Gastroenterology. 2024 May;166(5):815-825.e22. doi: 10.1053/j.gastro.2024.01.041.Epub 2024 Feb 6.

Rona Lujan ¹, Rachel Buchuk ¹, Gili Focht ¹, Dotan Yogev ¹, Shira Greenfeld ², Amir Ben-Tov ², Yiska Loewenberg Weisband ³, Natan Lederman ⁴, Eran Matz ⁵, Shomron Ben Horin ⁶, Iris Dotan ⁷, Daniel Nevo ⁸, Dan Turner ⁹

Author information

¹Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology, and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.

²Kahn Sagol Maccabi Research and Innovation Center, Maccabi Health Services, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.

³Clalit Health Services, Clalit Research Institute, Tel Aviv, Israel.

⁴Meuhedet Health Insurance Fund, Medical Division, Tel Aviv, Israel.

⁵Leumit Health Services, Tel Aviv, Israel.

⁶Department of Statistics and Operations Research, Tel Aviv University, Israel.

⁷Sackler Faculty of Medicine, Tel Aviv University, Israel; Sheba Medical Center, Ramat Gan, Israel.

⁸Sackler Faculty of Medicine, Tel Aviv University, Israel; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel.

⁹Juliet Keidan Institute of Pediatric Gastroenterology, Hepatology, and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel. Electronic address: turnerd@szmc.org.il.

Abstract

Background & aims: In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC).

Methods: All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias.

Results: Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population.

Conclusions: Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.