(IBD) creating a whole new landscape for the disease.
Dr. Bharati Kochar
In 2007, IBD seemed to be primarily a disease of Caucasian and Jewish ancestry. While prevalence of IBD is still highest in the Western world, there is now increasing incidence, even accounting for detection bias, in people of all other ancestries globally. Incidence of IBD in children under the age of 18 years is also rising. Patients with IBD are living longer and, despite the notion that IBD is a disease primarily of younger adults, nearly one-third of Americans with IBD are 60 years and older.
“Adalimumab aids in Crohn’s disease” read the front page of the inaugural issue of GI & Hepatology News in January 2007. The article highlighted the GAIN study, which demonstrated that patients who lost response to infliximab responded to adalimumab, the second anti-tumor necrosis factor (TNF) agent approved for the treatment of Crohn’s disease and subsequently ulcerative colitis. Over the subsequent 15 years, the armamentarium of treatment options for Crohn’s disease and ulcerative colitis have rapidly proliferated: there are now four anti–tumor necrosis factor (TNF) agents, two anti-integrin agents, two anti-interleukin agents, two Janus kinase inhibitors and a sphingosine-1 receptor modulator approved for the treatment of IBD. Many more promising treatment options are in trials. Other mechanisms are under investigation as well, including antimicrobial therapies for ulcerative colitis and stem cell therapeutics for the treatment of refractory perianal fistulizing Crohn’s disease. Perhaps even more novel – dietary therapies are more rigorously under investigation.
“Ulcerative colitis guidelines endorse combined therapy” reads another headline from the inaugural GI & Hepatology News issue. The article discusses the European Crohn’s and Colitis Organisation’s consensus guideline that topical and systemic agents used together are superior to either used alone, referring specifically to mesalamine, both systemic and topical as well as the additional of topical corticosteroid to systemic mesalamine. Combination therapy has a completely new meaning in modern times. With the publication of the SONIC trial in 2010, combination therapy referred to an anti-TNF in combination with an immunomodulator for the ensuing decade. However, in this new era of IBD treatment, combination therapy could also mean a biologic with a small molecule or even combination biologics, for which there is an ongoing randomized controlled trial. On the topic of treatment strategies, one of the biggest shifts in the IBD treatment paradigm is the bottom-up versus top-down approach of treatment, with increasing evidence to suggest that early biologic initiation is more effective, especially in patients with Crohn’s disease. Therapeutic drug monitoring is mainstream. Treat-to-target strategies to achieve more stringent outcomes, such as biomarker, endoscopic and histologic normalization, especially in ulcerative colitis, have evolved to become the norm in 2022.
The combination of increased treatment options, decreased reliance on corticosteroids and stringent treatment strategies have resulted in improved outcomes: IBD-related hospitalizations, surgeries, and even mortality have declined since 2007. The growing recognition and focus on extra-intestinal manifestations, including fatigue, and the gut-brain axis are important steps to improving the overall quality of life of patients with IBD. Beyond treating the disease, we are now learning how to treat the patient. We will be developing personalized strategies to identify the right patient for the right treatment, including patient-level clinical and biologic markers. We need to identify those who are at risk for IBD to prevent the disease at a preclinical phase. Concomitantly, we must continue the quest to cure the disease!
Dr. Kochar is a gastroenterologist and inflammatory bowel disease specialist at Massachusetts General Hospital and a physician investigator in the clinical and translational epidemiology unit at The Mongan Institute, both in Boston. She has no relevant disclosures.
