P0914 Clinical outcomes of dose-escalated adalimumab in Inflammatory Bowel Disease: A retrospective tertiary centre experience
Authors: Terlato M , Salehi O , Gondal F , Pillay L , Macrae F , Rentsch C , Dimovski S , Segal J P 
Published: January 2025

Abstract

Background
Despite anti-tumour necrosis factor-α agents (anti-TNF-α) – infliximab (IFX) and adalimumab (ADA) changing the landscape of inflammatory bowel disease (IBD) treatments over the last decade, their use is limited by secondary loss of response (SLOR).1 Anti-TNF-α dose escalation is frequently employed in patients with SLOR and/or low drug levels.2-3 The long-term effectiveness and safety of dose-escalated ADA remains unclear. Hence, we evaluated clinical outcomes following ADA dose escalation in a tertiary centre IBD cohort. We aimed to determine the effectiveness and safety of dose-escalated ADA in IBD patients who had inadequate response to standard dosing ADA after initial response and in patients undergoing escalated induction.

Methods
We conducted a retrospective analysis of IBD patients who underwent ADA dose escalation between 2018-2024 at a tertiary IBD centre. Dose escalation was defined as an increase in dose (&gt; 40 mg) and/or frequency [&gt; every 2 weeks (Q2W)]. Primary outcomes included clinical improvement (HBI), biochemical markers (CRP, faecal calprotectin), and treatment persistence, assessed at 3-12 months and annually up to 3 years following dose escalation. Secondary outcomes included adverse events (AE).

Results
A total of 50 patients (median age 35 years, 48% female) were included, of which 47 patients (94%) had Crohn’s disease (CD) and 3 patients (6%) had ulcerative colitis (UC) (Figure 1). Indications for dose escalation included SLOR (36/50; 72%), low drug levels (10/50; 20%) and escalated induction following failure of an alternative biologic therapy (4/50; 8%). Dose-escalated ADA led to a significant improvement in HBI at 3-12 months (p=0.018). This improvement was maintained at 12 months (p=0.009) and 2 years (p=0.010). Significant initial improvements in biochemical markers were reported at 3-12 months (CRP: p=0.048; faecal calprotectin: p=0.023). These improvements were not maintained at any further follow-up points (p&gt;0.05). Treatment persistence was high at 3-12 months (82%), however, only 45% of patients persisted at 3 years. Persistence was higher for biologic-naïve patients (56%) compared with biologic-exposed patients (37%) at 3 years. Four patients reported AE. Urticaria around the injection site (n=2) led to discontinuation in a single patient. Other AE included rheumatological symptoms (n=1) and recurrent catheter-associated urinary tract infections (n=1), the latter prompting de-escalation.

Conclusion
Dose-escalated ADA appears to be an effective and safe strategy for achieving sustained clinical improvements and early biochemical improvements in IBD patients. Higher persistence in biologic-naïve patients suggests that this strategy may be more effective in this group.

References
1. J Crohn’s Colitis. 2010 Oct 1;4(4):355-66. doi: 10.1016/j.crohns.2010.04.004
2. J Gastroenterol. 2017 May;52:535-54. doi: 10.1007/s00535-017-1324-3
3. Crohn’s & Colitis 360. 2023 Oct 1;5(4):otad061. doi: 10.1093/crocol/otad061