Spotlight on ulcerative colitis

Recent guidelines, a meta-analysis, and a population-based cohort study all focused on patients with ulcerative colitis.

First, the American Gastroenterological Association (AGA) published recommendations on the management of patients with moderate to severe ulcerative colitis. The guidelines, developed by the AGA's Clinical Practice Guideline Committee, were published online on Jan. 13 by Gastroenterology.

Notable recommendations include the following:

• In adult outpatients with moderate to severe ulcerative colitis, use infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab rather than no treatment (strong recommendation, moderate-quality evidence).
• In adult outpatients with moderate to severe ulcerative colitis who are naive to biologic agents, use infliximab or vedolizumab, rather than adalimumab (conditional recommendation, moderate-quality evidence). However, patients (particularly those with less severe disease) who place a higher value on the convenience of self-administered subcutaneous injection compared to the relative efficacy of medications may reasonably choose adalimumab as an alternative, the guidelines said.
• In adult outpatients with moderate to severe ulcerative colitis in remission, use thiopurine monotherapy, rather than no treatment, for maintenance of remission (conditional recommendation, low-quality evidence).
• In adult outpatients with moderate to severe ulcerative colitis, do not use methotrexate monotherapy for induction or maintenance of remission (conditional recommendation, low-quality evidence).
• In hospitalized adult patients with acute severe ulcerative colitis, use an IV methylprednisolone dose equivalent to 40 to 60 mg/d rather than higher-dose IV corticosteroids (conditional recommendation, very low-quality evidence).
• Use infliximab or cyclosporine in hospitalized adult patients with acute severe ulcerative colitis refractory to IV corticosteroids (conditional recommendation, low-quality evidence).

Management of patients with moderate to severe ulcerative colitis was also the focus of an updated network meta-analysis, published online on Jan. 13 by Clinical Gastroenterology and Hepatology. Researchers compared the efficacy and safety of different first-line (biologic-naive patients) and second-line (patients with prior exposure to tumor necrosis factor [TNF] antagonists) pharmacotherapies to treat patients with moderately to severely active ulcerative colitis.

The systematic review included 15 randomized controlled trials of first-line agents and seven randomized controlled trials of second-line agents, as well as three additional studies from the researchers' previous analysis. Trials compared the medications with placebo or another active agent. Overall, the median of average age of patients was 41 years, and 60% were men. The median disease duration was 6.7 years, and 49% of patients had extensive colitis. A median of 40% of patients were treated with concomitant immunomodulators, and 51% were on corticosteroids at baseline. Researchers calculated odds ratios (ORs) and ranked agents using surface under the cumulative ranking (SUCRA) probabilities.

In biologic-naive patients, infliximab was ranked highest for induction of clinical remission (OR vs. placebo, 4.07 [95% CI, 2.67 to 6.21]; SUCRA, 0.95) and endoscopic improvement (SUCRA, 0.95). In patients with prior exposure to TNF antagonists, ustekinumab (SUCRA, 0.87) and tofacitinib (SUCRA, 0.87) were ranked highest for induction of clinical remission and were superior to vedolizumab and adalimumab. In maintenance trials, vedolizumab had the lowest risk of infections (SUCRA, 0.81), followed by ustekinumab (SUCRA, 0.63).

The authors noted the challenges of conducting network meta-analyses when trial designs are different and said that there are no thresholds for clinically meaningful differences between SUCRA values of different agents, among other limitations. “Pragmatic head-to-head trials in both biologic-naive and biologic-exposed patients are warranted to optimally inform relative positioning of newly available agents in clinical practice,” they wrote.

In the third and final study, researchers looked at the risks of colorectal cancer (CRC) mortality and incident CRC among patients with ulcerative colitis. They followed 96,447 patients with ulcerative colitis in Denmark (n=32,919) and Sweden (n=63,528) between Jan. 1, 1969, and Dec. 31, 2017, and compared them with individuals from the general population (n=949,207) who were matched for sex, age, birth year, and place of residence. Patients with ulcerative colitis were included if they had two or more records with a relevant diagnosis code in their country's patient register or if they had one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. Results were published Jan. 11 by The Lancet.

During follow-up, there were 1,336 incident CRCs in the ulcerative colitis cohort (1.29 per 1,000 person-years) and 9,544 incident CRCs in reference individuals (0.82 per 1,000 person-years; hazard ratio, 1.66 [95% CI, 1.57 to 1.76]). In the ulcerative colitis cohort, 639 patients died of CRC (0.55 per 1,000 person-years) compared with 4,451 reference individuals (0.38 per 1,000 person-years; hazard ratio, 1.59 [95% CI, 1.46 to 1.72]) during the same time period. The CRC stage distribution was less advanced in people with ulcerative colitis than in matched reference individuals (P<0.0001), and patients with ulcerative colitis and CRC remained at increased risk of CRC death after adjustment for tumor stage (hazard ratio, 1.54 [95% CI, 1.33 to 1.78]).

The hazard ratios for death from CRC and for CRC diagnosis decreased over time (both by calendar period of first ulcerative colitis diagnosis and by calendar year at the end of follow-up). During the last five years of follow-up in Sweden, the hazard ratios for CRC diagnosis and death from CRC for patients with ulcerative colitis decreased to 1.38 (95% CI, 1.20 to 1.60) and 1.25 (95% CI, 1.03 to 1.51), respectively.

Limitations of the study include an absence of data on smoking and other potential lifestyle risk factors and of data on mucosal or laboratory markers of disease activity, the authors noted. They added that the increased risk of death from CRC in patients with ulcerative colitis was mainly driven by younger ages of ulcerative colitis onset.

While the findings highlight the importance of surveillance colonoscopies, improvements in endoscopic detection of dysplasia and polyps alone are unlikely to explain the decrease in the hazard ratio of CRC in patients with ulcerative colitis, an accompanying comment noted. “To substantiate the premise that improved UC [ulcerative colitis] treatment has changed the natural history of CRC in this population, there has been a greater decline in CRC diagnosis in UC patients compared with the general population in the same period,” the editorialists wrote.