Asian Landscape of Ulcerative Colitis and Inflammatory Bowel Disease
Ulcerative colitis (UC), being the primary type of inflammatory bowel disease (IBD) globally [1] is an inflammatory condition of the colon characterised by diffuse friability and superficial erosions on the colonic wall and associated bleeding. Typical presentation of UC begins in the rectum, extending to the proximal area. In Asia, a 2016 study [2] concluded that around 1 per 100,000 have UC, with the total incidence of IBD ranging from 0.5 to 3 per 100,000 people across nations in Asia.
Introduction of Etrasimod for Ulcerative Colitis
Pfizer, the company that developed etrasimod, announced [3] in December 2022 that the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have accepted its request for review of this new medication for ulcerative colitis. Etrasimod is an oral, once-daily, selective, sphingosine 1-phosphate receptor modulator for the treatment of immune-mediated diseases, such as UC.
Clinical Studies of Etrasimod: Efficacy in Ulcerative Colitis
In March 2023, The Lancet published an article [4] on etrasimod as induction and maintenance therapy for ulcerative colitis with two randomised, double-blind, placebo-controlled, phase 3 studies (coded ELEVATE UC 52 & ELEVATE UC 12) that brought exciting result to the community.
Both studies enrolled adults with active moderate-to-severe ulcerative colitis with either inadequate, loss of response or intolerance to at least one approved ulcerative colitis therapy. They were randomly assigned (2:1) to once-daily oral etrasimod 2 mg or placebo. Patients in ELEVATE UC 52 were enrolled from 315 centres in 40 countries; patients in ELEVATE UC 12 were enrolled from 407 centres in 37 countries. ELEVATE UC 52 comprised a 12-week induction period followed by a 40-week maintenance period with a treat-through design. ELEVATE UC 12 independently assessed induction at week 12. The primary efficacy endpoints were the proportion of patients with clinical remission at weeks 12 and 52 in ELEVATE UC 52 and week 12 in ELEVATE UC 12.
After the clinical data was collected for analysis, the full set of ELEVATE UC 52 comprised 289 patients assigned to etrasimod and 144 to placebo. In ELEVATE UC 12, 238 patients were assigned to etrasimod and 116 to placebo. In ELEVATE UC 52, a significantly greater proportion of patients in the etrasimod group achieved clinical remission compared with patients in the placebo group at completion of the 12-week induction period (74 [27%] of 274 patients vs 10 [7%] of 135 patients; p<0·0001) and at week 52 (88 [32%] of 274 patients vs 9 [7%] of 135 patients; p<0·0001).
Figure 1 Coprimary endpoints of clinical remission at week 12 and at week 52 (A), key secondary and additional prespecified secondary endpoints at week 12 and week 52 (B), and key secondary and additional prespecified endpoints of sustained remission and corticosteroid-free remission at week 52 in ELEVATE UC 52 (C)
In ELEVATE UC 12, 55 (25%) of 222 patients in the etrasimod group had clinical remission compared with 17 (15%) of 112 patients in the placebo group at the end of the 12-week induction period (p=0·026).
Figure 2 The primary endpoint of clinical remission at week 12 (A) and key secondary and additional prespecified secondary endpoints at week 12 (B) in ELEVATE UC 12
Clinical Studies of Etrasimod: Safety Profile
Adverse events were reported in 206 (71%) of 289 patients in the etrasimod group and 81 (56%) of 144 patients in the placebo group in ELEVATE UC 52 and 112 (47%) of 238 patients in the etrasimod group and 54 (47%) of 116 patients in the placebo group in ELEVATE UC 12. The most frequently reported adverse events (in ≥1% of patients) included anaemia, headache, and worsening of ulcerative colitis or ulcerative colitis flare. In both studies, overall infections, serious infections, and opportunistic infections (ie, tuberculosis and cytomegalovirus infection) were similar between the treatment groups. No deaths or malignancies were reported.
Final Takeaway
Despite recognizing UC for decades, we have yet to come out with an effective and low-risk treatment plan to control the condition. UC 52 and UC 12 studies have both shined light into the clinical situation and brought hope for current patients suffering from UC. Once approved, we could see more clinical data coming in and formally assess its efficacy on a large scale.
Reference:
- Lynch WD, Hsu R. Ulcerative Colitis [Internet]. Nih.gov. StatPearls Publishing; 2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459282/
- Ng SC. Emerging Trends of Inflammatory Bowel Disease in Asia. Gastroenterology & hepatology [Internet]. 2016 [cited 2023 May 17];12(3):193–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872848/#:~:text=In%20addition%2C%20we%20found%20that
- Pfizer Announces FDA and EMA Acceptance of Etrasimod Regulatory Submissions for Ulcerative Colitis | Pfizer [Internet]. www.pfizer.com. 2022. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-fda-and-ema-acceptance-etrasimod
- Sandborn WJ, Vermeire S, Peyrin-Biroulet L, Dubinsky MC, Panes J, Yarur A, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. The Lancet [Internet]. 2023 Mar 2 [cited 2023 Mar 3]; Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00061-2/fulltext
