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

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.

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

“…A previous study showed similar findings with a 44.4% steroid-free rate during anti-TNF-α (IFX) treatment 19. Mucosal healing is the current goal of treating CD patients to reduce the need for hospitalizations and surgery 7. In our study, the mucosal healing rate was 25% after 6-12 months treatment, which is similar to the EXTEND trial of 27% at week 12 4.…”

“…The safety and efficacy of ADA for CD have been extensively tested in Western countries, but much less so in Asian countries 3,6,7,8,9,10,11. In Japan, ADA was approved for CD treatment since 2010.…”

“…From the EXTEND trial, adverse events and serious adverse events were noted in 42.2% and 6.3% of the patients 7. Serious infections developed during IFX treatment for CD was noted in 4.9% of the patients 19.…”

The rescue effect of adalimumab in the treatment of refractory pediatric panuveitis complicated with steroid-induced glaucoma

“…[ 3 10 11 12 ] Adalimumab is a recombinant human IgG1 monoclonal antibody to TNFα that also affects receptor-bound TNFα. It is approved for use in children with enthesitis-related arthritis,[ 13 ] severe plaque psoriasis,[ 14 ] severe Crohn's disease,[ 15 ] and active JIA. [ 14 ] It has also been used in the patients with intraocular inflammation as a rescue therapy, and been shown to be effective in controlling uveitis in a pediatric group.…”

Differences in the public medical insurance systems for inflammatory bowel disease treatment in Asian countries

“…In contrast, the percentage of IBD patients taking biologics is lowest in India, where the coverage rate by public health insurance is low and IBD patients have to pay for most of their medical expenses. As biologics have been proven to improve the clinical and mucosal status of IBD patients, 7 determining whether the difference will affect the outcomes (such as operation rate, admission rate, or even mortality rate) needs a longer period of follow-up.…”