PREDICTORS OF RESPONSE TO METHOTREXATE MONOTHERAPY IN ACTIVE RHEUMATOID ARTHRITIS: RESULTS FROM A MULTICENTRE, RANDOMIZED CONTROLLED TRIAL (MEIRA)

BackgroundMethotrexate (MTX) is the gold standard, first-line therapy for rheumatoid arthritis (RA). However, not all patients respond to MTX, and the predictors of its response or non-response have not yet been reliably identified. Identification of these predictors will facilitate personalized therapeutic choices, and improve patient outcomes.ObjectivesTo identify the clinico-laboratory predictors of response to MTX monotherapy in active RA.MethodsThis study included patients with active RA (SJC≥2 and TJC≥4) aged 18-55 years, with disease duration <5 years, who were not receiving DMARDs (except HCQ and low-dose prednisolone) and had been enrolled in the multicentre, parallel group RCT comparing two different MTX escalation strategies in RA (MEIRA)1. All these patients received MTX monotherapy which was started at 15 mg/week, escalated to 25 mg/week by 4-8 weeks, and continued till 16 weeks. MTX response was defined as EULAR good or moderate response (based on DAS28-CRP-3v) at 16 weeks. Stepwise, multivariable logistic regression was done using key demographic (age, gender, BMI, comorbidities), clinical (disease duration, DAS28, HAQ), and laboratory parameters (RF, anti-CCP, ESR, CRP, RBC MTX-polyglutamates 1-4, IL-6, MMP-3) as independent variables to identify predictors of MTX response. A two-tailed p-value <0.05 was used for defining statistical significance. (Trial Reg: CTRI/2018/12/016549)ResultsOut of a total of 178 included patients [84% females, mean age 40 (9) years, mean DAS28-CRP=5.4 (1.1)], 113 (63.5%) were classified as MTX responders at 16 weeks. Age (OR=0.95, p=0.01), BMI (OR=1.12, p=0.006), and RF (OR=0.34, p=0.045) were found to be independent predictors of MTX response on multivariable analysis (Table 1). On sensitivity analysis with DAS28-ESR-based EULAR response, age (OR=0.94, p=0.003) and RF (OR=0.42, p=0.059) were replicated as independent predictors of MTX response, in addition to pre-treatment swollen joint count (OR=0.94, p=0.05).Table 1.Results of multivariable logistic regression analysis for prediction of response (as defined by DAS28-CRP-based EULAR good or moderate response) to methotrexate monotherapy in RAVariableOR (unadjusted)Unadjusted p-valueOR (adjusted)Adjusted p-valueAge0.97 (0.93-1.002)0.060.95 (0.91-0.99)0.01Male sex0.78 (0.35-1.76)0.55-BMI1.1 (1.02-1.19)0.011.12 (1.03-1.22)0.006Presence of comorbidities0.67 (0.31-1.44)0.31-Disease duration0.98 (0.79-1.22)0.87-Baseline DAS281.1 (0.81-1.49)0.54-Baseline HAQ1.04 (0.66-1.64)0.86-Baseline TJC1.01 (0.96-1.05)0.72-Baseline SJC0.97 (0.91-1.02)0.24-Baseline ESR1.01 (1.00-1.02)0.27-Baseline CRP1.00 (0.99-1.01)0.85-RF positive0.31 (0.11-0.85)0.020.34 (0.12-0.98)0.045Anti-CCP positive0.73 (0.27-1.99)0.54-MTX PG1 (16 weeks)0.99 (0.94-1.04)0.69-MTX PG2 (16 weeks)0.98 (0.95-1.02)0.37-MTX PG3 (16 weeks)0.99 (0.96-1.02)0.43-MTX PG4 (16 weeks)0.99 (0.95-1.03)0.62-Serum IL-6 (baseline)0.98 (0.95-1.02)0.33-Serum MMP-3 (baseline)1.00 (1.00-1.00)0.48-BMI= Body Mass Index, CCP= Cyclic Citrullinated Peptides, CRP= C-reactive protein, DAS= Disease Activity Score, ESR= Erythrocyte Sedimentation Rate, HAQ= Health Assessment Questionnaire, MTX= Methotrexate, PG= polyglutamate, OR=Odds Ratio, RF=Rheumatoid Factor, SJC= Swollen Joint Count, TJC= Tender Joint CountNote: Only variables with p-value <0.2 on univariable analysis were included in the multivariable analysis.ConclusionYounger age, RF negativity, higher BMI, and lower pre-treatment swollen joint count are potential predictors of response to MTX monotherapy in RA.References[1]Jain S, Dhir V, Aggarwal A, et al. Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial. Ann Rheum Dis. 2021;80(11):1376-1384.Disclosure of InterestsNone declared.