Faculty Bibliography

BACKGROUND & AIMS: Tofacitinib, an orally administered Janus kinase inhibitor, blocks signaling through gamma-chain-containing cytokines (interleukins 2, 4, 7, 9, 15, and 21). We performed a phase 2 trial to measure its efficacy in patients with moderate-to-severe active Crohn's disease. METHODS: Patients (N = 139; age, >/=18 y) with moderate-to-severe active Crohn's disease were assigned randomly to groups given 1 mg (n = 36), 5 mg (n = 34), or 15 mg (n = 35) tofacitinib or placebo (n = 34), twice daily for 4 weeks, at 48 centers in 12 countries. The primary end point was the proportion of clinical responders at week 4 (decrease from baseline in the Crohn's Disease Activity Index score of >/=70 points [Response-70]). Secondary end points included clinical remission (Crohn's Disease Activity Index score of <150 points) at week 4. RESULTS: A clinical response was observed in 36% (P = .467), 58% (P = .466), and 46% (P >/= .999) of patients given the 1-, 5-, and 15-mg doses of tofacitinib, compared with 47% of patients given placebo. Clinical remission was observed in 31% (P = .417), 24% (P = .776), and 14% (P = .540) of patients given the 1-, 5-, and 15-mg doses of tofacitinib, compared with 21% of patients given placebo. The 15-mg dose of tofacitinib reduced levels of C-reactive protein and fecal calprotectin from baseline. Adverse and serious adverse events were similar among groups. Dose-dependent increases in low- and high-density lipoprotein cholesterol were observed in patients given the 5- or 15-mg doses of tofacitinib. CONCLUSIONS: There were no significant differences in the percentage of patients with moderate-to-severe active Crohn's disease who achieved clinical responses (Response-70) or clinical remission after 4 weeks' administration of tofacitinib (1, 5, or 15 mg) or placebo twice daily. However, a large percentage of patients given placebo achieved Response-70 or remission. Reductions in C-reactive protein and fecal calprotectin levels among patients given the 15-mg dose of tofacitinib indicate its biologic activity. ClinicalTrials.gov number: NCT00615199.

As the global population ages, the number of older people (>/=65 years) living with IBD is expected to increase. IBD therapeutics have advanced considerably over the past few decades with the introduction of multiple steroid-sparing agents as well as numerous clinical trials that have tested new therapeutic targets. However, the current paradigms for IBD management might not be directly translatable to older patients with IBD. Age-related factors such as immunodeficiency relative to younger patients, comorbidity, polypharmacy and diminished physical reserve directly or indirectly affect the natural history of their disease. This Review highlights how these age-associated variables can affect older patients with IBD and also illustrates the multiple gaps in our current knowledge of IBD in the elderly.

There has been limited research examining the risks, benefits, and use of common endoscopic procedures in the elderly. Furthermore, gastroenterology training programs do not routinely incorporate elderly concerns when dealing with common gastrointestinal issues. There exists a broad array of endoscopic procedures with varying inherent risks that must be weighed with each elderly patient in mind. This article discusses the benefits and drawbacks of the most common procedures and indications for endoscopy including upper endoscopy, colonoscopy, endoscopic retrograde cholangiopancreatography, endoscopic ultrasound, percutaneous endoscopic gastrostomy, and deep enteroscopy.