Endoscopy 2011; 43(10): 928
DOI: 10.1055/s-0030-1256697
Letters to the editor

© Georg Thieme Verlag KG Stuttgart · New York

Tocilizumab-induced intestinal injury

K.  Hagiwara
Further Information

Publication History

Publication Date:
07 October 2011 (online)

I read with great interest the article by Dr. Iwasa and colleagues about the patient who developed multiple ulcers in the intestines during therapy for rheumatoid arthritis with tocilizumab, a monoclonal antibody against human interleukin-6 (IL-6) receptor [1]. The temporal relationship between unexpected re-administration of tocilizumab and recurrence of hematochezia is convincing. Recently, I treated a 62-year-old woman with a 7-year history of refractory rheumatoid arthritis, who developed massive hematochezia 1 day after the first administration of tocilizumab. Endoscopic examination revealed bleeding from multiple diverticula in the large intestine. Similarly, the patient experienced recurrence of hematochezia after unexpected re-administration of tocilizumab.

Although the mechanism of the development of tocilizumab-induced intestinal injury remains unclear, Dr. Iwasa and colleagues suggested the possibility that blockade of IL-6 signaling by tocilizumab impaired tissue repair of the gut mucosa and caused intestinal ulcers [2]. I consider that IL-6 plays an essential role in intestinal tissue repair, as Dr. Jin and colleagues have clearly demonstrated that IL-6 inhibits intestinal epithelial cell death in mice. In particular, those authors revealed increased intestinal cell injury in IL-6-null mice, suggesting that endogenous IL-6 plays an essential and specific role [3]. If such a cytoprotective effect of IL-6 on intestinal epithelial cells is also essential and specific in humans, inhibition of IL-6 signaling may result in impaired intestinal tissue repair after an ulcerative lesion has formed. I would highly recommend that endoscopic examination be performed in all patients before starting the IL-6 inhibitor, and that administration of IL-6 inhibitor be avoided in patients with any intestinal lesions.

References

  • 1 Iwasa T, Nakamura K, Ogino H et al. Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis.  Endoscopy. 2011;  43 70-72
  • 2 Tebbutt N C, Giraud A S, Inglese M et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice.  Nat Med. 2002;  8 1089-1097
  • 3 Jin X, Zimmers T A, Zhang Z et al. Interleukin-6 is an important in vivo inhibitor of intestinal epithelial cell death in mice.  Gut. 2010;  59 186-196

K. HagiwaraMD, PhD 

Department of Allergy and Rheumatology
Japanese Red Cross Medical Center

4-1-22 Hiroo, Shibuya-ku
Tokyo 150-8935

Japan

Fax: +81-3-34091604

Email: hagiwarak-tky@umin.ac.jp

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