{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:37:58Z","timestamp":1791466678266,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RedHill Biopharma Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn\u2019s disease. A double-blind multicenter study of adults with active Crohn\u2019s disease, (i.e., Crohn\u2019s Disease Activity Index [CDAI] 220\u2013450 plus C-reactive protein \u2265 1.0 mg\/dL, fecal calprotectin (FCP) &gt;162.9 \u00b5g\/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn\u2019s disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, and clofazimine 10 mg per capsule) (n = 166), resulting in clarithromycin 950 mg\/day, rifabutin 450 mg\/day, and clofazimine 100 mg\/day, or placebo (n = 165) for up to 52 weeks. A greater proportion of RHB-104 versus placebo-treated patients met the primary endpoint\u2014remission (i.e., CDAI &lt; 150)\u2014at week 26 (36.7% [61\/166] vs. 22.4% [37\/165], respectively; 95% CI for difference: 4.6, 24.0, p = 0.0048; chi-square test). Clinical response (reduction of CDAI by \u2265100 points from baseline) at week 26 (first secondary endpoint) was also higher among the patients treated with RHB-104 (73\/166 [44.0%]) compared with placebo (50\/165 [30.3%]; 95% CI for difference: 3.4, 24.0, p = 0.0116), and it remained higher at week 52 among the patients treated with RHB-104 (59\/166 [35.5%] vs. (35\/165 [21.2%] for placebo; 95% CI for difference: 4.7, 23.9, p = 0.0042). A statistically significantly greater decline in FCP (another prospective efficacy endpoint) was also observed in RHB-104-treated patients, compared with placebo, at weeks 12, 26, and 52. The rates of serious adverse events were similar between groups (RHB-104: 18.7%; placebo: 18.8%). No patient died during the study. Antimicrobial therapy directed against MAP resulted in significantly greater improvement in clinical and laboratory (FCP) measures of active Crohn\u2019s disease.<\/jats:p>","DOI":"10.3390\/antibiotics13080694","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T08:40:04Z","timestamp":1721896804000},"page":"694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-8317","authenticated-orcid":false,"given":"David Y.","family":"Graham","sequence":"first","affiliation":[{"name":"Departments of Medicine, Molecular Virology, and Microbiology, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-4527","authenticated-orcid":false,"given":"Saleh A.","family":"Naser","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-4698","authenticated-orcid":false,"given":"Thomas","family":"Borody","sequence":"additional","affiliation":[{"name":"Center for Digestive Diseases, Sydney 2046, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Hebzda","sequence":"additional","affiliation":[{"name":"Specjalistyczne Centrum Medyczne Unimedica, 31-271 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Sarles","sequence":"additional","affiliation":[{"name":"Digestive Health Associates of Texas (DHAT) Research Institute, Garland, TX 75044, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Levenson","sequence":"additional","affiliation":[{"name":"Digestive Care Associates, Inc., San Carlos, CA 94070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hardi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, George Washington University Medical School, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-4211","authenticated-orcid":false,"given":"Tomasz","family":"Ar\u0142ukowicz","sequence":"additional","affiliation":[{"name":"Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Svorcan","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Zvezdara University Medical Center, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Fathi","sequence":"additional","affiliation":[{"name":"RedHill Biopharma, Ltd., Tel Aviv 6473921, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Bibliowicz","sequence":"additional","affiliation":[{"name":"RedHill Biopharma, Ltd., Tel Aviv 6473921, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Anderson","sequence":"additional","affiliation":[{"name":"RedHill Biopharma, Ltd., Tel Aviv 6473921, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"McLean","sequence":"additional","affiliation":[{"name":"RedHill Biopharma, Ltd., Tel Aviv 6473921, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Fehrmann","sequence":"additional","affiliation":[{"name":"CEEF Solutions, Pointe-Claire, QC H9S 4L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Scott","family":"Harris","sequence":"additional","affiliation":[{"name":"Middleburg Consultants, Takoma Park, MD 20912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Syneos Health, Morrisville, NC 27560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira N.","family":"Kalfus","sequence":"additional","affiliation":[{"name":"M2g Consulting, Inc., New York, NY 10024, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/ajg.2015.233","article-title":"Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target","volume":"110","author":"Sandborn","year":"2015","journal-title":"Am. 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