab or 200mg sarilumab (in combination with the other placebo) every two weeks as subcutaneous injections for 24 weeks.
The primary endpoint was the change in Disease Activity Score 28 (DAS28) with additional consideration of erythrocyte sedimentation rate (DAS28-ESR). In this respect, sarilumab showed a significantly higher clinical efficacy with a decrease of 3.28 points than adalimumab with a decrease of 2.2 points (p<0.0001). With regard to PROs, the following parameters were collected at baseline, week 12 and week 24:
By week 24, all PROs had improved in both treatment groups. However, on many of the scales and subscales, sarilumab showed significantly better efficacy compared to adalimumab, such as the decrease in physical restrictions in HAQ-DI (p<0.005), the overall assessment of disease activity by patients in PtGA (p<0.001), and the decrease in pain intensity (p<0.001).
The same applies to improvements in the physical sum score of SF-36 (p<0.001). In detail, this concerned the domains of physical functioning (p<0.005), physical role function (p<0.05), physical pain (p<0.005) and social functioning (p<0.005). Sarilumab was also significantly superior to RAID score (p<0.001) in terms of morning stiffness (p<0.05), disease impact in RAID score (p<0.001), and overall WPS-RA score improvement (p<0.005). By week 12, comparable differences were already evident. There was no significant difference between the two groups in the mental sum score of SF-36 and fatigue.
A minimal clinically important difference (MCID) in HAQ-DI response to week 24 occurred significantly more frequently in sarilumab with 67.4% of patients than in adalimumab with 54.1% (p<0.01). In the physical sum score of SF-36, corresponding improvements were observed in 62.0% and 47.6% (p<0.001) of patients treated with sarilumab and adalimumab, respectively, in 43.5% and 29.7% (p<0.001) of patients treated with RAID, and in 73.9% and 62.2% of patients treated with sarilumab and adalimumab, respectively, with respect to morning stiffness. In HAQ-DI, FACIT-F and all domains of the SF-36 questionnaire, the proportion of patients with normal values increased significantly in both study arms, with numerically better results for sarilumab.
Monotherapy with sarilumab is superior to monotherapy with adalimumab according to data from the MONARCH study in various PROs, including physical functioning. Improvements were seen in both drugs after 12 weeks. By week 24, however, the difference between the study arms had increased. The PRO analyses thus support the data on the superior clinical efficacy of sarilumab compared to adalimumab. As in other studies with sarilumab and adalimumab, substantial limitations in general health, physical functioning and patient participation in social life were observed at baseline. In both study arms, however, a relevant proportion of patients in different domains achieved values within the normal range, which is, therefore, a realistic goal in RA therapy today. One of the most important therapeutic goals in RA is to mitigate the effects of the disease on patients' lives. According to the data, this is better possible in monotherapy with the anti-IL-6 antibody sarilumab than with the widely used biologic adalimumab.
Source:
Strand V, Gossec L, Proudfoot CWJ et al. Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis. Arthritis Res Ther 2018; 20: 129