POS0667 CHARACTERIZING NON-RESPONSE TO METHOTREXATE MONOTHERAPY AMONG RHEUMATOID ARTHRITIS PATIENTS IN A LARGE REAL-WORLD LONGITUDINAL COHORT

Abstract

BackgroundMethotrexate (MTX) monotherapy is the first choice among disease-modifying drugs (DMARDs) for most moderate-to-severe rheumatoid arthritis (RA) patients, consistent with treatment guidelines.1 However, response to, and tolerability of, MTX varies among patients.2 Understanding the proportion of patients with MTX non-response in a real-world setting and identifying its predictors could enable earlier access to alternative or additional medications and improve management of disease progression.ObjectivesThe objectives of this study were, using data from a large, geographically representative US cohort of RA patients, to describe the pattern of non-response among patients initiating MTX monotherapy and to identify predictors of non-response to MTX.MethodsThe OM1 RA Registry (OM1, Inc; Boston, MA) follows more than 210,000 RA patients in the US managed by rheumatologists longitudinally with deep clinical data, including laboratory, patient-reported and disease activity information, and linked administrative claims starting from 2013. In this retrospective observational study, patients aged ≥ 18 years initiating MTX between 01 January 2014 and 01 August 2020 without previous bDMARD/tsDMARD utilization were identified. The first MTX date was the index date, with ≥1 Clinical Disease Activity Index (CDAI) measurement and ≥2 all-cause healthcare encounters required in the preceding 12 months (baseline). Patients initiating a bDMARD/tsDMARD within 30 days of the index date or with a history of other conditions where the same bDMARD/tsDMARDs are indicated were excluded. MTX non-response was defined as failing to attain remission or low disease activity (i.e., CDAI >10) within 4 to 8 months and/or the initiation of a bDMARD/tsDMARD within 8 months following the index date (with or without continuing MTX; non-response could include patients discontinuing MTX due to tolerability). Baseline characteristics were summarized with descriptive statistics. Multivariate logistic regression with age, gender, region, race, payor, year of index, the most recent CDAI and body mass index (BMI) measurements from the baseline, and Charlson comorbidity index (CCI) was used to investigate risk factors of non-response. P value was considered significant if <0.01.ResultsAmong 6,648 eligible RA patients, 3,748 (56.4%) were classified as non-responders. Baseline charactesistics are summarized in Table 1. Being female (OR=1.3), increasing baseline CDAI (OR: Low activity=1.9, moderate activity=8.1, high activity=13.0) and higher BMI (OR=1.01) were significantly associated with non-response. Being older was found protective of non-response (OR=0.98). The C-statistic was 0.74.Table 1.Baseline Characteristics Overall and by Response StatusStatisticOverallRespondersNon-respondersAge61.6 (13.3)63.9 (13.0)59.8 (13.3)Female5,059 (76.1%)2,096 (72.3%)2,963 (79.1%)Region MIDWEST905 (13.6%)366 (12.6%)539 (14.4%) NORTHEAST1,115 (16.7%)520 (17.9%)595 (15.9%) SOUTH4,063 (61.1%)1,759 (60.7%)2,304 (61.5%) WEST565 (8.5%)255 (8.8%)310 (8.3%)Race BLACK597 (9.0%)243 (8.4%)354 (9.5%) WHITE4,305 (64.8%)1,935 (66.7%)2,370 (63.2%) OTHER166 (2.5%)73 (2.5%)93 (2.5%) UNKNOWN1,580 (23.8%)649 (22.4%)931 (24.8%)Payor COMMERCIAL3,768 (56.7%)1,516 (52.3%)2,252 (60.1%) MEDICARE2,590 (39.0%)1,273 (43.9%)1,317 (35.1%) MEDICAID290 (4.4%)111 (3.8%)179 (4.8%)CDAI15.6 (10.4)11.3 (9.5)18.9 (9.8)CCI1.4 (1.1)1.4 (1.1)1.4 (1.1)BMI30.4 (7.1)29.7 (6.8)30.9 (7.3)ConclusionWe found that over half of patients qualified as MTX non-responders at approximately 6 months. Significant predictors of non-response were younger age, female gender, higher CDAI score and BMI. Maximizing improvement as quickly as possible and deploying more tailored escalation of care may be aided by identifying RA patients at higher risk of early MTX treatment failure.References[1]Smolen JS, et al. Annals of the Rheumatic Diseases 2020;79:685-699.[2]Verstappen SM, et al. Int J Clin Rheumtol. 2012;7(5):559–567.Disclosure of InterestsZeynep Icten: None declared, Kathryn Starzyk: None declared, Mark Friedman: None declared, Joseph Menzin Grant/research support from: Grant support