Sarilumab bests adalimumab in improving PROs in methotrexate-intolerant RA patients
Patients with active rheumatoid arthritis (RA) who had inadequate response or intolerance to methotrexate had better patient-reported outcomes (PROs) with the anti-interleukin-6 receptor monoclonal antibody sarilumab compared with the widely used biologic disease-modifying antirheumatic drug (bDMARD) adalimumab, translating to an improved general health status, physical function, and participation, the MONARCH* study showed.
At week 24, significant between-group differences were seen among sarilumab vs adalimumab recipients in terms of HAQ-DI** (least-squares mean change [LSM], -0.18; p<0.005), PtGA*** (LSM, -8.48; p<0.001), and pain Visual Analogue Score (VAS; LSM, -8.78; p<0.001). SF-36# Physical Component Summary was also improved (LSM, 2.65; p<0.001), particularly in the domains of physical functioning (LSM, 7.37; p<0.005), role physical (LSM, 4.57; p<0.050), bodily pain (LSM, 6.28; p<0.005), and social functioning (LSM, 6.37; p<0.050). [Arthritis Res Ther 2018;doi:10.1186/s13075-018-1614-z]
The significant improvement in the relatively new disease-specific parameter
RAID## with sarilumab vs adalimumab (LSM, -0.78;
p<0.001) underscored the broad benefits of sarilumab monotherapy in RA, said the researchers, noting greater numerical improvement in the fatigue domain, a key consideration for patients with active RA.
Another notable outcome is the improved morning stiffness VAS among sarilumab vs adalimumab recipients (LSM, -5.80; p<0.050), as morning stiffness may substantially affect patients and result in frustration, distress, and absenteeism. [Scand J Rheumatol Suppl 2011;125:6-11]
Global WPS-RA### was also significantly improved (p<0.005), particularly in the number of housework days missed (LSM, -1.28; p<0.050), number of days wherein household productivity was reduced by ≥50 percent (LSM, -1.83; p<0.005), and the rate by which RA interferes with household productivity (LSM, -0.66; p<0.050).
However, the numerical between-group differences in the elements pertaining to work outside the home were small, considering the fraction of employed participants (40 percent), which may be a potential limitation, the researchers pointed out.
“[Taken together], quantifying fatigue [and] the effect of RA symptoms on participation … and on broad health status or health-related quality of life [are] vital for a comprehensive evaluation of RA treatments such as sarilumab,” they said.
These findings were established after randomizing 369 participants (mean age 52.2 years, 83 percent female) 1:1 to receive either sarilumab 200 mg or adalimumab 40 mg every 2 weeks, in addition to placebo, for 24 weeks. Considerable improvements were evident at week 12 and increased over time, despite dose escalation to weekly adalimumab or matching placebo among poor responders at week 16, noted the researchers.
Despite the numerically greater increases with sarilumab, it is important to note that the fraction of patients reporting normative values in HAQ-DI, Functional Assessment of Chronic Illness Therapy-Fatigue, and SF-36 Physical and Mental Component Summary, as well as all individual SF-36 domains, increased with both regimens, said the researchers. “These data indicate that attainment of normative values is now a reasonable goal for RA therapy.”
Overall, the greater improvement across multiple PROs with sarilumab underlines the importance of bDMARD monotherapy as a therapeutic alternative to conventional synthetic DMARDs, given the associated adverse events particularly with methotrexate. [Clin Rheumatol 2014;33:609-614; Ann Rheum Dis 2011;70:583-589]
The results supplement physician-reported clinical assessments and offer a more comprehensive understanding of RA and the impact of RA treatment on patients, said the researchers. “Using the American College of Rheumatology core dataset alone to define disease activity and treatment benefit does not account for other disease symptoms important to patients with RA or for the significant physical, social, and psychological impacts of RA on a patient’s daily life and functioning.”
“[The wide range of PROs evaluated] offered a means to obtain these data in a clinically meaningful way [and allowed us] to understand the level of benefit observed from a patient perspective,” they said.