Tags

Type your tag names separated by a space and hit enter

Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis.

Abstract

INTRODUCTION

Methotrexate is the gold-standard DMARD in rheumatoid arthritis but is often associated with "mild" adverse effects like intolerance or laboratory abnormalities. Although non-life threatening, they are responsible for drug discontinuation in 17-50%. There is limited data on clinical and genetic markers that predict their occurrence.

METHODS

This prospective study enrolled patients with active rheumatoid arthritis. They were started on methotrexate at a weekly dose of 15 mg, escalated gradually to reach 25 mg which was continued till the end of the study. Intolerance (symptomatic adverse effects) was ascertained by a questionnaire at 4, 8, 16, and 24 weeks. Laboratory testing for occurrence of cytopenia and/or transaminitis was done at the same study visits. Seven SNPs in four genes involved in methotrexate handling were genotyped using real-time polymerase chain reaction.

RESULTS

This study included 110 patients with rheumatoid arthritis who received methotrexate for 24 weeks; the final mean weekly methotrexate dose was 22.0 ± 4.0 mg. Methotrexate intolerance occurred in 40 (37%), common being nausea (and vomiting) in 29 and anxiety (and dizziness) in 9. It was associated with lower BMI at baseline (21.5 ± 3.7, 23.8 ± 4.6 kg/m2, p = 0.01). FPGS rs10106 was significantly associated with intolerance with an allelic odds ratio (95% CI) of 2.02 (1.14-3.57) and the recessive genetic model (AA+AG versus GG) with an odds ratio of 3.8 (95% CI 1.5-9.6, p = 0.004). A model including both BMI and FPGS rs10106 could modestly predict methotrexate intolerance with an accuracy of 66.3%.

CONCLUSIONS

A clinical-genetic model including BMI and SNP FPGS 10101 was found to have a modest prediction ability for methotrexate intolerance. Key Points • Methotrexate intolerance (symptomatic adverse effects) was common and occurred in 37% patients over 6 months. • SNP FPGS rs10106 and low body mass index were associated with methotrexate intolerance. • Clinico-genetic model had a modest ability of 66% for predicting intolerance.

Authors+Show Affiliations

Department of Internal Medicine (Rheumatology Unit), Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. Department of Biochemistry, Panjab University, Chandigarh, 160014, India.Department of Internal Medicine (Rheumatology Unit), Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. varundhir@gmail.com.Department of Internal Medicine (Rheumatology Unit), Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.Department of Biochemistry, Government Medical College and Hospital Sector 32, Chandigarh, India.Department of Biochemistry, Panjab University, Chandigarh, 160014, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31522319

Citation

Sandhu, Amit, et al. "Clinico-genetic Model to Predict Methotrexate Intolerance in Rheumatoid Arthritis." Clinical Rheumatology, 2019.
Sandhu A, Dhir V, Ahmad S, et al. Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis. Clin Rheumatol. 2019.
Sandhu, A., Dhir, V., Ahmad, S., Dhawan, V., Kaur, J., & Bhatnagar, A. (2019). Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis. Clinical Rheumatology, doi:10.1007/s10067-019-04770-4.
Sandhu A, et al. Clinico-genetic Model to Predict Methotrexate Intolerance in Rheumatoid Arthritis. Clin Rheumatol. 2019 Sep 14; PubMed PMID: 31522319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis. AU - Sandhu,Amit, AU - Dhir,Varun, AU - Ahmad,Shabeer, AU - Dhawan,Veena, AU - Kaur,Jasbinder, AU - Bhatnagar,Archana, Y1 - 2019/09/14/ PY - 2019/05/09/received PY - 2019/09/03/accepted PY - 2019/08/06/revised PY - 2019/9/16/entrez PY - 2019/9/16/pubmed PY - 2019/9/16/medline KW - ABCB1 KW - FPGS KW - Folate KW - Folate antagonist KW - GGH KW - Methotrexate KW - Methotrexate polyglutamate KW - Mutation KW - RFC KW - Rheumatoid arthritis KW - Single nucleotide polymorphism JF - Clinical rheumatology JO - Clin. Rheumatol. N2 - INTRODUCTION: Methotrexate is the gold-standard DMARD in rheumatoid arthritis but is often associated with "mild" adverse effects like intolerance or laboratory abnormalities. Although non-life threatening, they are responsible for drug discontinuation in 17-50%. There is limited data on clinical and genetic markers that predict their occurrence. METHODS: This prospective study enrolled patients with active rheumatoid arthritis. They were started on methotrexate at a weekly dose of 15 mg, escalated gradually to reach 25 mg which was continued till the end of the study. Intolerance (symptomatic adverse effects) was ascertained by a questionnaire at 4, 8, 16, and 24 weeks. Laboratory testing for occurrence of cytopenia and/or transaminitis was done at the same study visits. Seven SNPs in four genes involved in methotrexate handling were genotyped using real-time polymerase chain reaction. RESULTS: This study included 110 patients with rheumatoid arthritis who received methotrexate for 24 weeks; the final mean weekly methotrexate dose was 22.0 ± 4.0 mg. Methotrexate intolerance occurred in 40 (37%), common being nausea (and vomiting) in 29 and anxiety (and dizziness) in 9. It was associated with lower BMI at baseline (21.5 ± 3.7, 23.8 ± 4.6 kg/m2, p = 0.01). FPGS rs10106 was significantly associated with intolerance with an allelic odds ratio (95% CI) of 2.02 (1.14-3.57) and the recessive genetic model (AA+AG versus GG) with an odds ratio of 3.8 (95% CI 1.5-9.6, p = 0.004). A model including both BMI and FPGS rs10106 could modestly predict methotrexate intolerance with an accuracy of 66.3%. CONCLUSIONS: A clinical-genetic model including BMI and SNP FPGS 10101 was found to have a modest prediction ability for methotrexate intolerance. Key Points • Methotrexate intolerance (symptomatic adverse effects) was common and occurred in 37% patients over 6 months. • SNP FPGS rs10106 and low body mass index were associated with methotrexate intolerance. • Clinico-genetic model had a modest ability of 66% for predicting intolerance. SN - 1434-9949 UR - https://www.unboundmedicine.com/medline/citation/31522319/Clinico-genetic_model_to_predict_methotrexate_intolerance_in_rheumatoid_arthritis L2 - https://dx.doi.org/10.1007/s10067-019-04770-4 DB - PRIME DP - Unbound Medicine ER -