Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis

Sandhu, Amit; Dhir, Varun; Ahmad, Shabeer; Dhawan, Veena; Kaur, Jasbinder; Bhatnagar, Archana

doi:10.1007/s10067-019-04770-4

Cited by 8 publications

(12 citation statements)

References 21 publications

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“…All variables with P <0. 15 were entered into a model using multivariable logistic regression. All tests were done on IBM SPSS Statistics, Version 25.0 (IBM Corp, Armonk, NY, USA).…”

Section: Discussionmentioning

confidence: 99%

“…Two rheumatologists (VD, SN), a fellow (SidJ) and a medicine resident (DV) reviewed previous studies 4‐6,12,13 and our own symptom lists used in prior studies with MTX 14‐16 . Fourteen unpleasant symptoms were included in a preliminary questionnaire for MTX intolerance (Supplementary Figure ).…”

Section: Methodsmentioning

confidence: 99%

“…Two rheumatologists (VD, SN), a fellow (SidJ) and a medicine resident (DV) reviewed previous studies [4][5][6]12,13 and our own symptom lists used in prior studies with MTX. [14][15][16] Fourteen unpleasant symptoms were included in a preliminary questionnaire for MTX intolerance (Supplementary Figure S1). The first 8 questions needed to be answered as either no (scored as 0) or yes (rated as mild, moderate or severe; scored as 1, 2, 3) and patients needed to mention how long the symptom lasted per week (in days from 0.5 to 7).…”

Section: Development Of a Preliminary Questionnairementioning

confidence: 99%

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Assessing methotrexate intolerance and its prevalence in rheumatoid arthritis: Development and validation of the MISA questionnaire

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Objective: Methotrexate (MTX) intolerance refers to unpleasant symptoms that accompany use of MTX. Although a validated questionnaire on MTX intolerance exists for children with juvenile idiopathic arthritis, it is lacking for adult rheumatoid arthritis (RA) patients.Methods: A 10-item questionnaire called Methotrexate Intolerance and Severity assessment in Adults (MISA) was developed to assess MTX intolerance. On receiver operating characteristic analysis, its predictive ability was compared to Methotrexate Intolerance Severity Score (MISS), a validated questionnaire for children. Subsequently, prevalence and associations of intolerance were assessed in 414 RA patients. After 1 year, discontinuation of MTX was compared between patients with and without MTX intolerance.Results: MISA score had a good predictive ability (area under the curve [AUC] of 0.904), with sensitivity and specificity of 91.4% and 84.3% (cut-off ≥1) to correctly classify MTX intolerance and was better than MISS score (AUC of 0.823). Among 414 RA patients, 159 (38.4%) had MTX intolerance, with common symptoms being nausea, lethargy, irritability and loss of appetite. On multivariable analysis, age (odds ratio 0.972) and body mass index (odds ratio 1.061) were significant predictors of MTX intolerance. At 1 year, a higher proportion of patients with intolerance than without intolerance had discontinued MTX (odds ratio 2.4, P = 0.02). To classify severity of intolerance, another score, MISA-cross-product, was developed and validated, with an AUC of 0.899. Conclusions:The newly developed MISA questionnaire and score had good predictive ability to diagnose MTX intolerance. Intolerance to MTX was common, being found in one-third of RA patients.

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“…All variables with P <0. 15 were entered into a model using multivariable logistic regression. All tests were done on IBM SPSS Statistics, Version 25.0 (IBM Corp, Armonk, NY, USA).…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Development Of a Preliminary Questionnairementioning

confidence: 99%

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Assessing methotrexate intolerance and its prevalence in rheumatoid arthritis: Development and validation of the MISA questionnaire

et al. 2021

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“…In contrast, the relationship between MTX therapy and pulmonary response to ABA is challenging to explain [ 40 ]. MTX-induced pulmonary toxicity, presented as acute/subacute or rarely as chronic pneumonia, has been a subject of debate for many years [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Abatacept in rheumatoid arthritis-associated interstitial lung disease: short-term outcomes and predictors of progression

et al. 2021

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Introduction Interstitial lung disease in rheumatoid arthritis (RA-ILD) is an extra-articular involvement that impairs the prognosis and for which there is still no well-coded treatment. The aim of this study was to evaluate abatacept (ABA) effectiveness and safety in patients with RA-ILD. Methods RA-ILD patients who started ABA treatment were consecutively enrolled. Chest high-resolution computed tomography (HRCT), clinical, laboratory and respiratory function variables were collected at baseline and after 18 months of ABA treatment. HRCT abnormalities were evaluated using a computer-aided method (CaM). ABA response was established based on the change in the percentage of fibrosis evaluated at HRCT-CaM, dividing patients into “worsened” (progression ≥ 15%), “improved” (reduction ≥ 15%), and “stable” (changes within the 15% range). The multivariate regression model was used to assess the associations between RA characteristics and ABA response. Results Forty-four patients (81% women, mean age 59.1 ± 8.0, mean disease duration of 7.5 ± 3.1 years) were studied. Five patients (11.4%) showed RA-ILD progression, 32 patients (72.6%) were considered stable, and 7 patients (16.0%) showed an RA-ILD improvement. The proportion of current smokers was significantly different between “worsened” patients, respect to those defined as "improved/stable” (p = 0.01). Current smoking habit (p = 0.005) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in multivariate regression analysis. Conclusion Treatment with ABA is associated with a RA-ILD stability or improvement in the 88.6% of patients. Current smoking habit and concomitant treatment with methotrexate are the modifiable factors associated with RA-ILD worsening. Key Points• Abatacept plays a favourable role in the control of RA-ILD, with a significant worsening in only 11.4% of patients during a 18-month follow-up period.• The predictive variables related to RA-ILD progression during abatacept therapy are the concomitant treatment with methotrexate and current smoking habit.

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“…We reviewed the single nucleotide polymorphism (SNPs) of these MTX metabolizing pathway genes with a allele frequency of at least 10% and found significant association of adverse events with SNPs, FPGS rs10106 [p = 0.01, OR 2.11, 95% CI (1.20-3.71)] and FPGS rs1544105 [p = 0.02, OR 1.93, 95% CI (1.15-3.35)] [9]. We also developed a model that predicted methotrexate intolerance with an accuracy of 66.3% and used both BMI and FPGS rs10106 as independent (predictor) variables [10]. Moya et al also reported the association of this SNP with MTX toxicity in RA patients [11].…”

Section: Pharmacogenomics and Adverse Eventsmentioning

confidence: 99%

Are long-chain methotrexate polyglutamate levels the reason for LD-MTX related adverse events in inflammatory arthritis?

Sandhu

Kaur

Dhir

et al. 2021

Expert Review of Clinical Pharmacology

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Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis

Cited by 8 publications

References 21 publications

Assessing methotrexate intolerance and its prevalence in rheumatoid arthritis: Development and validation of the MISA questionnaire

Assessing methotrexate intolerance and its prevalence in rheumatoid arthritis: Development and validation of the MISA questionnaire

Abatacept in rheumatoid arthritis-associated interstitial lung disease: short-term outcomes and predictors of progression

Are long-chain methotrexate polyglutamate levels the reason for LD-MTX related adverse events in inflammatory arthritis?

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