Ulcerative Colitis: 5 Things to Know

Stephen B. Hanauer, MD

Disclosures

January 23, 2019

Recent years have seen both progress and setbacks in the management of ulcerative colitis (UC), which, along with Crohn disease (CD), represents one of the two major types of inflammatory bowel disease (IBD). The prevalence of UC has increased around the world, and patients are increasingly vulnerable to infection and other serious complications. Conversely, great strides have been made in the therapeutic treatment of UC and the surveillance of life-threatening diseases associated with it. This article highlights five key areas that practitioners treating patients with UC need to know.

1. IBD Has Gone Global

Once considered "Western" diseases, the incidence and prevalence of both UC and CD have been on the rise in the East and in South America.[1] In most environs, the increased incidence of UC has preceded that of CD by a decade, although tuberculosis remains a major confounder in the diagnosis of CD.[2]

The increasing prevalence of IBD was initially recognized in those newly arrived in the West, in both Europe and North America, where first-generation immigrants assumed a similar incidence as in that of the new country and far greater than that of their country of origin.[3] The rising incidence of UC has also been reported in Japan and South Korea, and subsequently in India and China.[1,2]

The epidemiologic factors in the West and East overlap but are primarily attributable to the environment rather than to genetics.[2,4] Although over 200 gene mutations have been associated with IBD, the spectrum of mutations is different and does not account for the similar phenotypic presentations in disparate environments.

A far more likely cause is the relationship to diet and hygiene and how they collectively influence the gut microbiome.[5] Prolonged breast-feeding remains a protective factor for IBD, and perhaps the most intriguing epidemiologic commonality is the risk of developing UC after cessation of cigarette smoking.[6]

2. Medical Options for Moderate-to-Severe Disease Are Expanding

The American Gastroenterological Association (AGA) has developed a "pathway" (as opposed to a guideline) for the treatment of moderate to severe UC.[7] The AGA notes that, in the absence of head-to-head comparative effectiveness trials, options for moderate to severe disease activity include a short course of corticosteroids followed by thiopurine maintenance, antitumor necrosis factor (anti-TNF) biologics with or without an immunosuppressive agent, or the novel anti-integrin drug vedolizumab with or without an immunosuppressive agent. Most recently, tofacitinib, an oral Janus kinase inhibitor, has been approved for the treatment of moderate-to-severe UC[8] and will certainly be included in the next iteration of the pathway and subsequent guidelines.

As of January 2019, there will be three originator TNF inhibitors (infliximab, adalimumab, and golimumab) approved to treat moderate-to-severe UC, as well as two infliximab biosimilars.[9] In pivotal phase 3 studies enrolling patients who had failed conventional therapies (with approximately 40% failing immunosuppressive therapy), post hoc analyses did not demonstrate differences in the outcomes of those receiving concomitant thiopurines.[10,11,12] However, in a prospective trial with infliximab, the addition of azathioprine did provide benefits over infliximab monotherapy.[13] Similarly, a post hoc analysis of the phase 3 trial leading to approval of vedolizumab also did not demonstrate a benefit to combination therapy for patients who were not responding to a thiopurine.[14] While prospective, randomized controlled trials would be necessary to demonstrate a benefit of combination therapy with vedolizumab and an immunomodulator, the current absence of evidence in favor of combination therapy and the otherwise favorable safety profile for vedolizumab make monotherapy more appealing. Recent "real-world" studies have expanded on the vedolizumab pivotal trials and, for the most part, demonstrate long-term efficacy and safety of vedolizumab (mono- or combination therapy), particularly for patients not previously exposed to anti-TNF biologics.[15,16,17]

Tofacitinib provides an oral therapeutic option for the treatment of moderate-to-severe UC but should not be used in combination with other immunosuppressive agents. Similar to vedolizumab, tofacitinib was more effective in biologic-naïve patients.[18] Tofacitinib is associated with a risk for infection and possibly neoplasia (eg, lymphoma) and herpes zoster.[19]

In the absence of comparative effectiveness studies, recent network meta-analyses have suggested that the preference may be for using TNF inhibitors and vedolizumab as first-line biologics, with tofacitinib as second-line therapy for patients who have been previously exposed to TNF inhibitors.[20,21]

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