Crohn disease - Emerging treatments

Mirikizumab

Mirikizumab is an interleukin (IL-23) antagonist. One global phase 3, multicenter, randomized, double-blind trial (VIVID-1) studied mirikizumab in patients with moderately to severely active CD and found that it was safe and effective as induction and maintenance treatment in patients who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic treatment.[260] Both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved mirikizumab for the treatment of moderately to severely active Crohn disease (CD) in adults.

Guselkumab

Guselkumab, another IL-23 antagonist, is approved by the FDA and the EMA for the treatment of moderately to severely active CD. The approval is based on the results of the phase 2/3 GALAXI trials which evaluated intravenous induction and subcutaneous maintenance of guselkumab versus placebo, and the phase 3 GRAVITI trial which evaluated subcutaneous induction and maintenance of guselkumab versus placebo.[261][262][263] Both trials demonstrated promising clinical and endoscopic outcomes when compared with placebo, suggesting that both intravenous and subcutaneous administration options can be offered to patients with moderately to severely active CD.[264][265]

Sphingosine 1-phosphate (S1P) receptor modulators

S1P receptor modulators (e.g., ozanimod, etrasimod) have been found to be effective in inflammatory bowel disease for inducing clinical and endoscopic remission and, in some cases, histologic response.[266] In one phase 2 uncontrolled study of patients with moderately to severely active CD, clinical improvements were reported within 12 weeks of initiating ozanimod, an oral agent selectively targeting S1P receptor subtypes 1 and 5.[267] A phase 3 study is ongoing.[268] Ozanimod and etrasimod are currently approved for the management of UC but not CD.

Autologous hematopoietic stem cell transplantation

An analysis of pooled data from one randomized clinical trial suggested that hematopoietic stem cell transplantation (HSCT) may be of some clinical and endoscopic benefit in patients with refractory CD not amenable to surgery.[269] However, treatment is associated with significant toxicity. One prospective study concluded that, while HSCT may be feasible in patients with refractory CD, extraordinary supportive measures are required.[270] A multicenter, randomized controlled trial is ongoing.[271] Mesenchymal stem cells have also been trailed as a treatment for perianal fistulae with promising results.[272][273]

Antituberculous therapy

Clinical and pathologic observations have suggested a possible link between CD and atypical mycobacteria. One Cochrane review found that antituberculous therapy may be beneficial for preventing relapse of CD in patients with quiescent disease. However, the result is uncertain and further studies are required to provide higher-quality evidence.[274]

CD exclusion diet

One small pilot study reported that CD exclusion diet, with or without partial enteral nutrition (PEN), was effective for the induction and maintenance of remission in adults with mild or moderate, biologic-naive CD.[275] Since then, one meta-analysis of 27 studies has revealed potential benefit with PEN for induction and maintenance of remission in CD; however, certainty of evidence remains low.[276] The CD exclusion diet is high in protein and low in heme, gluten, animal fat, and additives. The diet contains pectin, resistant starch, and fiber. Further large randomized trials are needed.