Local injection of infliximab in severe fistulating perianal Crohn's disease: an open uncontrolled study.

BACKGROUND: Perianal fistulas are frequent complications of Crohn's disease. Intravenous infliximab can control perianal disease and promote perianal fistula closure. Perifistular infliximab injections have been proposed for patients who are intolerant or unresponsive to intravenous therapy. The aim of this study was to assess the long-term efficacy of surgical treatment combined with local infliximab therapy. METHODS: A prospective cohort study was designed. Twelve patients with Crohn's disease and high/complex transphincteric and intrasphincteric perianal fistulas refractory to other treatment were submitted to core-out fistulectomies, plus perifistular injections of infliximab (20-25 mg in 15-20 ml of 5% glucose) every 4-6 weeks. The main outcome measure was the clinical closure of all perianal fistulas. A 95% confidence interval was calculated for short- and long-term fistula closure rates. RESULTS: None of the procedures were associated with local or systemic adverse effects. Four patients did not complete treatment, two because of relapse of intestinal symptoms, which required intravenous infliximab. In one case, treatment with intravenous infliximab was complicated by a hypersensitivity reaction. Eight patients continued treatment until all perianal fistulas were closed and setons were removed (median: 5 sessions). Persistent closure was observed in seven (87.5%, 95% CI: 47.4-99.6) of the eight patients 12 months after completion of treatment and in five (62.5%; 95% CI: 24.5-91.5) of eight at the end of follow-up (range: 19-43 months, median: 35 months). CONCLUSIONS: The cohort we examined is small, but fistulectomy combined with repeated perifistular injections of infliximab appears to be safe and may help in fistula healing. However, in most patients, permanent closure of all fistulas is not achieved.

Infliximab in the treatment of Crohn's disease: predictors of response in an Italian multicentric open study.

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.

Anti-tumour necrosis factor alpha (infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients.

BACKGROUND: Conventional treatment options for patients with severe steroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently burdened by toxicity, or colectomy. Preliminary data suggest a benefit from anti-tumour necrosis factor alpha (Infliximab) therapy in patients with steroid refractory ulcerative colitis. AIM: To evaluate the efficacy of Infliximab in the treatment of severe ulcerative colitis refractory to conventional therapy PATIENTS AND METHODS: A series of 13 patients with severe ulcerative colitis, refractory to therapy with methyl-prednisolone, 60 mg daily for seven or more days, were treated with a single intravenous infusion of Infliximab 5 mg/kg. RESULTS AND CONCLUSIONS: Of these 13 patients, 10 (77%) had a clinical response to therapy defined by a clinical activity index 10 on two consecutive days. In 2 patients (15%) total colectomy was necessary on account of clinical worsening whilst one patient refused surgery and was lost to follow-up. All patients who responded showed very rapid clinical improvement, within 2 to 3 days of infusion. Infusion with Infliximab produced no significant adverse events. The mean time of follow-up was 10.1 months (range 5-12; during this time, 9 out of 10 patients (90%) maintained clinical remission and were able to discontinue corticosteroid therapy. Infliximab appears to be an effective agent for inducing long-standing remission in refractory patients with severe ulcerative colitis.

Infliximab in the treatment of severe ulcerative colitis: a follow-up study.

Conventional treatment options for patients with severe steroid-refractory ulcerative colitis (UC) include intravenous cyclosporine, which is frequently burdened by toxicity, or colectomy. Preliminary data suggest a benefit of anti-tumor necrosis factor alpha (Infliximab) therapy in patients with steroid refractory UC. Thirteen patients with severe UC, refractory to therapy with methyl-prednisolone, 60 mg IV daily were treated with a single intravenous infusion of Infliximab 5 mg/kg. Ten out of 13 patients (77%) had a clinical response to therapy defined by a CAI < or = 10 on two consecutive days. Two patients (15%) underwent total colectomy because of clinical worsening; one patient refused surgery and was lost to follow-up. Infusion with Infliximab produced no significant adverse events. The mean time of follow-up was 25.6 months (range 17-24); in this period of time 8 out of 10 patients (80%) maintained clinical remission and were able to discontinue corticosteroids therapy. Infliximab appears to be an effective agent for inducing long standing remission in refractory patients with severe UC.

