PMID- 35310082 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240218 IS - 2631-827X (Electronic) IS - 2631-827X (Linking) VI - 4 IP - 1 DP - 2022 Jan TI - Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease. PG - otac002 LID - 10.1093/crocol/otac002 [doi] LID - otac002 AB - 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. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation. FAU - Alayo, Quazim A AU - Alayo QA AUID- ORCID: 0000-0001-5524-7105 AD - Department of Internal Medicine, St. Luke's Hospital, St. Louis, Missouri, USA. AD - Division of Gastroenterology and Inflammatory Bowel Diseases Centre, Washington University in Saint Louis School of Medicine, St. Louis, Missouri, USA. FAU - Fenster, Marc AU - Fenster M AD - Division of Gastroenterology, Albert Einstein College of Medicine, Montefiore Medical Centre, Bronx, New York, USA. FAU - Altayar, Osama AU - Altayar O AD - Division of Gastroenterology, Washington University in Saint Louis School of Medicine, St. Louis, Missouri, USA. FAU - Glassner, Kerri L AU - Glassner KL AD - Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Houston, Texas, USA. FAU - Llano, Ernesto AU - Llano E AD - Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA. FAU - Clark-Snustad, Kindra AU - Clark-Snustad K AD - Division of Gastroenterology, University of Washington Medical Centre, Seattle, Washington, USA. FAU - Patel, Anish AU - Patel A AD - Division of Gastroenterology, Brooke Army Medical Centre, Fort Sam Houston, Texas, USA. FAU - Kwapisz, Lukasz AU - Kwapisz L AD - Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA. FAU - Yarur, Andres J AU - Yarur AJ AD - Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. FAU - Cohen, Benjamin L AU - Cohen BL AD - Department of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Ciorba, Matthew A AU - Ciorba MA AD - Division of Gastroenterology and Inflammatory Bowel Diseases Centre, Washington University in Saint Louis School of Medicine, St. Louis, Missouri, USA. FAU - Thomas, Deborah AU - Thomas D AD - Bernard Becker Medical Library, Washington University in Saint Louis, St. Louis, Missouri, USA. FAU - Lee, Scott D AU - Lee SD AD - Division of Gastroenterology, University of Washington Medical Centre, Seattle, Washington, USA. FAU - Loftus, Edward V Jr AU - Loftus EV Jr AD - Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. FAU - Fudman, David I AU - Fudman DI AD - Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA. FAU - Abraham, Bincy P AU - Abraham BP AD - Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Houston, Texas, USA. FAU - Colombel, Jean-Frederic AU - Colombel JF AUID- ORCID: 0000-0001-6472-249X AD - Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Deepak, Parakkal AU - Deepak P AUID- ORCID: 0000-0002-3436-9784 AD - Division of Gastroenterology and Inflammatory Bowel Diseases Centre, Washington University in Saint Louis School of Medicine, St. Louis, Missouri, USA. LA - eng GR - P30 DK052574/DK/NIDDK NIH HHS/United States GR - T32 DK007745/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20220210 PL - England TA - Crohns Colitis 360 JT - Crohn's & colitis 360 JID - 101752188 PMC - PMC8924906 OTO - NOTNLM OT - Crohn's disease OT - biologics OT - inflammatory bowel diseases OT - meta-analysis OT - ulcerative colitis EDAT- 2022/03/22 06:00 MHDA- 2022/03/22 06:01 PMCR- 2022/02/10 CRDT- 2022/03/21 08:58 PHST- 2021/05/04 00:00 [received] PHST- 2022/03/21 08:58 [entrez] PHST- 2022/03/22 06:00 [pubmed] PHST- 2022/03/22 06:01 [medline] PHST- 2022/02/10 00:00 [pmc-release] AID - otac002 [pii] AID - 10.1093/crocol/otac002 [doi] PST - epublish SO - Crohns Colitis 360. 2022 Feb 10;4(1):otac002. doi: 10.1093/crocol/otac002. eCollection 2022 Jan.