ABSTRACT
Introduction: Adalimumab (ADA) intensification is recommended for inadequate or loss of response in inflammatory bowel disease (IBD) patients. A new presentation of ADA 80mg administered every other week (eow) has been approved as an alternative to ADA 40mg every week (ew). Data regarding impact of ADA 80mg eow in clinical practice is still scarce. The aim of this study was to assess long-term durability, safety and cost-effectiveness of treatment with ADA 80mg eow in patients with IBD. Aims & Methods: The aim of this study was to assess long-term durability, safety and cost-effectiveness of treatment with ADA 80mg eow in patients with IBD. A retrospective cohort study in a tertiary hospital that included all IBD patients under intensified maintenance therapy with ADA 80mg eow was performed. Durability was calculated considering the time from the first dose to treatment withdrawn or to the end of follow-up. Biological remission (BR) was defined as CR together with fecal calprotectin (FC) <250 μg/g and C-reactive protein (CRP) <5mg/dl. A descriptive analysis was carried out and the data are presented as percentage, median and interquartile range (IQR). A Kaplan-Meier analysis was used to assess durability, multivariate step-by-step analysis using Cox model to investigate factors potentially associated with treatment withdrawn and Wilcoxon signed rank test to compare differences in FC, RCP and ADA levels before and after intensification. Economic impact of ADA 80 eow was estimated considering current price of both ADA 40mg and ADA 80mg pens at our centre: we estimated the cost of 2 ADA 40mg pens for each ADA 80mg used in our patients Results: Eighty-seven patients (72 CD and 15 CU) were included;median age 50 (IQR 40-60), 58% male;median duration of the disease before ADA of 14 years (IQR 7-22);27% were active smokers. Among CD patients, 47% had ileal disease, 14% colonic and 23% ileocolonic. The inflammatory behavior was the most frequent (53%) and 32% had perianal disease. In UC, 47% had extensive colitis. 61 patients (71%) were bio-naïve and 44 (51%) received immunosuppressants at baseline. At the time of escalation, 57 patients (66%) were symptomatic. After intensification, 75 (86%) patients (CD 61 [85%] and UC 14 [93%]) achieved CR and 69 (79.3%) BR. The changes in the levels of FC (median: 176 vs 70), CRP (median: 3.8 vs 1.7) and ADA (4.17 vs 8.53) were significant (p <0.001). 24 patients (28%) discontinued treatment after a median of 6.5 (IQR 4.5- 10.5) months due to: 11 no clinical response (46%), 5 loss of response (21%), 3 adverse events (12%) (psoriasis), 4 endoscopic progression (17%) and 1 fear of COVID-19 (4%). 63 patients (72%) remained under treatment and in CR (median follow-up 19 months, IQR 13-25) and with a median ADA levels of 10.68 mg/l (IQR 7.67-15). 83 patients (95%) reported being satisfied with the administration of ADA 80 mg eow. Use of ADA 80 eow regimen saved 356100€ in patients who maintained treatment. In the multivariate analysis, being in CR when intensifying reduced the risk of treatment discontinuation by 83% (HR 0.17, 95% CI 0.02-1.26;p = 0.02), having reached BR by 96.8% (HR 0.03, 95% CI 0.01-0.09;p <0.001) and having ADA levels ≥5 mg/l after intensification by 48% (HR 0.52, 95% CI 0.3-0.92;p = 0.02). Conclusion: ADA intensification to 80mg eow in IBD patients is safe, effective and may reduce costs in real life clinical practice. Early intensification, even in CR, may enhance ADA treatment durability.