Ulcerative colitis - Emerging treatments

Filgotinib

Filgotinib, a selective Janus kinase (JAK) inhibitor, has been approved by the European Medicines Agency (EMA) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biological agent. Approval was based on data from a phase 2b/3 study comparing filgotinib with placebo in patients with moderately to severely active UC. During the induction at week 10, more patients receiving filgotinib achieved clinical remission than those receiving placebo. At week 58, 37.2% in the filgotinib group had clinical remission compared with 11.2% in the placebo group.[102] The UK National Institute for Health and Care Excellence (NICE) recommends filgotinib as an option for adults with moderately to severely active UC.[103] Filgotinib is not available in the US. However, the American Gastroenterological Association (AGA) suggests the use of filgotinib in moderate-to-severe UC over no treatment, and suggests using an intermediate-efficacy drug such as filgotinib in patients who are naive to advanced therapies or who have previously been exposed to one or more advanced therapies, particularly tumour necrosis factor (TNF)-α antagonists.[45]

Leukocytapheresis

Selective apheresis for treatment of inflammatory bowel disease, in particular UC, has been used in Japan and some European countries for several years. Unlike conventional pharmacological treatments, selective apheresis, where a proportion of leukocytes are mechanically removed from the circulatory system, may be associated with a relatively low rate of adverse events.[104][105] Multiple studies have suggested that selective apheresis in combination with conventional pharmacotherapy may improve response and remission rates, promote a corticosteroid-sparing effect, and maintain clinical remission of UC.[104][105][106][107][108][109]

Antibiotics

One Cochrane review found no difference between adding antibiotics or placebo to standard therapies in patients with UC to achieve clinical remission. However, there is evidence that there may be more patients achieving clinical remission or experiencing some improvement of UC symptoms with antibiotics compared with placebo at 12 months. The review found that there may be no difference in serious adverse events (or withdrawals due to adverse events) between antibiotics and placebo.[110] [ ] Both the AGA and British Society of Gastroenterology (BSG) do not support adjunctive antibiotics in hospitalised patients with acute moderate-to-severe UC unless there is evidence of infection.[26][45]

Budesonide and prednisolone enemas

Budesonide and prednisolone are available as enemas and have fewer systemic adverse effects than oral corticosteroids. Budesonide rectal foam appears to be well tolerated and significantly more efficacious than placebo in inducing remission in patients with mild-to-moderate distal UC.[111][112]

Probiotics

One Cochrane systematic review reported no statistically significant difference between the efficacy of probiotics and mesalazine, and probiotics and placebo, for maintenance of remission in UC.[113] [ ] Conventional therapy when combined with a probiotic does not improve remission rates in patients with mild-to-moderate UC.[7] Studies evaluating probiotics for UC are limited by trial design and use of different probiotics with variable bacterial contents.[113][114][115][116][117] [ ] Probiotics should not be routinely recommended for inducing or maintaining remission in UC. Both the American Journal of Gastroenterology (AJG) and BSG do not suggest the routine use of probiotics for induction or maintenance of remission in patients with UC.[23][23]

Beclometasone

Beclometasone dipropionate is a second generation corticosteroid. The American College of Gastroenterology (ACG) suggests beclomethasone suppositories for patients with mildly to moderately active proctitis not responsive to topical 5-aminosalicylate (5-ASA) over no treatment.[23] It is conditionally recommended by the BSG for induction of remission in patients with UC where 5-ASA therapy fails or is not tolerated, or in those who wish to avoid stronger systemic corticosteroids.[26] In a double-blind, randomised, parallel-group study of patients with active mild-to-moderate UC, oral prolonged-release beclometasone dipropionate was non-inferior to prednisolone in reducing disease activity, with a similar safety profile.[118] Meta-analysis of seven randomised controlled trials showed no significant differences between beclometasone and mesalazine in inducing and maintaining remission, with comparable safety profiles.[119] The place of second-generation corticosteroids in combination with aminosalicylate therapy is unclear. Oral and topical beclometasone dipropionate are not available in the US.

Faecal microbiota transplantation (FMT)

One Cochrane review concluded that, while faecal microbiota transplantation may increase the likelihood of clinical remission in UC, the evidence is too uncertain to recommend it.[120] [ ] The ACG notes that although FMT has shown some promising data in the treatment of UC, there is not enough to show significant corticosteroid-sparing effects, and the variability within the studies do not allow for FMT to be a recommended treatment option. Further research is required.[23][121]