Controlled trial of antimycobacterial therapy in Crohn's disease

Digestive Diseases and Sciences - Tập 36 - Trang 449-453 - 1991
N. H. Afdhal1, A. Long1, J. Lennon1, J. Crowe1, D. P. O'Donoghue1
1Departments of Gastroenterology, Dublin, Ireland

Tóm tắt

In order to study the effect of clofazimine, a powerful antimycobacterial and antiinflammatory agent, 49 patients with active Crohn's disease were randomized to either corticosteroids plus clofazimine 100 mg daily (N=25) or to steroids and matching placebo (N=24). A total of 28 patients (58%) went into disease remission (clofazimine 16, placebo 12;P=NS) with a fall in disease activity score from 10.5±4.4 to 3.3±3.5. Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study (clofazimine 12, placebo 6;P=NS). Side effects were minor and consisted of skin rash and increased pigmentation. Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn's disease but may have a role in either disease maintenance or combination chemotherapy.

Tài liệu tham khảo

James SP, Strober W, Quinn TC, Danovitch SH: Crohn's disease; new concepts of pathogenesis and current approaches to treatment. Dig Dis Sci 32:1297–1310, 1987 Burnham WR, Lennard-Jones JE, Stanford TL, Bird RG: Mycobacteria as a possible cause of inflammatory bowel disease. Lancet 2:693–696, 1978 Donnelly BJ, Delaney PV, Healy TM: Evidence for a transmissible agent in Crohn's disease. Gut 18:360–363, 1977 Levi AJ: Diet in the management of Crohn's disease. Gut 26:985–988, 1985 Cave DR, Mitchell DN, Kane SP, Brooke BN: Further animal evidence of a transmissible agent in Crohn's disease. Lancet 2:1120–1122, 1973 Graham DY, Markesich DC, Yoshimura HH: Mycobacteria and inflammatory bowel disease. Gastroenterology 92:436–442, 1987 Kruiningen HJ, Chiodini RJ, Thayer WR, Coutu JA, Merkal RS, Runnels PL: Experimental disease in infant goats induced by a mycobacterium isolated from a patient with Crohn's disease. Dig Dis Sci 31:1351–1360, 1986 Yawalkar SJ, Vischer W: Lamprene (clofazimine) in leprosy. Lepr Rev 50:135–144, 1979 Kelleher D, O'Brien S, Weir DG: Preliminary trial of clofazimine in chronic inflammatory bowel disease. Gut 23:A449, 1982 O'Donoghue DP, Dawson AM, Powell-Tuck J, Bowen RL, Lennard-Jones JE: Double blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease. Lancet 2:955–957, 1978 Schultz MG, Rieder HL, Hersh T, Riepe S: Remission of Crohn's disease disease with antimycobacterial chemotherapy. Lancet 2:1391–1392, 1987 Jarnerot G, Rolny P, Wickbom G, Elemayehu G: Antimycobacterial chemotherapy ineffective in Crohn's disease after one year. Lancet 1:164–165, 1989 Piccioto A, Gesu GP, Schito GC, Testa R, Varagona G, Celle G: Antimycobacterial chemotherapy in two cases of inflammatory bowel disease. Lancet 1:536–537, 1988 Shaffer JL, Hughes S, Linaker BD, Baker RD, Turnberg LA: Controlled trial of rifampicin and ethambutol in Crohn's disease. Gut 25:203–205, 1984 Chiodini RJ, van Kruiningen HJ, Thayer WR, Merkal RS, Couteau JA: Possible role of mycobacteria in inflammatory bowel disease. An unclassified mycobacterial species isolated from patients with Crohn's disease. Dig Dis Sci 29:1073–1079, 1984 Chiodini RJ, van Kruiningen HJ, Thayer WR, Merkal RS, Couteau JA: Characteristics of an unclassified mycobacterial species isolated from patients with Crohn's disease. J Clin Microbiol 20:966–971, 1984 McFadden JJ, Butcher PD, Chiodini R, Hermon-Taylor J: Crohns disease isolated mycobacteria are identical toMycobacterium paratuberculosis, as determined by DNA probes that distinguish between mycobacterial species. J Clin Microbiol 25:796–801, 1987 Meissner GK, Schroder