P0860 Long-term outcomes of extended versus conventional adalimumab dose interval for patients with Crohn’s disease in stable remission: 3-year follow-up of the randomized controlled LADI trial
Authors: Devillers M , van Lierop L , van Linschoten R , Jansen F , den Broeder N , de Jong D , Bodelier A , West R , Gisbertz I , Römkens T , Boekema P , Lutgens M , Mujagic Z , Wolfhagen F , de Boer N , Oldenburg B , van Bodegraven A , Mallant-Hent R , van der Meulen-de Jong A , ter Borg P , Braat H , Jansen J , Tan A , Jansen S , van der Woude J , de Vries A , Hoentjen F 
Published: January 2025

Abstract

Background
In the randomized controlled LADI trial, a subset of patients with Crohn’s disease (CD) maintained clinical remission following extension of the adalimumab dose interval (1). The aim of this study was to assess long-term clinical outcomes for trial participants who extended the adalimumab interval to 3 or 4 weeks compared to conventional dosing.

Methods
At baseline, we enrolled CD patients in biochemical and corticosteroid-free clinical remission (CFCR) on adalimumab 40 mg/2 weeks. The intervention group started on a 3-week interval and increased to 4 weeks at week 24, if in clinical and biochemical remission. Controls remained on adalimumab 40 mg/2 weeks. Data &gt;48 weeks was collected between 2017 and 2023. The primary endpoint of the current study was the proportion of patients in CFCR (HBI ≤4 or remission per physician global assessment) at year 3 while maintaining the assigned baseline adalimumab interval (intervention: 40 mg/3-4 weeks, control: 40 mg/2 weeks). Secondary endpoints included biochemical remission (CRP ≤10 mg/L and/or FC ≤250 µg/g), proportion of patients who discontinued adalimumab for stable remission, and adverse events (AEs). Patients without sufficient long-term data were excluded.

Results
Data was extracted for 143/174 initially randomized subjects (intervention: 95; control: 48). Figure 1 is a Sankey diagram for visualization of patient flow during follow-up. In the intervention group, 30/95 (31.6%) patients maintained de-escalation at 3 years (7 on a 3-week interval, 23 on a 4-week interval) while 4 patients stopped for stable remission. The primary endpoint of CFCR was achieved in 28/95 (29.5%) at year 3, and 23/95 (24.2%) were in biochemical remission. Twenty-eight patients re-escalated to 40 mg/2 weeks, 24/28 were in CFCR at year 3. In the control group, 30/48 (62.5%) patients maintained the 2-week interval after 3 years with 27/48 (56.3%) in CFCR, and 20/48 (41.7%) in biochemical remission. In addition to 4 subjects in each group that stopped adalimumab for stable remission, another 19 patients (13.3%) discontinued adalimumab by year 3 (intervention: n=17/95 (17.9%); control: n=2/48 (4.2%)). Discontinuation reasons were loss of response (n=9, 50.0% (8 in intervention group)), AEs (n=5, 27.8%), adalimumab antibodies (n=4, 22.2%, 3 in intervention group), and 1 missing. AEs are shown in Table 1.

Conclusion
Long-term follow-up showed that one-third of patients in the intervention group was in remission after continued de-escalation of adalimumab therapy at year 3, while another 25% recaptured remission after dose re-escalation. In the control group, over half of patients maintained remission on adalimumab every 2 weeks.

References
1.van Linschoten RCA, Jansen FM, Pauwels RWM, Smits LJT, Atsma F, Kievit W, et al. Increased versus conventional adalimumab dose interval for patients with Crohn’s disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023;8(4):343-55.