AST-120 (spherical carbon adsorbent) in the treatment of perianal fistulae in mild-to-moderate Crohn's disease: FHAST-1, a phase 3, multicenter, placebo-controlled study.
BACKGROUND
AST-120 (spherical carbon adsorbent) was previously reported to be effective for perianal fistula healing in Japanese patients with mild-to-moderate Crohn's disease.


METHODS
To evaluate the efficacy and safety of AST-120 in a Western population, a phase 3, multicenter, randomized, double-blind, placebo-controlled, study (FHAST-1) was conducted in adult patients with at least 1 draining perianal fistula and a Crohn's disease activity index <400. Patients received either AST-120 or matching placebo at a dose of 2 g 3 times daily for 8 weeks. The primary endpoint was the proportion of patients with treatment success, defined as a 50% reduction in the number of draining fistulae, at both weeks 4 and 8. A multivariate model was generated to assess covariates for treatment success among baseline variables.


RESULTS
Two hundred forty-nine patients were randomized (AST-120; n = 122; placebo, n = 127). The proportions of patients achieving the primary endpoint were no different between treatment groups (13.9% versus 16.5%, P = 0.6). No differences in fistula response were noted at week 4 (23.0% versus 25.2%, P = 0.77) or week 8 (27.0 versus 34.6%, P = 0.22). Serum C-reactive protein concentrations >0.6 mg/dL and Crohn's disease activity index scores >151 at baseline were associated with a reduced likelihood of treatment success (odds ratio, 0.40; confidence interval, 0.19-0.87; P = 0.02; and odds ratio, 0.45; confidence interval, 0.21-0.97; P = 0.04, respectively).


CONCLUSIONS
In this largest placebo-controlled trial to date to evaluate the impact of a therapeutic agent on perianal fistulae in Crohn's disease, the efficacy of AST-120 could not be confirmed. An inverse relationship was observed between both inflammatory and clinical disease activity and fistula response.
*Medical University of Vienna, Vienna, Austria; †Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; ‡Northwestern University Feinberg School of Medicine, Chicago, Illinois; §Medstar Health Research Institute, Hyattsville, Maryland; ‖Georgetown University School of Medicine, Washington, District of Columbia; and ¶Ocera Therapeutics, San Diego, California.
Walter
W
Reinisch
Simon
S
Travis
Stephen
S
Hanauer
Hong
H
Wang
Nawar
N
Shara
M Scott
MS
Harris
D000293:Adolescent; D000328:Adult; D000368:Aged; D002244:Carbon / Q000627:therapeutic use*; D003424:Crohn Disease / Q000150:complications* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010087:Oxides / Q000627:therapeutic use*; D011446:Prospective Studies; D012003:Rectal Fistula / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
D005765:Gastrointestinal Agents; D010087:Oxides; D002244:Carbon; C040896:AST 120