Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Early Initiation of Adalimumab Significantly Diminishes Post-operative Crohn’s Disease Endoscopic Recurrence and Is Superior to 6-Mercaptopurine Therapy. An Open Label Randomized Controlled Study

Ayal Hirsch
† ORCID logo ,
Erez Scapa
† ,
Naomi Fliss Isakov
ORCID logo ,
Hagit Tulchinsky
,
Eran Itzkowitz
,
Yehuda Kariv
,
Yulia Ron
,
Henit Yanai
,
Ian White
,
Sharif Yassin
,
Nathaniel Aviv Cohen
,
Eli Brazovski
,
Iris Dotan
† ,
Nitsan Maharshak
*,†
†
These authors contributed equally to these manuscript.
Version 1 : Received: 24 October 2023 / Approved: 25 October 2023 / Online: 25 October 2023 (10:04:57 CEST)

A peer-reviewed article of this Preprint also exists.

Hirsch, A.; Scapa, E.; Fliss-Isakov, N.; Tulchinsky, H.; Itzkowitz, E.; Kariv, Y.; Ron, Y.; Yanai, H.; White, I.; Yassin, S.; Cohen, N.A.; Brazovski, E.; Dotan, I.; Maharshak, N. Early Initiation of Adalimumab Significantly Diminishes Postoperative Crohn’s Disease Endoscopic Recurrence and Is Superior to 6-Mercaptopurine Therapy: An Open-Label, Randomized Controlled Study. J. Clin. Med. 2023, 12, 7600. Hirsch, A.; Scapa, E.; Fliss-Isakov, N.; Tulchinsky, H.; Itzkowitz, E.; Kariv, Y.; Ron, Y.; Yanai, H.; White, I.; Yassin, S.; Cohen, N.A.; Brazovski, E.; Dotan, I.; Maharshak, N. Early Initiation of Adalimumab Significantly Diminishes Postoperative Crohn’s Disease Endoscopic Recurrence and Is Superior to 6-Mercaptopurine Therapy: An Open-Label, Randomized Controlled Study. J. Clin. Med. 2023, 12, 7600.

Abstract

Post operative recurrence (POR) is the rule in patients with Crohn’s disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single center randomized open label clinical study, in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 post-operatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score≥i2. We enrolled 35 patients (25 males, mean age 35±1.4 years, median disease duration 5±6.1 years) following ileocecectomy. Of these, 7(20%) were current smokers and 9(26%) biologics experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs 69%, p=0.004) and 58 (47% vs 75%), (p=0.03, HR=0.39, 95% CI=0.16-0.93). POR was associated with increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin and serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab is more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower post-operative BMI were associated with ePOR. Eighteen weeks serum hemoglobin and ALT, and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

Keywords

clinical trial; crohn; surgery; 6-mercaptopurine; adalimumab

Subject

Medicine and Pharmacology, Gastroenterology and Hepatology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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