Background/Purpose: Methotrexate (MTX), a synthetic disease-modifying antirheumatic drug (DMARD), is the most commonly used medication for rheumatoid arthritis (RA). Considerable variations between patients taking MTX exist due to its potential adverse effects and tolerability issues. Although patient reported outcomes have been used for evaluating effectiveness of RA treatments in clinical trials, much less is understood from real-world settings. This study evaluated the association between MTX use and fatigue in the PCORI-funded Patient Powered Research Network for adult rheumatologic conditions, ArthritisPower.

Methods: Patients in the ArthritisPower registry were invited to provide medication information and PROs including the RAPID3 and 4 PROMIS instruments (pain interference, physical function, fatigue, and sleep disturbance) plus disease-specific information via a mobile application (App) on their smartphone or computer. Patients who used selected RA medications of interest (glucocorticoids, non-biologic DMARDs, biologics) and answered ≥ 1 instrument were eligible this study. We calculated the mean and standard deviation (SD) of RAPID3 and the 4 PROs across different RA treatments cross-sectionally. Multivariable regression analysis with repeated measures was used to evaluate the association between MTX use and fatigue.

Results: As of June 2017, ArthritisPower had recruited 5,830 patients; approximately 57% had RA. A total of 469 participants had RA medication use and answered relevant PROMIS instruments, with mean (SD) age of 48.3 (11.5) years; 32.0% used glucocorticoids, 83.2% used non biologic DMARDs, and 62.5% used biologics. The mean score for pain interference was 62.7 (SD: 7.3), physical function 38.0 (6.9), sleep disturbance 56.9 (8.4), fatigue 62.3 (8.5), and RAPID3 14.7 (5.7). Among different RA treatments, patients on biologic monotherapy had the highest scores for pain interference, sleep disturbance, fatigue, and RAPID3, whereas MTX monotherapy had the lowest. In contrast, MTX monotherapy had the highest physical function score whereas biologic monotherapy had the lowest (Table). Using fatigue as an example, MTX use is associated with 2.29 (95% confidence interval: -3.2, -1.4) units of lower fatigue score after adjusting for age, gender, race, insurance, employment and concurrent RA medications and medical conditions.

Conclusion: PROMIS measures are feasible to capture from patients with Smartphone and Web Apps. Despite potential concerns related to fatigue associated with use of MTX, these results suggest that on average, MTX is associated with lower fatigue scores. RA patients on MTX might be associated with better PROs, especially when it was combined with biologics use. More longitudinal data analyses are needed to better understand the relationship.