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* = Presenting author

OP011 Comparison of adalimumab monotherapy and a combination with azathioprine for patients with Crohns disease: a prospective, multicentre, open-labelled clinical trial (DIAMOND study)

T. Matsumoto*1, S. Motoya2, K. Watanabe3, T. Hisamatsu4, H. Nakase5, N. Yoshimura6, T. Ishida7, S. Kato8, T. Nakagawa9, M. Esaki10, M. Nagahori11, T. Matsui12, Y. Naito13, T. Kanai14, Y. Suzuki15, M. Nojima16, M. Watanabe11, T. Hibi17

1Iwate Medical University, Division of Gastroenterology, Department of Medicine, Morioka, Japan, 2Sapporo Kosei General Hospital, Inflammatory Bowel Disease Centre, Sapporo, Japan, 3Osaka City General Hospital, Division of Gastroenterology, Osaka, Japan, 4Kyorin University School of Medicine, The Third Department of Internal Medicine, Tokyo, Japan, 5Kyoto University, Department of Gastroenterology and Hepatology, Endoscopic Medicine, Kyoto, Japan, 6Tokyo Yamate Medical Centre, Department of Medicine, Division of Gastroenterology, Tokyo, Japan, 7Oita Red Cross Hospital, Department of Gastroenterology, Oita, Japan, 8Saitama Medical Centre, Saitama Medical University, Department of Gastroenterology and Hepatology, Kawagoe, Japan, 9Chiba University, Department of Gastroenterology and Nephrology (K1), Graduate School of Medicine, Chiba, Japan, 10Kyushu University, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Fukuoka, Japan, 11Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Tokyo, Japan, 12Fukuoka University Chikushi Hospital, Department of Gastroenterology, Chikushino, Japan, 13Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Department of Molecular Gastroenterology and Hepatology, Kyoto, Japan, 14Keio University, Department of Internal Medicine, School of Medicine, Tokyo, Japan, 15Toho University Sakura Medical Centre, Department of Internal Medicine, Sakura, Japan, 16The Institute of Medical Science Hospital, The University of Tokyo, Centre for Translational Research, Tokyo, Japan, 17Kitasato University Kitasato Institute Hospital, Centre for Advanced IBD Research and Treatment, Tokyo, Japan

Background

The efficacy and safety profiles of simultaneous azathioprine use for Crohn’s disease under adalimumab treatment remain obscure.

Methods

In this prospective, randomised, multicentre, open-labelled trial, we evaluated the efficacy of adalimumab with and without azathioprine in 177 Japanese patients with moderate-to-severe Crohn’s disease, who were naïve to biologics and thiopurines. Patients were randomly assigned to subcutaneous administration of adalimumab (160 mg at week 0, 80 mg at week 2, and subsequently 40 mg at every other week) (monotherapy group) or to exactly the same schedule of adalimumab with azathioprine (25–100 mg daily) (combination group) for 52 weeks. Primary endpoint was clinical remission at 26 weeks. Moderate-to-severe Crohn’s disease was defined as a Crohn’s disease activity index (CDAI) of 220~450 and remission as CDAI < 150. Score for simple endoscopic severity of Crohn’s disease (SES-CD) was determined before therapy and at 26 and 52 weeks. Endoscopic improvement was determined as SES-capsule endoscopy (CE) ≤ 4 points or a decrease in SES-CD ≥ 8 points.

Results

Of 177 patients recruited for the study, 176 patients were randomised to either the monotherapy group (n = 85) or to the combination group (n = 91). Sixty-three patients in the monotherapy group (74.1%) and sixty-two patients in the combination group (68.1%) completed the study (p = 0.51). Eighteen patients (21.2%) in the monotherapy group and 7 patients (7.7%) in the combination group withdrew because of active disease. In contrast, 15 patients (16.5%) in the combination group and 2 patients (2.4%) in the monotherapy group withdrew because of side effects of the medication. An intention-to-treat analysis with nonresponder imputation demonstrated that the remission rate at 26 weeks was not significantly different between the monotherapy group and the combination group (71.8% vs 68.1%; OR 0.84, p = 0.63). The rate of endoscopic improvement at 26 weeks was significantly higher in the combination group (84.2%, n = 57) than in the monotherapy group (63.8%, n = 58) (p = 0.019). Pharmacokinetic analyses of adalimumab at 26 weeks showed trends towards higher trough levels of adalimumab (7.56 ± 3.59 µg/ml vs 6.50 ± 3.86 µg/ml, p = 0.084) and lower prevalence of antibody to adalimumab (4.0% vs 13.2%, p = 0.078) in the combination group than in the monotherapy group. Limitations: This was an open-labelled study.

Conclusion

Clinical efficacy of a combination of adalimumab and azathioprine at 26 weeks was not significantly different from that of adalimumab monotherapy in patients with Crohn’s disease naïve to both medications. The combination therapy led to the significantly better endoscopic improvement than monotherapy did.