Patel, Anish A

Abstract Background We aimed to evaluate the effectiveness and safety of risankizumab (RZB) for Crohn’s disease (CD) in routine clinical practice. Methods We performed a retrospective review of a multicenter consortium of CD patients treated with RZB. Co-primary outcomes were week 12 clinical remission (Harvey Bradshaw Index [HBI] score of ≤4 or physician global assessment in those without HBI or with ileostomy) and 6-month endoscopic remission (Simplified Endoscopic Mucosal Assessment for Crohn’s Disease of 0-1 or absence of ulcers). Secondary outcomes included steroid-free clinical remission, clinical response, radiographic response, cumulative clinical and endoscopic remission rates at 6 and 12 months, and adverse events. Results A total of 309 patients were included (median disease duration 14 years [IQR, 6-24]; median follow-up 7.1 months [IQR, 4.1-10.3]). Most patients (85.8%) were advanced therapy (AT)-exposed, and 169 (54.7%) had prior ustekinumab (UST) exposure. Week 12 clinical remission rates were 49.7% (98/197) overall, and 44.2% (50/113) vs 57.1% (48/84) in UST-exposed vs naïve patients (P = .073). Among those with active disease on baseline endoscopy (n = 122) who had an available follow-up at 6 months, 52.4% (22/42) achieved endoscopic remission. Cumulative rates of clinical and endoscopic remission at 12 months were 65.0% and 49.5%, respectively. Cumulative 12-month endoscopic remission was 33.9% (19/56) in UST-exposed and 68.1% (32/47) in UST-naïve patients (P < .001). Risankizumab was well-tolerated with no new safety signals identified. Conclusions In this large multicenter cohort of patients with CD, RZB was well-tolerated and effective in achieving favorable clinical and endoscopic outcomes in both AT-exposed and naïve populations, including those with exposure to UST.

Abstract Background Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC. Methods We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin. Results A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. Conclusions In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.

Abstract Background Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients. Methods We searched MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Clinical trials.gov until November 3, 2020, including studies with 2 or more IBD patients on DBT or SBT. Main outcome was safety assessed as pooled rates of adverse events (AEs) and serious AEs (SAEs) for each combination. Effectiveness was reported as pooled rates of clinical, endoscopic, and/or radiographic response and remission. The certainty of evidence was rated according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Results Of the 3688 publications identified, 13 studies (1 clinical trial, 12 observational studies) involving 266 patients on 7 different combinations were included. Median number of prior biologics ranged from 0 to 4, and median duration of follow-up was 16–68 weeks. Most common DBT and SBT were vedolizumab (VDZ) with anti-tumor necrosis factor (aTNF, n = 56) or tofacitinib (Tofa, n = 57), respectively. Pooled rates of SAE for these were 9.6% (95% confidence interval [CI], 1.5–21.4) for VDZ-aTNF and 1.0% (95% CI, 0.0–7.6) for Tofa-VDZ. The overall certainty of evidence was very low due to the observational nature of the studies, and very serious imprecision and inconsistency. Conclusions DBT or SBT appears to be generally safe and may be effective in IBD patients, but the evidence is very uncertain.

Abstract Background The level of inflammatory bowel disease (IBD) training in general gastroenterology fellowship is often insufficient to prepare trainees to deliver advanced IBD care in practice. Advanced IBD fellowships have been developed to fill this training gap, but there is no established curriculum, and significant variability exists across programs. Entrustable professional activities (EPAs) are practical and realistic objectives that define essential tasks of a specialty that physicians should master to be competent during independent practice. The American College of Gastroenterology (ACG) and Crohn’s & Colitis Foundation (Foundation) established a task force to develop and appraise EPAs for advanced IBD fellowship. Methods Entrustable professional activities were developed using a multistep approach in a similar manner to other specialties. Initial EPAs identified via focus groups were evaluated, critiqued, and changed using an iterative model of feedback. The final EPAs were selected after the task force conducted a 3-phase modified Delphi method consisting of 2 sequential rounds of web-based voting and an in-person consensus meeting. Results Ten EPAs for advanced IBD fellowship were established including detailed descriptions with the associated knowledge, skills, and attitudes for each that can serve as curricular milestones. Conclusion Ten EPAs describing the core work of an advanced IBD fellowship–trained physician have been established by a multisociety task force. Creating EPAs for an advanced curriculum comes with unique challenges, particularly the need to prevent duplication of prior training competencies while demonstrating the potential for unique milestones.