Prediction of surgery for obstruction in Crohn's ileitis. A study of 64 patients.

The charts of 64 patients with Crohn's ileitis were reviewed to determine what characteristics at the time of first observation at a specialized center were predictive of surgery for irreversible obstruction, using Cox's proportional hazard model. Individual variables which proved significant (P less than 0.01) included age at presentation to the clinic, serum albumin, sedimentation rate, and the presence of radiologic strictures. Patients eventually requiring surgery were older than the rest because of a later date of symptom onset; furthermore, patients with strictures on initial x-rays had not been ill for a longer period of time than those who did not have strictures. These data suggest that fibrosis and stenosis are characteristic of a subgroup of Crohn's patients, rather than being inevitable phases of disease evolution. Multivariate analysis revealed that patients with low serum albumin, high sedimentation rate, and roentgenologic stenosis at first observation were ten times as likely to require surgery for obstruction at 10 years than those without any of these three unfavorable parameters.

Analysis of clinical course of postoperative recurrence in Crohn's disease of distal ileum.

In the present study we have investigated whether in patients with Crohn's Disease the clinical course remains the same from the initial disease to postoperative recurrent disease. Fifty-eight resected patients who developed a postoperative recurrence were followed for 4.2 +/- 3 years (median 3 years). The yearly frequency of flare-up was 1.9 +/- 1.0 (median 1.5) in the initial disease and 1.7 +/- 1.0 (median 1.7) in recurrent disease. In patients who experienced complications during the initial disease, the frequency of complications during the course of recurrent disease was significantly higher than in the others (27/42 vs 3/16, P = 0.002). The frequency of obstruction and extraintestinal manifestations in the recurrent disease was higher in patients who suffered these complications in the initial disease than in those who did not (19/29 vs 6/29, P = 0.0006, and 4/5 vs 4/53, P = 0.0008). The cumulative probability of complication during the course of recurrent disease was higher in patients with complications during the initial disease (P less than 0.001). The survival analysis showed that the cumulative probability of obstruction and extraintestinal complication in recurrent disease was higher in patients who suffered these complications in the initial disease (P less than 0.005). These data indicate that the clinical course of Crohn's disease of the distal ileum remains the same from the initial disease to postoperative recurrent disease. This study also suggests that the short-term course of recurrent disease can reasonably be predicted.

[Radiologic assessment of extent of ulcerative colitis in acute phase]. / Valutazione radiologica dell'estensione della colite ulcerosa nella fase acuta.

One of the major reference points for both prognosis and treatment of ulcerative colitis is the assessment of its extent. Plain abdominal radiographs were performed on 97 patients previously diagnosed, by means of rectoscopy and histobiopsy, as having acute ulcerative colitis. Within the following 36 hours they underwent either full colonoscopy or colectomy. The extent of colitis was evaluated by means of double-blind radiography. The results were then statistically compared with those obtained from endoscopy or from direct study of surgical colonic specimens. There was agreement between the final X-ray results and the actual extent of ulcerative colitis in 78 of 97 patients (80.4%, r = 0.86). The highest agreement was observed in those patients whose lesions were localized in the rectosigma (81%) and in those with fully extended colitis (90%). The most useful radiological findings in predicting the extent of colic lesions were irregular mucosal profile and thickening of colic wall. The presence of these two signs, together with the flattening or swelling of interhaustral folds and the impossible visualization of the right colon, are invariably suggestive of fully extended colitis. On the contrary, no abnormal findings were present on plain abdominal films in 74% of proctosigmoiditis cases. Plain abdominal radiography seems to be useful for the initial evaluation of acute ulcerative colitis. It allows the early discrimination between diffuse and localized forms, and makes it possible to postpone more invasive and dangerous investigations to a remissive phase of the disease.