KH, Amadio GE, Anz W, Chaparas S, Engel HW, Jenkins PA, Kappler W, Kleeberg HH, Kubala E, Kubin M, Lauterbach D, Lind A, Magnusson M, Mikova Z, Pattyn SR, Schaefer WB, Stanford JL, Tsukamura M, Wayne LG, Willers I, Wolinsky E: A cooperative numerical analysis of nonscoto-and nonphochromogenic slowly growing mycobacteria. J Gen Microbiol 83:207–235, 1974 Schneebaum CW, Novick DM, Chabon AB, Strutynsky N, Yancovitz SR, Freund S: Terminal ileitis associated withMycobacterium avium-intracellulare infection in a homosexual man with AIDS: Gastroenterology 92:1127–1132, 1987 Gatti JC, Cardama JI, Belima LM: Treatment of leprosy with B 663. Lepr Rev 41:89–92, 1970 Ganghadaram PR, Perumal VK, Jairam BT, Rao PN, Nguyen AK, Farhi DC, Iseman MD: Activity of rifabutine alone or in combination with clofazimine or ethambutol or both against acute and chronic experimentalMycobacterium intracellulare infections. Am Rev Respir Dis 136:329–333, 1987 Masur H, Tuazon C, Gill V, Grimes G, Baird B, Fauci AS, Lane HC: Effect of combined clofazimine and ansamycin therapy onMycobacterium avium intracellulare bacteremia in patienst with AIDS. J Infect Dis 155:127–129, 1987 Anderson R, Lukey P, Van Rensburg C, Dippenaar U: Clofazimine meediated regulation of human polymorphonuclear leukocyte migration by pro-oxidative inactivation of both leukoattractants and cellular migratory responsiveness. Int J Immunopharmacol 8:605–620, 1986 Zeiss BM, Anderson R: Clofazimine mediated stimulation of prostaglandin synthesis and free radical production as novel mechanisms of drug induced immunosuppression. Int J Immunopharmacol 8:731–739, 1986 Niwa Y, Sakani T, Miyachi Y, Ozaki M: Oxygen metabolism in phagocytes of leprotic patients: Enhanced endogenous superoxide dismutase activity and hydroxyl radical generation by clofazimine. J Clin Microbiol 20:837–842, 1984 Bentley G, Webster JHH: Gastrointestinal tuberculosis—a 10 year review. Br J Surg 54:90–96, 1967 Chiodini RJ, van Kruiningen HJ, Merkal RS: Ruminant paratuberculosis (Johnes disease); the current status and future prospects. Cornell Vet 74:218–262, 1984 Gilmour NJL: The effect of the riminophenazine B663 on preclinicalM. johnei infections in sheep. Br Vet J 124:492–497, 1968 Gilmour NJL, Angus KW: Effect of the riminophenazine B663 onM. johnei infection and reinfection in sheep. 1. Bacteriology and hypersensitivity. J Comp Pathol 81:221–226, 1971 Merkal RS, Larsen AB: Clofazimine treatment of cows naturally infected with mycobacterium paratuberculosis. Am J Vet Res 34:27–28, 1973 Rankin JD: Isoniazid; its effect onM. johnei in vitro and its failure to cure clinical Johnes disease in cattle. Vet Rec 65:649–651, 1953 Rankin JD: An attempt to prevent the establishment ofM. paratuberculosis in calves by means of isoniazid alone and in combination with streptomycin. Vet Rec 67:1105–1107, 1955 Chiodini RJ: Bactericidal activities of various antimicrobial agents against human and animal isolates ofMycobacterium paratuberculosis. Antimicrob Agents Chemother 34:366–367, 1990 Chiodini RJ, Van Kruiningen HJ, Thayer WR. Coutu JA, Merkal RS:In vitro antimicrobial susceptibility of aMycobacterium sp. isolated from patients with Crohn's disease. Antimicrob Agents Chemother 26:930–932, 1984 Hampson SJ, Parker MC, Saverymuttu SH, Joseph AE, McFadden JP, Hermon-Taylor J: Quadruple antimycobacterial chemotherapy in Crohn's disease: Results at 9 months in a study of 20 patients. Aliment Pharmacol Ther 3:343–352, 1989 Hornick DB, Dayton CS, Bedell GN, Fick RB: Nontuberculous mycobacterial lung disease: Substantiation of a less agressive approach. Chest 93:550–555, 1988