Dataset Information

Association of SLCO1B1 *14 Allele with Poor Response to Methotrexate in Juvenile Idiopathic Arthritis Patients.

ABSTRACT: Objective:Variants in the SLCO1B1 gene, encoding a hepatic methotrexate (MTX) transporter, affect clearance of high-dose MTX. We tested whether in the *14 and *15 alleles of SLCO1B1 influenced the response to low-dose MTX in juvenile idiopathic arthritis (JIA) patients. Methods:The study included 310 JIA patients genotyped for three single nucleotide polymorphisms (SNPs) in SLCO1B1 (rs4149056, rs2306283, and rs11045819). A patient's SLCO1B1 diplotype was determined by combining the SNPs into the *1a, *1b, *4, *5, *14, and *15 alleles. Number of active joints at follow-up (visit closest to 6 months of treatment and prior to starting a tumor necrosis factor inhibitor) was used as the dependent variable in a negative binomial regression model that included active joint count at baseline as a covariate. Results:The SLCO1B1*14 allele was associated with less response to MTX (P = 0.024) and the *15 allele was not associated with response to MTX (P = 0.392). Conclusion:SLCO1B1 alleles may be associated with poor response to MTX in JIA patients. The *14 allele has been associated with fast clearance (low exposure) after high-dose MTX in patients with leukemia. Thus, the SLCO1B1 gene may be informative for precision dosing of MTX in JIA patients. Patients carrying the *14 allele may require a higher dose than noncarriers to achieve a similar response to MTX.

SUBMITTER: Ramsey LB

PROVIDER: S-EPMC6858017 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Association of <i>SLCO1B1</i> *14 Allele with Poor Response to Methotrexate in Juvenile Idiopathic Arthritis Patients.

Ramsey Laura B LB Moncrieffe Halima H Smith Chelsey N CN Sudman Marc M Marion Miranda C MC Langefeld Carl D CD Becker Mara L ML Thompson Susan D SD

ACR open rheumatology 20190315 1

<h4>Objective</h4>Variants in the <i>SLCO1B1</i> gene, encoding a hepatic methotrexate (MTX) transporter, affect clearance of high-dose MTX. We tested whether in the *14 and *15 alleles of <i>SLCO1B1</i> influenced the response to low-dose MTX in juvenile idiopathic arthritis (JIA) patients.<h4>Methods</h4>The study included 310 JIA patients genotyped for three single nucleotide polymorphisms (SNPs) in <i>SLCO1B1</i> (rs4149056, rs2306283, and rs11045819). A patient's <i>SLCO1B1</i> diplotype wa ...[more]

PMID: 31777781

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Project description:The objective of this study was to determine the effectiveness of MRP8/14 as a predictor of disease flare in patients with juvenile idiopathic arthritis (JIA) following the withdrawal of methotrexate (MTX) in a routine clinical setting. All MRP8/14 tests performed at a single centre in a 27-month period were considered for analysis. Patients were assessed against criteria for inactive disease and subsequent disease flare. Decisions on whether or not to stop treatment were recorded. MRP8/14 results were assessed in conjunction with clinical information. Clinicians were also surveyed to investigate if MRP8/14 influenced their decision to discontinue MTX where this was available at that time point. One hundred four cases met the inclusion criteria during the study period. Although there was no significant difference in flares between patients with an elevated or low MRP8/14 value, in those who stopped MTX (n = 22), no patients with a low MRP8/14 (≤ 4000 ng/ml) result flared (follow-up time 12 months). Clinicians reported that for patients with clinically inactive disease and an elevated MRP8/14 result (> 4000 ng/ml), none would advise withdrawal of MTX. Low MRP8/14 was interpreted favourably when considering stopping MTX treatment in patients with JIA. Implementation of MRP8/14 testing has changed clinical practice at this centre. However, the observation that some patients in our cohort who had an elevated MRP8/14 value did not flare after stopping MTX for non-disease-related reasons highlights the need for further biomarkers to predict the risk of flare off medication in JIA and aid clinicians in treatment decisions. Key Points • First study of serum MRP8/14 measurement in clinical practice to inform treatment decisions in patients with JIA. • No patients with a low MRP8/14 test result went on to suffer a disease flare in 12 months of follow follow-up. • Further biomarkers are needed to predict the risk of flare off medication in JIA and treatment decisions.

Dataset Information

Association of SLCO1B1 *14 Allele with Poor Response to Methotrexate in Juvenile Idiopathic Arthritis Patients.

Publications

Association of <i>SLCO1B1</i> *14 Allele with Poor Response to Methotrexate in Juvenile Idiopathic Arthritis Patients.

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