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 UC who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic 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.[98] Filgotinib is not available in the US as yet.

Biosimilars

Several biologic therapies have reached, or will soon reach, patent expiry. Biosimilars are drugs designed to be highly similar, in chemical and biologic terms, to existing biologic medicines. Biosimilars can deliver cost savings without significant differences in efficacy and safety.[99][100]

Leukocytapheresis

Selective apheresis for treatment of inflammatory bowel disease (IBD), in particular UC, has been used in Japan and some European countries for several years. Unlike conventional pharmacologic 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.[101][102] 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.[101][102][103][104][105][106]

Etrolizumab

Etrolizumab is a humanized monoclonal antibody against alpha 4 beta 7 integrin and alpha E beta 7 integrin. One systematic review found that etrolizumab may be an effective induction therapy for some patients with moderate-to-severe UC who have failed conventional therapy.[107] [ ] Phase 3 trials of etrolizumab are ongoing.[108][109][110]

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.[111] [ ]

Budesonide and prednisone enemas

Budesonide and prednisone 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.[112][113]

Probiotics

One Cochrane systematic review reported no statistically significant difference between the efficacy of probiotics and mesalamine, and probiotics and placebo, for maintenance of remission in UC.[114] [ ] 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.[114][115][116][117][118] [ ] Probiotics should not be routinely recommended for inducing or maintaining remission in UC.

Beclomethasone

In a double-blind, randomized, parallel-group study of patients with active mild-to-moderate UC, oral prolonged-release beclomethasone dipropionate was noninferior to prednisone in reducing disease activity, with a similar safety profile.[119] Meta-analysis of seven RCTs showed no significant differences between beclomethasone and mesalamine in inducing and maintaining remission, with comparable safety profiles.[120] The place of second-generation corticosteroids in combination with aminosalicylate therapy is unclear.

Fecal microbiota transplantation

One Cochrane review concluded that, while fecal microbiota transplantation may increase the likelihood of clinical remission in UC, the evidence is too uncertain to recommend it.[121] [ ] Further research is required.[122]