Short‐ and long‐term outcome of patients treated with cyclosporin for severe acute ulcerative colitis

Abstract

INTRODUCTIONStandard treatment for severe acute exacerbations of ulcerative colitis has changed little over the last 20 years. The treatment consists of either oral, rectal or intravenous corticosteroids and 5-aminosalicylic acid compounds. Patients who do not respond to this treatment will usually be referred for colectomy. Antimetabolites such as azathioprine and 6-mercaptopurine are effective in corticosteroid-dependent disease, but because of their slow onset of action (mean 4 months) are of limited use for acute exacerbations. Approximately 15% of patients with acute ulcerative colitis will require hospital admission for control of symptoms and up to 40% of these will require colectomy. 1,2 There is preliminary evidence over recent years suggesting that the immunosuppressive drug cyclosporin SUMMARY Background: Recent evidence suggests that the immunosuppressive drug cyclosporin may be of bene®t in treating patients with severe colitis who are steroid resistant. Although cyclosporin appears to be effective in reducing colectomy rates in the short term, few data are available on the long-term follow-up of such patients. Aim: To investigate the short-and long-term outcome of patients with severe steroid-resistant ulcerative colitis treated with cyclosporin who were otherwise being considered for colectomy. Methods: Twenty-two patients with severe steroid-resistant exacerbations of ulcerative colitis who were being considered for colectomy were treated with cyclosporin (4 mg/kg i.v.) daily for 7 days followed by oral treatment (6 mg/kg/day) if colectomy was avoided. Results: Twenty of 22 patients (91%) avoided colectomy during their initial hospital admission. With a mean follow-up period of 39 months (range 31±59), eight of these patients have subsequently relapsed and required

Effect of oral tacrolimus (FK 506) on steroid‐refractory moderate/severe ulcerative colitis

“…19.0 ± 0.4 (17)(18)(19)(20)(21) 15.2 ± 0.7 (12)(13)(14)(15)(16)(17)(18) 14.4 ± 1.2 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) 12.9 ± 0.7 (10)(11)(12)(13)(14)(15)(16)(17) 11.6 ± 0.80 (10-17)…”

“…In these studies, however, different criteria for the definition of severe UC were used. 8,15,18 Disease activity was less than severe in part of the population studied, 24 or no definition for severe disease was provided. 2 Several points further indicate the notion that disease activity in our patients was comparable to most of the studies above.…”

“…Furthermore, in several studies on severe UC providing detailed clinical data, various determinants of disease activity of UC, such as CRP, erythrocyte sedimentation rate (ESR), hemoglobin levels (Hb), serum albumin levels, number of bowel movements and blood in the stool, were similar as observed in the patients reported herein. 15,18,24 Third, steroid-refractory UC was defined as no response to a systemic steroid treatment for at least 7 days. The duration of steroid treatment used by most studies investigating immunosuppressive therapy in severe UC 2,8,9,13,15,18,20,23)26 was similar to the duration in our study, and many authors suggest that in cases with no response to a 7-10 day therapy with systemic steroid therapy, alternative therapies should be considered.…”

“…15,18,24 Third, steroid-refractory UC was defined as no response to a systemic steroid treatment for at least 7 days. The duration of steroid treatment used by most studies investigating immunosuppressive therapy in severe UC 2,8,9,13,15,18,20,23)26 was similar to the duration in our study, and many authors suggest that in cases with no response to a 7-10 day therapy with systemic steroid therapy, alternative therapies should be considered. [27][28][29] Nevertheless, it is possible that some patients were slowly entering remission on steroid treatment and would have responded without tacrolimus.…”

“…At baseline, we also determined disease activity using the classic TW criteria, 14 and accordingly graded the colitis as severe if three or more of the following were present: (I) the passage of six or more stools per day; (II) temperature > 37°C; (III) tachycardia > 90 beats/min; (IV) anemia of < 75% of normal hemoglobin levels; (V) an erythrocyte sedimentation rate of > 30 mm/h. 15 With initiation of tacrolimus patients were weaned off steroids. Steroids were withdrawn by a dose reduction of 10 mg/week; in patients with persistent higher disease activity steroids were tapered more slowly.…”