Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial

Amon Asgharpour, Jianfeng Cheng, Stephen J Bickston VCUHS Center for Inflammatory Bowel Disease, Virginia Commonwealth University Health Center, Richmond, VA, USA Abstract: The advent of anti-tumor necrosis factor (TNF) therapies revolutionized the treatment of inflammatory bowel disease. Adalimumab is a subcutaneous anti-TNF agent indicated for use in patients with moderate-to-severe Crohn's disease and those with moderate-to-severe ulcerative colitis. In both diseases, it can be used for both induction of remission and for maintenance of remission. This review focuses on its use in Crohn's disease as described in the EXTEND (Extend the Safety and Efficacy of Adalimumab through Endoscopic Healing) trial. Several clinical trials using traditional instruments to measure clinical response have had endoscopic substudies looking for endoscopic healing. The EXTEND trial is the first to use mucosal healing on endoscopy as a primary endpoint for patients with moderate-to-severe Crohn's disease and baseline ulcerative disease treated with continuous adalimumab. In this well designed trial, the primary endpoint was narrowly missed, but the secondary endpoints further the notion that mucosal healing should be a more mainstream measure of drug efficacy. How this will translate from clinical trials to the clinic is not yet clear, but identifying noninvasive markers for mucosal healing, and understanding the implications of mucosal healing for safety, resource utilization, and quality of life are all worthy targets for further study. The aim of this review is to understand the role of mucosal healing, safety profile, and efficacy in patients treated with anti-TNF therapy, with particular attention to adalimumab and the EXTEND trial. Keywords: Crohn's disease, tumor necrosis factor, adalimumab, clinical trials, inflammatory bowel diseas

Systematic review: societal cost of illness of inflammatory bowel disease is increasing due to biologics and varies between continents

Background: Knowledge of the cost of illness of inflammatory bowel disease (IBD) is essential for health policy makers worldwide. Aim: To assess the cost of illness of IBD from the societal perspective taking into account time trends and geographical differences. Methods: A systematic review of all population-based studies on cost of illness of IBD published in Embase, Medline, Web of Science and Google Scholar. Methodology of included studies was assessed and costs were adjusted to 2018 US dollars. Results: Study methodologies differed considerably, with large differences in perspective, valuation method and population. For prevalent Crohn's disease (CD) cases in the last ten years annual healthcare costs were in Asia $4417 (range$1230-$31 161); Europe$12 439 ($7694-$15 807) and North America $17 495 ($14 454-$20 535). For ulcerative colitis (UC), these were$1606 ($309-$14 572), $7224 ($3228-$9779) and$13 559 ($13 559-$13 559). The main cost driver was medication, the cost of which increased considerably between 1985 and 2018, while outpatient and inpatient costs remained stable. IBD had a negative impact on work productivity. Annual costs of absenteeism for CD and UC were in Asia (with presenteeism) $5638 ($5638-$5638) and$4828 ($4828-$4828); Europe $2660 ($641-$5277) and$2394 ($651-$5992); North America $752 ($307-$1303) and$1443 ($85-$2350). Conclusion: IBD societal cost of illness is increasing, driven by growing costs of medication, and varies considerably between continents. While biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, these costs have not declined