Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.