The Effects of Disease Modifying Anti-Rheumatic Drugs (DMARDs) on Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Network Meta-Analyses
Author(s)
Luuk van Esveld, PharmD1, Marijke van den Dikkenberg, MSc1, Nathalie Luurssen-Masurel, PhD2, Mariska Quirina Nikita Hackert, PhD1, Marc R. Kok, MD PhD1, Tessa M Bosch, PharmD PhD1, Pascal de Jong, MD PhD2, Angelique Weel-Koenders, MSc, PhD, MD3, Deirisa Lopes Barreto, PhD1, Martijn Kuijper, PhD4.
1Maasstad Ziekenhuis, Rotterdam, Netherlands, 2Erasmus MC, Rotterdam, Netherlands, 3Erasmus University & Maasstad Hospital, Rotterdam, Netherlands, 4Maasstad Hospital, Capelle aan den IJssel, Netherlands.
1Maasstad Ziekenhuis, Rotterdam, Netherlands, 2Erasmus MC, Rotterdam, Netherlands, 3Erasmus University & Maasstad Hospital, Rotterdam, Netherlands, 4Maasstad Hospital, Capelle aan den IJssel, Netherlands.
OBJECTIVES: Whereas in the treatment of rheumatoid arthritis (RA) the effects of current pharmacologic treatment on clinical outcomes are well established, less evidence exists on head-to-head comparisons of disease-modifying anti-rheumatic drugs (DMARDs) on patient-reported outcomes (PROs). This systematic review and network meta-analysis (NMA), using both direct- and indirect evidence, aims to evaluate the relative effects of DMARDs on the patient-relevant domains of pain, fatigue, activity limitation, and physical- and emotional health impact.
METHODS: A systematic literature search was conducted using the machine learning tool ASReview. Randomized controlled trials (RCTs) were included that compared cs/b/tsDMARDs with placebo or other cs/b/tsDMARDs, and reported the effects on PROs from the International Consortium of Health Outcomes Measurement (ICHOM) standard set for inflammatory arthritis. Random effects NMA were performed on PRO domains of pain (VAS), fatigue (FACIT-F), activity limitation (HAQ(-DI)) and physical and emotional health impact (SF-36 PCS/MCS).
RESULTS: Overall, DMARDs improved average PRO scores within the domains of pain (VAS: -24.78), fatigue (FACIT-F: -7.24), activity limitation (HAQ-(DI): -0.53), physical health (SF-36 PCS: -6.97) and mental health impact (SF-36 MCS: -4.22). Most DMARDs were significantly better at improving PROs compared to placebo. Methotrexate performed generally worse compared to other DMARDs within all PRO domains. More specifically, rituximab showed strong fatigue improvement versus placebo (FACIT-F: -10.2; 95%CI:-16.1,-4.8). JAK inhibitors were significantly better at improving activity limitation compared to anti-TNF (HAQ-(DI): -0.1; 95%CI:-0.1,-0.2). The effects of DMARDs on mental health appeared to be limited.
CONCLUSIONS: DMARDs improve RA-relevant PROs within the domains of pain, fatigue, activity limitation and physical health, though less on mental health. Large differences favoring one DMARD group over another were not observed, with the exception of rituximab in improving fatigue. Given the relevance of PROs to patients and the absence of clear differences between DMARDs, future research should prioritize including PROs as primary outcomes.
METHODS: A systematic literature search was conducted using the machine learning tool ASReview. Randomized controlled trials (RCTs) were included that compared cs/b/tsDMARDs with placebo or other cs/b/tsDMARDs, and reported the effects on PROs from the International Consortium of Health Outcomes Measurement (ICHOM) standard set for inflammatory arthritis. Random effects NMA were performed on PRO domains of pain (VAS), fatigue (FACIT-F), activity limitation (HAQ(-DI)) and physical and emotional health impact (SF-36 PCS/MCS).
RESULTS: Overall, DMARDs improved average PRO scores within the domains of pain (VAS: -24.78), fatigue (FACIT-F: -7.24), activity limitation (HAQ-(DI): -0.53), physical health (SF-36 PCS: -6.97) and mental health impact (SF-36 MCS: -4.22). Most DMARDs were significantly better at improving PROs compared to placebo. Methotrexate performed generally worse compared to other DMARDs within all PRO domains. More specifically, rituximab showed strong fatigue improvement versus placebo (FACIT-F: -10.2; 95%CI:-16.1,-4.8). JAK inhibitors were significantly better at improving activity limitation compared to anti-TNF (HAQ-(DI): -0.1; 95%CI:-0.1,-0.2). The effects of DMARDs on mental health appeared to be limited.
CONCLUSIONS: DMARDs improve RA-relevant PROs within the domains of pain, fatigue, activity limitation and physical health, though less on mental health. Large differences favoring one DMARD group over another were not observed, with the exception of rituximab in improving fatigue. Given the relevance of PROs to patients and the absence of clear differences between DMARDs, future research should prioritize including PROs as primary outcomes.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
PCR229
Topic
Patient-Centered Research, Study Approaches
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal)