Background:Methotrexate (MTX) is frequently used in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) because of its beneficial effects in both populations1-3. Despite the well-known benefits of MTX, it is associated with a number of potential side effects4-6These include nausea and fatigue, are often temporally related to the timing of weekly MTX administration, and can be severe. The combined patient-reported side effects, along with potential of long-term toxicity, may make use of MTX more burdensome. Currently, there is a gap in patient-centered studies that focus on patients’ experience with MTX.Objectives:Examine patient temporal experience of fatigue and nausea relating to oral MTX therapy for the treatment of RA and PsA.Methods:Adult US patients in the ArthritisPower registry with self-reported RA or PsA taking MTX for less than 10 years were invited to participate in the study via email invitation. Participants (pts) completed a screener and brief online survey. In an ancillary study to the ArthritisPower registry and using a self-controlled case series study design where pts serve as their own control to avoid between-person confounding, pts were asked to complete a set of up to 8 assessments within 6-36 hours (‘risk’) and 96-144 hours (‘control’) after taking their oral dose of MTX each week, for up to 4 weeks. Risk and control windows were selected based on the expected temporal relationship between MTX use and peak onset of these symptoms. Assessments included PROMIS short forms for same-day Fatigue, same-day Nausea/Vomiting, and Patient Global. Descriptive statistics were conducted using paired t-tests two-way comparisons. Within-person change in PROMIS scores between the risk (1-2 days after MTX) and control (4-6 days after MTX) windows were analyzed using mixed models for repeated measures, stratified on whether pts reported fatigue or nausea with MTX at baseline. Recruitment for this study is ongoing.Results:As of December 2019, 91 pts had participated, of whom 76.9% were living with RA and 28.6% with PsA, with mean baseline PROMIS Patient Global score (SD) of 39.5 (7.1). Mean age (SD) was 50.9 (12.0) years, 84.6% female, 92.3% White, with mean BMI 33.7 (8.8). Mean duration of MTX treatment among current users was 2.1 (2.8) years. Among pts, 41.8% were on a biologic DMARD and 58.2% on non-biologic DMARDs only. Among pts reporting baseline nausea (n=30, 33.0%) where paired within-week measures were observed (n=64 observations among 20 pts), the mean increase in the PROMIS Nausea score was 4.5 units (adjusted p=0.003). Among those reporting MTX-associated fatigue (n=39, 42.9%) as a side effect of MTX on their baseline survey where paired within-week measures were observed (n=96 observations among 28 pts), the mean increase in PROMIS Fatigue was 4.7 (adjusted p=0.004) units. In those pts, the proportion of pts with worsened nausea and fatigue with minimally important difference of >5 units7-8was 40.0% (nausea), and 60.7% (fatigue) [Figures 1 and 2].Conclusion:People taking MTX to manage RA or PsA commonly experience bothersome side effects, notably fatigue and nausea, that are temporally related to weekly MTX dosing. In this sample, one-third or more of pts were bothered by nausea or fatigue shortly after MTX dosing, many of them with clinically meaningful symptoms.References:[1]Singh JA, et al.Arthritis Rheumatol. 2016;68:1-26.[2]Singh JA, et al.Arthritis Rheumatol. 2019;71:5-32.[3]Mease P.Bull NYU Hosp Jt Dis. 2013;71.(suppl 1):S41.[4]Wang W, et al.Eur J Med Chem. 2018;158:502-516.[5]Wilsdon TD, et al.Cochrane Database Syst Rev. 2019;1:CD012722.[6]Husted JA, et al.Ann Rheum Dis. 2009;68:1553-1558.[7]Norman GR, et al.Med Care. 2003;41:582-92.[8]Bingham CO, et al.J Patient Rep Outcomes. 2019;3:14.Disclosure of Interests:W. Benjamin Nowell: None declared, Elaine Karis Shareholder of: Amgen Inc., Employee of: Amgen Inc., Kelly Gavigan: None declared, Laura Stradford: None declared, Scott Stryker Shareholder of: Amgen Inc., Employee of: Amgen Inc., Huifeng Yun Grant/research support from: Bristol-Myers Squibb and Pfizer, Shilpa Venkatachalam: None declared, Greg Kricorian Shareholder of: Amgen Inc., Employee of: Amgen Inc., Lang Chen: None declared, Hong Zhao: None declared, Fenglong Xie: None declared, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB
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