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. 2023 Dec 10;12(24):7600.
doi: 10.3390/jcm12247600.

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

Ayal Hirsch  1 , Erez Scapa  1   2 , Naomi Fliss-Isakov  1 , Hagit Tulchinsky  2   3 , Eran Itzkowitz  2   3 , Yehuda Kariv  2   3 , Yulia Ron  1 , Henit Yanai  2   4 , Ian White  2   5 , Sharief Yassin  1 , Nathaniel Aviv Cohen  1 , Eli Brazovski  2   6 , Iris Dotan  2   4 , Nitsan Maharshak  1   2
Affiliations

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

Ayal Hirsch et al. J Clin Med. .

Abstract

Postoperative 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 the 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 postoperatively. 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, seven (20%) were current smokers and nine (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 an increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin, increased week 18 serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab was more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower postoperative BMI were associated with ePOR. At eighteen weeks, serum hemoglobin, ALT and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

Keywords: 6-mercaptopurine; Crohn; adalimumab; clinical trial; surgery.

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Conflict of interest statement

The authors received previously honoraria, speaking fees and educational and research grants from ABBVIE, the manufacturer of Humira and funder of this trial. Ayal Hirsch: honoraria, speaking fees and educational grant. Hagit Tulchinsky: speaking fees. Henit Yanai: Honoraria, speaking fees, consulting fees and participation in a data safety monitoring board or advisory board. Iris Dotan: honoraria, speaking fees and educational and research grants. Nitsan Maharshak: honoraria, speaking fees and educational and research grants. The funders had no role in the design of this study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Week 32 postoperative endoscopic recurrence by study arm (A), Kaplan-Meier curve of postoperative Crohn’s disease recurrence-free survival by study arm (B).
Figure 2
Figure 2
Forest plot of week 58 surgical recurrence hazard ratios (HR [95%CI]).
Figure 3
Figure 3
Fecal calprotectin concentration at week 18 predicts week 32 endoscopic recurrence.
Figure 4
Figure 4
BMI (A) and change in BMI from baseline (B) by week 58 endoscopic recurrence (Rutgeerts score > i2).
See this image and copyright information in PMC

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