Real-World Outcomes of Dual Advanced Therapy in Inflammatory Bowel Disease
AIBD 2023
Background:
The efficacy of biologics and novel small molecules as monotherapy for the treatment of inflammatory bowel disease (IBD) is well-established. There is mounting interest in dual advanced therapy (DAT): combining two biologics, or a biologic and small molecule, particularly in patients with refractory disease. There is, however, limited real-world effectiveness and safety data supporting the use of DAT.
Methods:
Single-center, cross-sectional cohort study, conducted between 2018-2023 included IBD patients treated with DAT. Primary endpoint was DAT success at first efficacy assessment (T1). Secondary endpoints included success at 2nd efficacy assessment (T2) if intensified or de-intensification to monotherapy occurred at T1. For those who failed de-intensification at T2, DAT success of re-intensification was assessed at T3. Charts were reviewed to determine the efficacy criteria used to classify DAT success or failure at T1-T3: clinical response (HBI ≤4 or pMayo ≤2), biomarker remission (FCP ≤250 ug/g, C-reactive protein (CRP) ≤5 mg/L), endoscopic remission (SES-CD=0 or Mayo endoscopic score=0), and/or intestinal ultrasound (IUS) (bowel wall thickness < 3 mm and no hyperemia). Adverse events were recorded. Descriptive statistics summarized the data.
Results:
Of the 30 patients included [43% female with median age 18.3 [15.1-19.8] years; 17 (57%) CD]. Of 11 (37%) treated with TOFA + UST, 100% achieved T1 DAT success. Of the 10 that were de-intensified at T1, 6 failed at T2, and all 4/6 that re-intensified achieved T3 DAT success. Of 9 (30%) TOFA + VDZ patients, 6 (67%) patients achieved T1 DAT success and of the 3 T1 failures, 1 had colectomy, and 1 of 2 that attempted VDZ intensification achieved T2 DAT success. All 6 with T1 success de-intensified, but 5 (83%) failed and only 1 of 5 attempted re-intensification and failed at T3. Of 4 (13%) VDZ + UST patients, 3 (75%) achieved T1 DAT success and the 1 T1 failure achieved T2 success after VDZ intensification. The 2 who de-intensified failed at T2 and none were re-intensified. Of 5 (17%) UPA + UST patients, 4 (80%) achieved DAT success at T1 and the 1 T1 failure achieved T2 success after UPA intensification. The 1 patient who de-intensified failed at T2 but success at T3 re-intensification. One (3%) VDZ + OZA patient achieved T1 DAT success and successfully de-intensified to monotherapy OZA at T2. Efficacy assessment at T1 was based on clinical assessment (100%), biomarker (87%), IUS (23%), and endoscopy (17%). The most common assessment at T2 and T3 were clinical (100%), biomarker (100%), IUS (68%), and endoscopy (24%). One patient developed mild leukopenia on TOFA +UST and responded to TOFA dose de-intensification, and 1 developed septic arthritis on TOFA +VDZ while on prednisone and resumed TOFA once resolved.
Conclusions:
The majority of IBD patients treated with DAT achieve success; however, de-intensification to monotherapy has limited success and supports continuing DAT in refractory patients. Success, timing and durability of de-intensification and re-intensification remains unknown, and future studies are needed to guide management.
