POS0679 A NEW QUESTIONNAIRE AND SCORE (MISA) FOR ASSESSING METHOTREXATE INTOLERANCE IN RHEUMATOID ARTHRITIS
Authors: V. Dhir, D. V, S. Jain, V. Pai, A. Sharma, S. K. Sharma, G. Naidu, S. Jain
Journal: Annals of the Rheumatic Diseases (2021)

Background: Methotrexate (MTX) intolerance refers to unpleasant symptoms that accompany use of MTX and may lead to its discontinuation. However, it lacks a validated score in RA patients; with the only option being to use the MISS score which was validated for use in children and not adults. Objectives: To develop and validate a questionnaire and score (s) for measuring MTX intolerance and its severity in rheumatoid arthritis. Methods: A 10-item questionnaire called ‘Methotrexate Intolerance and Severity assessment in Adults’ (MISA) was validated in 105 RA patients. A score was calculated by adding the scores of first 7 questions (0 to 3 based on severity on symptoms), to last 3 questions (0 or 1); it ranged from 0 to 24 (MISA score) and was assessed for correctly classifying MTX intolerance (compared to an interview) by ROC analysis. Its area-under-curve (AUC) was compared with ‘Methotrexate Intolerance Severity Score’ (MISS), developed for children. Subsequently, it was administered to 414 RA patients to assess the prevalence and associations of MTX intolerance. In addition, the MISA cross-products score, that was calculated by adding the cross-products (severity (1 to 3) x duration per week (0.5 to 7 days)) of symptoms, was compared to MISA and MISS for assessing severity of intolerance. Results: In the initial phase, 105 RA patients on MTX≥6 months were included, a majority were female (87%), mean age was 51 (13.4) years and methotrexate dose was 18.8±6 mg/week. Thirty-five (33%) were found to be intolerant to MTX based on interview. MISA score had a good predictive ability (AUC of 0.904), to correctly classify MTX intolerance, and was better than MISS score (AUC of 0.823) (Figure 1A). The optimal cut-off for MISA was ≥1, with a sensitivity and specificity of 91.4% and 84.3%. Using the MISA score (≥1), 38.4% of 414 RA patients were found to have MTX intolerance: with nausea, lethargy and irritability being common symptoms. (Figure 1B, C) On multivariable analysis, age (OR 0.972) and BMI (OR 1.061) were significant predictors of MTX intolerance. (Table 1) On assessing for severity of intolerance, MISA cross product score performed the best, with an area-under-curve of 0.899 (95% CI 0.831-0.966), being higher than AUC for MISS and MISA score which were 0.847 (95% CI 0.768-0.927) and 0.837 (95% CI 0.754-0.920). Conclusion: MISA is the first validated questionnaire for assessing methotrexate intolerance in rheumatoid arthritis, with the MISA score having a good accuracy (at cut-off ≥1), to detect MTX intolerance. Methotrexate intolerance was present in more than one-third of RA patients, with nausea, lethargy and irritability being most common. Table 1. Baseline characteristics of 414 RA patients. Variable All (n=414) Tolerant (n=255) Intolerant (n=159) p-value tol. vs ntol. P-value multivariable model Females, n (%) 370 (89) 231 (91) 139 (87) 0.31 Age, yrs, mean (SD) 50 (12.5) 51.2 (12.6) 48.2 (12.2) 0.016* 0.008** Duration of RA, yrs, mean (SD) 10.0 (7.0) 10.8 (7.4) 9.6 (6.3) 0.168 BMI, Kg/m 2a , mean (SD) 24.0 (4.9) 23.6 (4.9) 24.6 (4.7) 0.107 0.03* RF positive b , n (%) 300 (73) 191 (82) 109 (78) 0.29 CDAI, mean (±SD) 14.0 (11.8) 14 (12.1) 14.1 (11.4) 0.69 Dose of MTX, mg/wk, mean (SD) 18.6 (5.6) 18.6 (5.5) 18.7 (5.8) 0.83 Injectable MTX, n (%) 47 (11) 25 (10) 22 (14) 0.21 Use of FA, n (%) 395 (95) 241 (95) 154 (97) 0.27 Use of other DMARD, n (%) 272 (66) 160 (62) 112 (70) 0.11 HCQ n (%) 209 (51) 123 (48) 86 (54) 0.25 Prednisolone n (%) 156 (38) 87 (34) 69 (43) 0.058 0.21 Using antiemetics, n (%) 12 (3) 1 (0.5) 11 (7) &lt;0.001 a Available for 262 patients b Available for 372 patients Figure 1. Figure showing the ROC curve for MISA and MISS questionnaires for MTX intolerance (A), Bar diagram showing the prevalence of various symptoms of intolerance in 414 RA patients (B), and Box-and-whiskers plot showing the duration of unpleasant symptoms (C). Disclosure of Interests: None declared