P820 Targeting MM-SES-CD < 22.5 for endoscopic improvement is feasible in a clinical trial of Crohn’s disease: A post-hoc analysis of SEAVUE

Abstract

Abstract Background It has been demonstrated that a Modified Multiplier of the SES-CD (MM-SES-CD) < 22.5 is the optimal endoscopic threshold that is associated with a low risk of disease progression using data from the CALM long-term extension study. To determine whether or not this threshold would be a pragmatic target within the setting of a clinical trial, we performed a feasibility analysis using data from the phase 3 SEAVUE clinical trial. Methods We considered data from 373 patients from the SEAVUE clinical trial who had available endoscopic data at baseline and were treated with ustekinumab (n=187) or adalimumab (n=186). As participants were only required to have a single ulcer at the time of enrollment in SEAVUE, we further restricted the population to those with MM-SES-CD > 22.5. The primary outcome was MM-SES-CD < 22.5 at week 52. Secondary outcomes were common targets for endoscopic healing in clinical trials, including SES-CD reduction of ≥ 50%, SES-CD < 4, and SES-CD < 3. Clinical remission, defined as CDAI < 150, was also assessed at week 52. Sensitivity analyses were planned to restrict the population to those with moderate to severely active disease activity, defined as MM-SES-CD ≥ 31. Results Of the 373 participants, 55.2% (206/373) participants achieved a MM-SES-CD < 22.5. A total of 206 participants had a MM-SES-CD > 22.5 at baseline, of which 91 (44.2%) attained a MM-SES-CD < 22.5 at week 52. A greater proportion of participants achieved this outcome compared to SES-CD reduction of ≥ 50% (85/206, 41.3%), SES-CD < 4 (52/206, 25.2%), and SES-CD < 3 (36/206, 17.5%) at week 52 (Table 1). A total of 144 participants had moderate to severely active endoscopic disease at baseline (MM-SES-CD ≥ 31), of which 55 (38.2%) achieved a MM-SES-CD < 22.5 at week 52. This was similar to the number of patients who achieved SES-CD reduction of ≥ 50% (61/144, 42.4%), and greater than the number of patients who achieved SES-CD < 4 (34/144, 23.6%) or SES-CD < 3 (21/144, 14.6%) at week 52. Of the 144 participants with a MM-SES-CD ≥ 31 at baseline, a total of 71 received adalimumab and 73 received ustekinumab. Compared to adalimumab, a numerically greater proportion of those treated with ustekinumab achieved MM-SES-CD < 22.5 [33/71 (45.2%) vs. 22/71 (31%), p=0.079] and clinical remission [48/73 (65.8%) vs. 36/71 (50.7%), p=0.067] at week 52. Conclusion Based on this feasibility analysis, a MM-SES-CD < 22.5 is a feasible target to attain in clinical trials of Crohn’s disease. Further, use of the MM-SES-CD for measurement of endoscopic burden could lead to different conclusions being obtained from clinical trials of CD that are clinically and prognostically more relevant.