DOP071 Comparison of endoscopic responses to adalimumab monotherapy and combination therapy with azathioprine in patients with Crohn's disease: a sub-analysis of DIAMOND trial
Watanabe K.*1, Matsumoto T.2, Motoya S.3, Hisamatsu T.4, Nakase H.5, Yoshimura N.6, Ishida T.7, Kato S.8, Nakagawa T.9, Nagahori M.10, Esaki M.11, Matsui T.12, Naito Y.13, Kanai T.14, Suzuki Y.15, Nojima M.16, Watanabe M.10, Hibi T.17
1Osaka City General Hospital, Gastroenterology, Osaka, Japan 2Iwate Medical University, Division of Gastroenterology, Department of Medicine, Morioka, Japan 3Sapporo Kosei General Hospital, Inflammatory Bowel Disease Centre, Sapporo, Japan 4Kyorin University School of Medicine, Department of Internal Medicine, Tokyo, Japan 5School of Medicine, Sapporo Medical University, Department of Gastroenterology and Hepatology, Sapporo, 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 9Graduate School of Medicine, Chiba University, Department of Gastroenterology and Nephrology, Chiba, Japan 10Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Tokyo, Japan 11Graduate School of Medical Sciences, Kyushu University, Department of Medicine and Clinical Science, Fukuoka, Japan 12Fukuoka University Chikushi Hospital, Department of Gastroenterology, Fukuoka, Japan 13Kyoto Prefectural University of Medicine, Department of Molecular Gastroenterology and Hepatology, Kyoto, Japan 14School of Medicine, Keio University, Department of Internal Medicine, Tokyo, Japan 15Toho University Sakura Medical Center, Department of Internal Medicin, Chiba, Japan 16Institute of Medical Science Hospital, University of Tokyo, Centre for Translational Research, Tokyo, Japan 17Kitasato University Kitasato Institute Hospital, Centre for Advanced IBD Research and Treatment, Tokyo, Japan
We recently reported the results of a prospective, randomized controlled trial comparing the efficacy of adalimumab (ADA) monotherapy and a combination therapy with azathioprine (AZA) for patients with Crohn's disease (CD), who were naïve to biologics and thiopurines (DIAMOND trial). This sub-analysis aims to evaluate endoscopic response and mucosal healing at week 26 and 52 in patients enrolled for the trial.
In the preceding DIAMOND trial, 176 patients were randomly assigned to either ADA monotherapy or ADA in combination with AZA. The data for SES-CD were available for 115 patients at week 26 and for 102 patients at week 52. Among 41 patients with adverse events, 25 patients who withdrew the trial due to CD worsening were regarded as endoscopic non-responders (non-responder imputation), while 16 patients who discontinued the study drug were excluded from the analysis. Endoscopic response was defined as a decrease in the SES-CD of at least 8 points from the baseline, or SES-CD ≤4. Mucosal healing was defined as SES-CD ≤2.
Endoscopic response rate at week 26 was significantly higher in the combination group than in the monotherapy group (OR=2.12, 95% CI 1.036–4.323, p=0.05), while the rate at week 52 was not different between the two groups (OR=1.50, 95% CI 0.765–2.942, p=0.31). The rate of mucosal healing was different between the two groups neither at week 26 (OR=2.30, 95% CI 0.865–6.128, p=0.10) nor at week 52 (OR=1.98, 95% CI 0.795–4.946, p=0.17). There were statistically significant associations between mucosal healing at week 26 and CDAI at week 0 (OR=1.01, 95% CI 1.000–1.024, p=0.05) and between mucosal healing at week 26 and SES-CD at week 0 (OR=0.80, 95% CI 0.716–0.898, p<0.01). Similar trends were also found between mucosal healing at week 52 and CDAI (OR=1.01, 95% CI 1.004–1.024, p<0.01) and SES-CD (OR=0.91, 95% CI 0.838–0.980, p=0.01) at week 0. The serum ADA concentration at week 26 was significantly higher in patients with endoscopic response than those without at week 26 (8.20±3.55 μg/ml vs. 4.89±3.10 μg/ml, p<0.001) and at week 52 (8.16±3.68 μg/ml, vs. 5.35±3.38 μg/ml, p<0.001). Among four items belonging to SES-CD, stricture improved less frequently than the other three items at week 26 and at week 52, and there were no difference for this trend between monotherapy group and combination group.
In DIAMOND trial, concomitant AZA had marginal effects on endoscopic response while there was a significant association between ADA concentration and endoscopic response. For patients with CD treated by ADA, the use of concomitant AZA should be optimized on the basis of the clinical course and endoscopic findings especially for stricture.