Brief Article
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World J Gastroenterol. Jul 21, 2013; 19(27): 4344-4350
Published online Jul 21, 2013. doi: 10.3748/wjg.v19.i27.4344
Low rates of adherence for tumor necrosis factor-α inhibitors in Crohn’s disease and rheumatoid arthritis: Results of a systematic review
Herma H Fidder, Maartje MJ Singendonk, Mike van der Have, Bas Oldenburg, Martijn GH van Oijen
Herma H Fidder, Maartje MJ Singendonk, Mike van der Have, Bas Oldenburg, Martijn GH van Oijen, Department of Gastroenterology and Hepatology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Author contributions: Fidder HH, Singendonk MMJ and van Oijen MGH contributed equally to this work and designed and performed the research and wrote the paper, van der Have M and Oldenburg B contributed to the writing process.
Correspondence to: Herma H Fidder, MD, PhD, Department of Gastroenterology and Hepatology, University Medical Center Utrecht, PO Box 85500 (internal code F02.618), 3508 GA Utrecht, The Netherlands. h.fidder@umcutrecht.nl
Telephone: +31-88-7557325  Fax: +31-88-7555533
Received: December 24, 2012
Revised: February 12, 2013
Accepted: March 21, 2013
Published online: July 21, 2013
Processing time: 208 Days and 22.1 Hours
Abstract

AIM: To investigate adherence rates in tumor necrosis factor-α (TNF-α)-inhibitors in Crohn’s disease (CD) and rheumatoid arthritis (RA) by systematic review of medical literature.

METHODS: A structured search of PubMed between 2001 and 2011 was conducted to identify publications that assessed treatment with TNF-α inhibitors providing data about adherence in CD and RA. Therapeutic agents of interest where adalimumab, infliximab and etanercept, since these are most commonly used for both diseases. Studies assessing only drug survival or continuation rates were excluded. Data describing adherence with TNF-α inhibitors were extracted for each selected study. Given the large variation between definitions of measurement of adherence, the definitions as used by the authors where used in our calculations. Data were tabulated and also presented descriptively. Sample size-weighted pooled proportions of patients adherent to therapy and their 95%CI were calculated. To compare adherence between infliximab, adalimumab and etanercept, the adherence rates where graphed alongside two axes. Possible determinants of adherence were extracted from the selected studies and tabulated using the presented OR.

RESULTS: Three studies on CD and three on RA were identified, involving a total of 8147 patients (953 CD and 7194 RA). We identified considerable variation in the definitions and methodologies of measuring adherence between studies. The calculated overall sample size-weighted pooled proportion for adherence to TNF-α inhibitors in CD was 70% (95%CI: 67%-73%) and 59% in RA (95%CI: 58%-60%). In CD the adherence rate for infliximab (72%) was highercompared to adalimumab (55%), with a relative risk of 1.61 (95%CI: 1.27-2.03), whereas in RA adherence for adalimumab (67%) was higher compared to both infliximab (48%) and etanercept (59%), with a relative risk of 1.41 (95%CI: 1.3-1.52) and 1.13 (95%CI: 1.10-1.18) respectively. In comparative studies in RA adherence to infliximab was better than etanercept and etanercept did better than adalimumab. In three studies, the most consistent factor associated with lower adherence was female gender. Results for age, immunomodulator use and prior TNF-α inhibitors use were conflicting.

CONCLUSION: One-third of both CD and RA patients treated with TNF-α inhibitors are non-adherent. Female gender was consistently identified as a negative determinant of adherence.

Keywords: Adherence; Tumor necrosis factor-α inhibitors; Systematic review; Crohn’s disease; Rheumatoid arthritis

Core tip: This study assessed adherence with tumor necrosis factor-α (TNF-α) inhibitors in Crohn’s disease (CD) and rheumatoid arthritis (RA) by systematic review. We found only two-third of the patients with CD and RA receiving TNF-α inhibitors adherent to therapy. Definitions of measurement of adherence varied widely between studies and there is no clarity on what levels of adherence are required for optimal results of therapy. Future research on adherence should focus on therapy outcome, by using uniform definitions of adherence.