Original articleDevelopment of inflammatory bowel disease during anti-TNF-α therapy for inflammatory rheumatic disease. A nationwide series
Introduction
TNF-α antagonists have been shown to be highly effective in different inflammatory conditions, namely RA, AS, PsA, JIA, as well as psoriasis. Different anti-TNF-α drugs are currently available: infliximab and adalimumab are two anti-TNF-α monoclonal antibodies while etanercept is a p75 TNF-α receptor fusion protein. Another product is certolizumab pegol, which has been available for a few months in France and is a construct of anti-TNF-α Fab’ fragment linked to pegol residue. Anti-TNF-α monoclonal antibodies have also demonstrated their efficacy in IBD, and particularly in CD. In Europe and the USA, both infliximab and adalimumab are licensed for the treatment of CD, whereas etanercept was not shown to be effective in CD [1]. Infliximab is also effective in the treatment of UC.
Due to their high efficacy, TNF-α antagonists are used increasingly in IRD, psoriasis and IBD. Various side effects have been described, mainly infections. However, some unexpected and rare events that were not observed during the clinical trials of these drugs have emerged over the last few years: they are qualified as paradoxical because they occur after the initiation of the TNF-α blocking agent which is normally used to treat them [2]. These paradoxical events include new onset or exacerbation of psoriasis, development of aseptic granulomatous disease such as sarcoidosis [3], and appearance of uveitis or IBD [2].
This study was undertaken in order to better describe the clinical features of IBD occurring after the introduction of any TNF-α blocking agent in the French patient-population exposed to these drugs. We report here the largest series of patients under treatment with TNF-α antagonist developing new onset of IBD.
Section snippets
Methods
Between January 2009 and December 2010, all members of the “Club Rhumatismes and Inflammation (CRI)”, a section of the French Society of Rheumatology (Société française de rhumatologie [SFR]), including 2006 rheumatologists, internal medicine practitioners and pediatric rheumatologists, were regularly contacted via the CRI website system and by mail in order to collect information on all cases of patients with an IRD (RA, AS, PsA or JIA) who developed IBD while being treated with an anti-TNF-α
Patient demographics
Sixteen patients were reported, including nine men and seven women with a mean age of 41.5 ± (SD) 17.4 years (median 40.0). Three of these patients have been previously reported but individual details were not given [2]. The underlying IRD was AS in 12 cases, RA in one case, PsA in one case and JIA in two cases (including two patients with ERA). The mean disease duration was 13.7 ± 7.6 years (median: 12). Eight patients had extra-articular manifestations: uveitis in five cases and psoriasis in five
Discussion
We observed 16 cases of IBD after TNF-α blocker initiation, which represents the largest series nationwide. This series mainly included patients with AS or related spondylarthropathies (PsA or AS with juvenile onset or ERA) and only one patient with RA. There was a predominance of CD (50%) or CLD (43.7%) while UC was more rarely observed (6.25%). According to endoscopic findings, the extent of gastrointestinal involvement and the observance of pancolitis in combination with the occurrence of
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
Acknowledgements
The authors are indebted to Mrs. Frances Sheppard (CIC Biotherapy 506, Besançon, France) for help in preparing the manuscript and to Pr Jean Sibilia (Strasbourg, France), president of Le CRI, for critically reading the manuscript.
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Cited by (0)
- 1
Eric Toussirot is the main investigator who conceived and designed the study and drafted the manuscript. He contributed to the recruitment of the patients involved in the study and analyzed the results. Éric Houvenagel, Vincent Goëb, Damien Fouache, Antoine Martin, Philippe Le Dantec, Emmanuelle Dernis, Daniel Wendling, Thiphaine Ansemant, Jean-Marie Berthelot and Brigitte Bader-Meunier each contributed to the work as a clinical investigator by declaring one or more patient. Bernadette Kantelip provided histological results of two patients.
- 2
Le CRI: Club Rhumatismes and Inflammation, University Hospital St Antoine Paris, France.