P858 Real World Outcomes of Dual Advanced Therapy in Inflammatory Bowel Disease in Children and Young Adults

Abstract

Abstract Background There is mounting interest in dual advanced therapy (DAT), combining 2 biologics or biologics with small molecules, in patients with refractory disease or partial responders. We evaluated the real-world efficacy and safety of DAT in pediatric and young adults with IBD. Methods Single-center, cross-sectional cohort study, conducted between 2018-2023. Primary outcome was DAT remission (clinical (Harvey Bradshaw Index ≤ 4 or partial Mayo Score ≤ 2) and biomarker (C-reactive protein ≤ 5 mg/L and/or fecal calprotectin ≤ 250 ug/g) at first efficacy assessment (T1). Secondary outcomes included remission at T2 if intensification or de-intensification occurred at T1 and T3 remission if re-intensification performed at T2. Failures defined those not achieving remission. Adverse events, surgical and therapy outcomes as of last follow up were evaluated. Descriptive statistics summarized the data. Results 30 patients were included [43% female, 57% CD, median age of 18.3 [15.1-19.8] years, 46% <18 years, and median IBD duration of 5.2 [4.0-6.9] years at DAT start] (Table 1). Of 11 (37%) treated with TOFA + UST, 100% achieved T1 remission. Of the 10 de-intensified at T1, 6 failed at T2, and all 4/6 that re-intensified achieved T3 DAT remission. Of 9 (30%) TOFA + VDZ patients, 6 (67%) achieved T1 remission and of the 3 T1 failures, 1 had colectomy, and 1 of 2 attempting VDZ intensification achieved T2 remission. All 6 with T1 remission de-intensified, but 5 (83%) failed and only 1/5 attempted re-intensification and failed. Of 4 (13%) VDZ + UST patients, 3 (75%) achieved T1 remission and the 1 T1 failure achieved T2 remission after VDZ intensification. The 2/4 de-intensified failed at T2 and none were re-intensified. Of 5 (17%) UPA + UST patients, 4 (80%) achieved T1 DAT remission and the 1 failure achieved T2 remission after UPA intensification. The 1 who de-intensified failed at T2 but in T3 remission post re-intensification. One (3%) VDZ + OZA patient achieved T1 remission and successfully de-intensified to monotherapy OZA at T2. One TOFA + UST patient developed mild leukopenia and responded to TOFA de-intensification, and 1 developed septic arthritis on TOFA +VDZ on prednisone and resumed TOFA once resolved. At last follow-up, 14/30 (47%) patients were on DAT, 11 (37%) changed therapy, 1 of which underwent colectomy and 5 (17%) were on monotherapy (Figure 1). Conclusion The majority of IBD patients treated with DAT achieved clinical and biomarker remission with minimal safety events; however, de-intensification to monotherapy has limited success and supports continuing DAT in more refractory patients. Future studies are needed to guide management.