High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study

Abstract Background Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA). However, MTX use is associated with gastrointestinal adverse effects in a number of patients. Early detection of MTX intolerance could help modify the...

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Main Authors: Harjit Singh Nalwa, Tushar Singh Barwal, Parul Chugh, Neha Singh, Neeraj Jain, Lalit Duggal, N. K. Ganguly, Ved Chaturvedi, Shivani Arora Mittal
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Rheumatology
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Online Access:https://doi.org/10.1186/s41927-025-00466-2
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author Harjit Singh Nalwa
Tushar Singh Barwal
Parul Chugh
Neha Singh
Neeraj Jain
Lalit Duggal
N. K. Ganguly
Ved Chaturvedi
Shivani Arora Mittal
author_facet Harjit Singh Nalwa
Tushar Singh Barwal
Parul Chugh
Neha Singh
Neeraj Jain
Lalit Duggal
N. K. Ganguly
Ved Chaturvedi
Shivani Arora Mittal
author_sort Harjit Singh Nalwa
collection DOAJ
description Abstract Background Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA). However, MTX use is associated with gastrointestinal adverse effects in a number of patients. Early detection of MTX intolerance could help modify the treatment strategy, thereby ensuring patient compliance and response. In the present study we aimed to identify the prevalence of MTX intolerance, and associated risk factors in a cohort of Indian RA patients receiving oral MTX therapy. Methods In this cross- sectional study, RA patients who were in regular use of oral or subcutaneous MTX for a minimum duration of three months were included. The participants were evaluated based on their responses to the methotrexate intolerance severity score (MISS) questionnaire. Patients with a MISS score ≥ 6 were considered MTX intolerant. Demographic data encompassing the patient’s age, sex, diet, MTX dosage, duration of use, route of administration, other medication, and disease activity assessed using the DAS-28 CRP was collected using a standardized patient history sheet. Results Out of 200 adult RA patients, 86% were females with an average age of 49.25 ± 11.89 years, and the average duration of MTX use was 46.16 ± 53.40 months. A high prevalence of MTX intolerance (34.5%) was observed in RA patients. Nausea (85.5%) followed by abdominal discomfort (59.42%) were the most prevalent symptoms in intolerant patients. Furthermore, using multivariate analysis, we observed a positive association of MTX intolerance with female gender, disease severity, and MTX dose. Conclusion Although MTX is the one of the most commonly used medication for the treatment of RA, there is significant intolerance to this drug among adult RA patients. The symptoms observed not only occur after MTX intake but are also present before intake (anticipatory) and while thinking of taking MTX (associative). Our data indicates that a MTX dose of 15 mg/week or greater may be associated with intolerance. There is a need to objectively monitor RA patients to identify MTX intolerance early on to ensure mitigation steps for effective treatment response.
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spelling doaj-art-ca295f3e77604f1d84ded119fa6ea5bb2025-08-20T04:02:45ZengBMCBMC Rheumatology2520-10262025-07-01911910.1186/s41927-025-00466-2High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional studyHarjit Singh Nalwa0Tushar Singh Barwal1Parul Chugh2Neha Singh3Neeraj Jain4Lalit Duggal5N. K. Ganguly6Ved Chaturvedi7Shivani Arora Mittal8Department of Biotechnology and Research, Sir Ganga Ram HospitalDepartment of Biotechnology and Research, Sir Ganga Ram HospitalDepartment of Biotechnology and Research, Sir Ganga Ram HospitalDepartment of Biotechnology and Research, Sir Ganga Ram HospitalDepartment of Rheumatology and Clinical Immunology, Sir Ganga Ram HospitalDepartment of Rheumatology and Clinical Immunology, Sir Ganga Ram HospitalDepartment of Biotechnology and Research, Sir Ganga Ram HospitalDepartment of Rheumatology and Clinical Immunology, Sir Ganga Ram HospitalDepartment of Biotechnology and Research, Sir Ganga Ram HospitalAbstract Background Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA). However, MTX use is associated with gastrointestinal adverse effects in a number of patients. Early detection of MTX intolerance could help modify the treatment strategy, thereby ensuring patient compliance and response. In the present study we aimed to identify the prevalence of MTX intolerance, and associated risk factors in a cohort of Indian RA patients receiving oral MTX therapy. Methods In this cross- sectional study, RA patients who were in regular use of oral or subcutaneous MTX for a minimum duration of three months were included. The participants were evaluated based on their responses to the methotrexate intolerance severity score (MISS) questionnaire. Patients with a MISS score ≥ 6 were considered MTX intolerant. Demographic data encompassing the patient’s age, sex, diet, MTX dosage, duration of use, route of administration, other medication, and disease activity assessed using the DAS-28 CRP was collected using a standardized patient history sheet. Results Out of 200 adult RA patients, 86% were females with an average age of 49.25 ± 11.89 years, and the average duration of MTX use was 46.16 ± 53.40 months. A high prevalence of MTX intolerance (34.5%) was observed in RA patients. Nausea (85.5%) followed by abdominal discomfort (59.42%) were the most prevalent symptoms in intolerant patients. Furthermore, using multivariate analysis, we observed a positive association of MTX intolerance with female gender, disease severity, and MTX dose. Conclusion Although MTX is the one of the most commonly used medication for the treatment of RA, there is significant intolerance to this drug among adult RA patients. The symptoms observed not only occur after MTX intake but are also present before intake (anticipatory) and while thinking of taking MTX (associative). Our data indicates that a MTX dose of 15 mg/week or greater may be associated with intolerance. There is a need to objectively monitor RA patients to identify MTX intolerance early on to ensure mitigation steps for effective treatment response.https://doi.org/10.1186/s41927-025-00466-2Rheumatoid arthritisMethotrexateQuestionnaireIntoleranceMethotrexate intolerance severity score (MISS)DAS-28
spellingShingle Harjit Singh Nalwa
Tushar Singh Barwal
Parul Chugh
Neha Singh
Neeraj Jain
Lalit Duggal
N. K. Ganguly
Ved Chaturvedi
Shivani Arora Mittal
High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study
BMC Rheumatology
Rheumatoid arthritis
Methotrexate
Questionnaire
Intolerance
Methotrexate intolerance severity score (MISS)
DAS-28
title High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study
title_full High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study
title_fullStr High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study
title_full_unstemmed High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study
title_short High prevalence of methotrexate intolerance in rheumatoid arthritis patients: a cross-sectional study
title_sort high prevalence of methotrexate intolerance in rheumatoid arthritis patients a cross sectional study
topic Rheumatoid arthritis
Methotrexate
Questionnaire
Intolerance
Methotrexate intolerance severity score (MISS)
DAS-28
url https://doi.org/10.1186/s41927-025-00466-2
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