Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 21, 2012; 18(47): 6967-6973
Published online Dec 21, 2012. doi: 10.3748/wjg.v18.i47.6967
Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease
Zuzana Zelinkova, Evelien Bultman, Lauran Vogelaar, Cheima Bouziane, Ernst J Kuipers, C Janneke van der Woude
Zuzana Zelinkova, Evelien Bultman, Lauran Vogelaar, Cheima Bouziane, Ernst J Kuipers, C Janneke van der Woude, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, NL-3000 CA Rotterdam, The Netherlands
Author contributions: Zelinkova Z and van der Woude CJ designed research; Zelinkova Z, Bultman E, Vogelaar L, Bouziane C collected data; Zelinkova Z analysed data; Zelinkova Z wrote the paper; Kuipers EJ and van der Woude CJ provided the critical review of the manuscript.
Correspondence to: Zuzana Zelinkova, MD, PhD, Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, PO Box 2040, NL-3000 CA Rotterdam, The Netherlands. z.zelinkova@erasmusmc.nl
Telephone: +31-10-7040704 Fax: +31-10-7032793
Received: May 10, 2012
Revised: August 14, 2012
Accepted: August 16, 2012
Published online: December 21, 2012
Abstract

AIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients.

METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system. The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD, i.e., thiopurines, methotrexate, cyclosporine, tacrolimus and anti-tumor necrosis factor agents (anti-TNF); infliximab (IFX), adalimumab (ADA) and/or certolizumab, were further analyzed. The reported ADR to immune suppressive drugs were noted. The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication. Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further follow-up at the outpatient clinic were excluded. The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ2 test.

RESULTS: In total, 1009 IBD patients were identified in the electronic diagnosis registration system. Out of these 1009 patients, 843 patients were eligible for further analysis. There were 386 males (46%), mean age 42 years (range: 16-87 years) with a mean duration of the disease of 14 years (range: 0-54 years); 578 patients with Crohn’s disease, 244 with ulcerative colitis and 21 with unclassified colitis. Seventy percent (586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course, the majority of the patients (546 pts, 65%) used thiopurines, 176 pts (21%) methotrexate, 46 pts (5%) cyclosporine and one patient tacrolimus. One third (240 pts, 28%) of patients were treated with anti-TNF, the majority of patients (227 pts, 27%) used IFX, 99 (12%) used ADA and five patients certolizumab. There were no differences between male and female patients in the use of immune suppressive agents. With regards to ADR, no differences between males and females were observed in the incidence of ADR to thiopurines, methotrexate and cyclosporine. Among 77 pts who developed ADR to one or more anti-TNF agents, significantly more females (54 pts, 39% of all anti-TNF treated women) than males (23 pts, 23% of all anti-TNF treated men) experienced ADR to an anti-TNF agent [P = 0.011; odds ratio (OR) 2.2, 95%CI 1.2-3.8]. The most frequent ADR to both anti-TNF agents, IFX and ADA, were allergic reactions (15% of all IFX users and 7% of all patients treated with ADA) and for both agents a significantly higher rate of allergic reactions in females compared with males was observed. As a result of ADR, 36 patients (15% of all patients using anti-TNF) stopped the treatment, with significantly higher stopping rate among females (27 females, 19% vs 9 males, 9%, P = 0.024).

CONCLUSION: Treatment with anti-TNF antibodies is accompanied by sexual dimorphic profile of ADR with female patients being more at risk for allergic reactions and subsequent discontinuation of the treatment.

Keywords: Adverse drug reactions; Sexual dimorphism; Infliximab; Adalimumab; Inflammatory bowel disease