Sulfasalazine-Induced Agranulocytosis Is Associated With the Human Leukocyte Antigen Locus

Overview

Journal Clin Pharmacol Ther

Publisher Wiley

Specialty Pharmacology

Date 2017 Aug 2

PMID 28762467

Citations 10

Authors

Mia Wadelius

Niclas Eriksson

Reinhold Kreutz

Emmanuelle Bondon-Guitton

Luisa Ibanez

Alfonso Carvajal

M Isabel Lucena

Esther Sancho Ponce

Mariam Molokhia

Javier Martin

Tomas Axelsson

Hugo Kohnke

Qun-Ying Yue

Patrik K E Magnusson

Mats Bengtsson

Par Hallberg

Affiliations

Soon will be listed here.

Abstract

Agranulocytosis is a serious, although rare, adverse reaction to sulfasalazine, which is used to treat inflammatory joint and bowel disease. We performed a genome-wide association study comprising 9,380,034 polymorphisms and 180 HLA alleles in 36 cases of sulfasalazine-induced agranulocytosis and 5,170 population controls. Sulfasalazine-induced agranulocytosis was significantly associated with the HLA region on chromosome 6. The top hit (rs9266634) was located close to HLA-B, odds ratio (OR) 5.36 (95% confidence interval (CI) (2.97, 9.69) P = 2.55 × 10 ). We HLA-sequenced a second cohort consisting of 40 cases and 142 treated controls, and confirmed significant associations with HLA-B*08:01, OR = 2.25 (95% CI (1.02, 4.97) P = 0.0439), in particular the HLA-B*08:01 haplotype HLA-DQB1*02:01-DRB1*03:01-B*08:01-C*07:01, OR = 3.79 (95% CI (1.63, 8.80) P = 0.0019), and with HLA-A*31:01, OR = 4.81 (95% CI (1.52, 15.26) P = 0.0077). The number needed to test for HLA-B*08:01 and HLA-A*31:01 to avoid one case was estimated to be 1,500. We suggest that intensified monitoring or alternative treatment should be considered for known carriers of HLA-B*08:01 or HLA-A*31:01.

Citing Articles

Sulfasalazine-Induced Agranulocytosis: A Case Series and Review of Literature.

Chettri N, Mamadapur M, Subramanian R, Sandhya D, Kumar B R J Mediterr J Rheumatol. 2024; 35(3):479-483.

PMID: 39463872 PMC: 11500113. DOI: 10.31138/mjr.010124.sia.

Safety assessment of sulfasalazine: a pharmacovigilance study based on FAERS database.

Ye W, Ding Y, Li M, Tian Z, Wang S, Liu Z Front Pharmacol. 2024; 15:1452300.

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Sulfasalazine-Induced Delayed Hypersensitivity Reaction Presenting as Fever, Aseptic Meningitis, and Mesenteric Panniculitis in a Patient with Seronegative Arthritis.

Ng T, Davel S, OConnor K Am J Case Rep. 2023; 24:e941623.

PMID: 37924204 PMC: 10630587. DOI: 10.12659/AJCR.941623.

Genomewide Association Studies in Pharmacogenomics.

McInnes G, Yee S, Pershad Y, Altman R Clin Pharmacol Ther. 2021; 110(3):637-648.

PMID: 34185318 PMC: 8376796. DOI: 10.1002/cpt.2349.

Genome wide study of tardive dyskinesia in schizophrenia.

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