Abstract Background The anti-TNF adalimumab (ADA) is effective in the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). However, a cumulative loss of response (LOR) occurs in 40–60% of patients within the first 3 years of therapy. This is commonly managed by dose escalation and therapeutic drug monitoring (TDM). However, baseline ADA drug levels mostly fail to differentiate between patients who will respond to dose intensification and those who will not. Fecal calprotectin correlates strongly with endoscopic inflammation in both IBD and represents the most reliable non-invasive biomarker of disease activity, whereas patient-reported outcomes are subject to bias. Methods We conducted a retrospective analysis of all patients with IBD receiving maintenance therapy with ADA at our tertiary center, with a particular focus on the outcome in those who experienced secondary LOR and underwent dose intensification. Data collected included ADA dosing regimen, trough levels, anti-drug antibodies, fecal calprotectin, and CDAI or Lichtiger scores at baseline and 3–6 months after dose intensification. Our primary hypothesis was that fecal calprotectin levels would decrease following intensification. Secondary objectives were to explore correlations between ADA trough levels and calprotectin levels. Statistical analyses used Wilcoxon and Spearman’s tests. Results 191 pat. on long-term ADA were included (UC: n=51; CD: n=141). Gender groups were balanced, 27 pat. received dual-targeted therapy, 52% received 80mg, 33% 40mg and 9% 60 mg ADA fortnightly. 56 patients (CD: n = 43; UC: n = 13) underwent dose intensification due to LOR. Most received an increase of 20mg (29%), 40mg (55%), or 80mg (11%). Following intensification, median calprotectin levels decreased significantly from 257µg/g (range 0–2100) to 58 µg/g (range 0–2100; p=0.0003). Median CDAI scores decreased from 36 (range 0–260) to 10 (range 0–180; p=0.05), and median CAI scores from 3 (range 0–260) to 2 (range 0–180; p=0.01). Median ADA trough levels increased from 6.8 to 12.6µg/ml after intensification (median dose 40 to 80mg fortnightly). Among 135 pat. who were not dose-intensified, no correlation was found between ADA trough levels and calprotectin (r = 0.001, p=0.99*). Conclusion Dose intensification of ADA in IBD patients with LOR is associated with a significant reduction in fecal calprotectin, suggesting improved anti-inflammatory activity. No correlation was observed between ADA trough levels and calprotectin. Our findings support dose intensification as a pragmatic and cost-effective strategy to recapture response in both, UC and CD, particularly as 40 and 80 mg formulations are often priced equivalently. Conflict of interest: Prof. Dr. Ochsenkuehn, Thomas: Scientific grant from Celltrion Waggershauser, Constanze: No conflict of interest Tillack-Schreiber, Cornelia: No conflict of interest Schnitzler, Fabian: No conflict of interest
Ochsenkuehn et al. (Thu,) studied this question.