Scandinavian Journal of Gastroenterology. 2014; 49: 1270–1271

LETTER TO THE EDITOR

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Two cases of ulcerative colitis developing in rheumatoid arthritis patients during abatacept therapy

RENA MOTOHASHI, HIDEKAZU IKEUCHI, KEIJU HIROMURA, YUKO OHISHI, NORIYUKI SAKURAI, TORU SAKAIRI, YORIAKI KANEKO, AKITO MAESHIMA & YOSHIHISA NOJIMA Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

To the Editor Anti-TNF-a antibody, which is widely used for rheumatoid arthritis (RA), is also effective in patients with ulcerative colitis (UC) who exhibit an insufficient response to conventional therapy. In contrast, a recent placebo-controlled trial has demonstrated that abatacept, another biological agent for RA (consisting of a fusion protein composed of the Fc region of IgG and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) [CTLA-4Ig]), is not efficacious for the treatment of moderate-to-severe UC [1]. Because prophylactic treatment with abatacept was effective in an animal model of colitis, but failed to induce remission in humans with established colitis [2], the failure of abatacept in the human trial may be due to the timing of administration [3]. Here, we present two patients with RA in whom UC developed after the administration of abatacept. Case 1, a 24-year-old woman, was diagnosed as having RA based on a positive result for anti-cyclic citrullinated peptide (CCP) antibodies and polyarthritis. Combination therapy with methotrexate (MTX) and abatacept induced a clinical remission in 3 months. About 23 months after the initiation of abatacept, she developed diarrhea with blood. A diagnosis of UC was made based on the results of a colonoscopy (Figure 1A) and a histological analysis (Figure 1B). Infliximab and mesalazine were administered after the cessation of MTX and abatacept.

Case 2, a 21-year-old woman, had polyarthritis and a positive result for anti-CCP antibodies. She was diagnosed as having RA and entered clinical remission after 5 months of combination therapy with MTX and abatacept. At the time of remission, diarrhea and bloody stools appeared, and she became progressively anemic. A colonoscopy and biopsy were performed, and she was diagnosed as having UC (Figure 1C and D). She was treated with mesalazine, prednisolone, and granulocytapheresis, together with the discontinuation of abatacept and MTX. Although the coexistence of RA and other autoimmune disorders, such as Sjögren’s syndrome and autoimmune thyroiditis, is common, the association of UC and RA is rare and has been infrequently reported in the literature [3–7]. One of the reasons for the infrequent association is thought to be that UC and RA tend to share efficacious drugs, such as sulfasalazine and corticosteroids [7]. As a new agent, anti-TNF-a antibody has been shown to be effective against both diseases. The prevalence of RA and UC are relatively high in Japan (>700,000 and >100,000), respectively. Therefore, there is a possibility that this coexistence is by chance. However, the early development of UC in RA patients after the initiation of abatacept treatment suggests that abatacept therapy triggered UC. In addition to our two cases, Amezcua-Guerra also reported a patient who developed UC during

Correspondence: Hidekazu Ikeuchi, MD, PhD, Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan. Tel: +81 27 220 8166. Fax: +81 27 220 8173. E-mail: [email protected]

(Received 6 July 2014; accepted 11 July 2014) ISSN 0036-5521 print/ISSN 1502-7708 online  2014 Informa Healthcare DOI: 10.3109/00365521.2014.946087

Ulcerative colitis during abatacept A

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strongly suggest that abatacept, at the very least, is not effective for preventing the development of UC in RA patients. In addition, UC complications should be considered when diarrhea and bloody stools are observed in RA patients during abatacept treatment. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

References

Figure 1. Finding of colonoscopy and rectal biopsy is shown. A loss of vascularity in the colon, together with friable and granular mucosal changes, was observed during a colonoscopy. A rectal biopsy showed neutrophil infiltration in the mucosa and crypt abscesses (hematoxylin and eosin staining, 100). (A) and (B) show case 1; (C) and (D) show case 2.

abatacept therapy for RA [8]. In that report, a 55-year-old man with a 7-year history of seropositive RA developed UC 15 months after the initiation of abatacept treatment. One might expect that blocking the interaction of CD80/CD86 on antigen-presenting cells and CD28 on T lymphocytes by CTLA-4Ig not only prevents the activation of T lymphocytes but also alters both the development and maintenance of regulatory T cells [8]. Although the causative role of abatacept in the induction of UC in RA patients remains uncertain, our two cases combined with previous reports

[1] Sandborn WJ, Colombel JF, Sands BE, Rutgeerts P, Targan SR, Panaccione R, et al. Abatacept for Crohn’s disease and ulcerative colitis. Gastroenterology 2012;143:62–9.e4. [2] Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyteassociated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 2000;192:295–302. [3] Boyer F, Fontanges E, Miossec P. Rheumatoid arthritis associated with ulcerative colitis: a case with severe flare of both diseases after delivery. Ann Rheum Dis 2001;60:901. [4] Adachi Y, Hinoda Y, Takahashi H, Nakagawa N, Sakamoto H, Itoh F, et al. Rheumatoid arthritis associated with ulcerative colitis. J Gastroenterol 1996;31:590–5. [5] Sugisaki K, Honma F, Iwadate H, Shio K, Shioya Y, Fukaya E, et al. Ulcerative colitis occurring in the course of rheumatoid arthritis: a case successfully treated with mesalamine enema. Intern Med 2004;43:1046–50. [6] Asada Y, Isomoto H, Shikuwa S, Wen CY, Fukuda E, Miyazato M, et al. Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency. World J Gastroenterol 2006;12:5240–3. [7] Cruz VA, Yamaguchi L, Ribeiro CN, Magalhaes Vde O, Rego J, Silva NA. Ulcerative colitis and rheumatoid arthritis: a rare association–case report. Rev Bras Reumatol 2012;52: 648–50. [8] Amezcua-Guerra LM, Hernandez-Martinez B, Pineda C, Bojalil R. Ulcerative colitis during CTLA-4Ig therapy in a patient with rheumatoid arthritis. Gut 2006;55:1059–60.

Two cases of ulcerative colitis developing in rheumatoid arthritis patients during abatacept therapy.

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