Effect of infliximab in the treatment of refractory inflammatory bowel disease with complication]

BACKGROUND/AIMS: Many studies on infliximab have confirmed its efficacy in the remission induction and even maintenance in refractory and fistulizing Crohn's disease. We report the treatment efficacy of infliximab in Crohn's disease and ulcerative colitis refractory to steroid treatment and the complications of infliximab treatment. METHODS: We performed infliximab administration in 5 cases (3 Crohn's disease, 2 ulcerative colitis) refractory to systemic steroid treatment and 5 cases of Crohn's disease with fistula. Patients received an intravenous infusion of infliximab at 3-5 mg/kg body weight. RESULTS: In 3 cases of refractory Crohn's patients, clinical response and remission induction were obtained in 2 (67%) and 1 cases (33%). After infusion of infliximab, the occlusion of internal fistula could be found in all 2 cases. Two out of 3 cases of anal fistula were completely healed. In two cases of refractory ulcerative colitis, one case who showed clinical manifestation of toxic megacolon had improved and avoided the colectomy, but the other case did not respond to the infusion of infliximab and underwent colon resection. CONCLUSIONS: We found that administration of infliximab is an effective alternative for refractory and fistulizing Crohn's disease but further studies are necessary for refractory ulcerative colitis.     

英夫力西单抗治疗难治性溃疡性结肠炎

目的分析14例英夫力西治疗难治性中重度溃疡性结肠炎的临床资料,探索英夫力西治疗国人溃疡性结肠炎的效果和安全性。方法对我院2006年-2011年经常规治疗失败的14例难治性中重度溃疡性结肠炎患者,行英夫力西单抗治疗,分别于0、2、6周按5 mg/kg全身用药,以后每8周给药1次,个别患者因用药效果、病情变化等增加了用药剂量或缩短了用药间隔。分析英夫力西单抗治疗8周有效率和缓解率,随访30周、54周缓解率及安全性等。结果治疗8周有效率为42.9%,缓解率为42.9%,无效率为14.3%;随访30周、54周缓解率分别为57.1%和42.3%。有2例患者达到黏膜愈合,至今分别随访35个月和28个月,病情均无复发。不良反应发生率为28.6%,无严重或危及生命的不良反应发生。随访54周,有效组和无效组前两次英夫力西单抗治疗有效者所占比例差异有统计学意义(P=0.015)。结论应用英夫力西治疗14例难治性中重度溃疡性结肠炎,取得了良好的治疗效果,前两次治疗有效可预示远期治疗效果好,近期的药物不良反应不影响程序性治疗的进行。英夫力西单抗可作为国人难治性溃疡性结肠炎的挽救治疗方法。     

Infliximab for patients with refractory ulcerative colitis

Conventional treatment options for patients with severe corticosteroid-refractory ulcerative colitis (UC) include intravenous cyclosporine, which is frequently limited by toxicity, or colectomy. The efficacy of infliximab was investigated in the treatment of 16 patients with severely active UC refractory to conventional therapy; 7 of these patients were considered for colectomy pending medical failure. All patients received a single infusion of infliximab, 5 mg/kg; 6 of 16 patients (38%) received a second infusion approximately 5 months later. Efficacy was assessed by clinical response (defined as the lack of symptoms) as well as endoscopic and histologic outcomes. Clinical, endoscopic, and histologic improvement was observed in 14 of 16 patients (88%) after treatment with infliximab. Surgery was avoided in six of seven surgical candidates (86%). Clinical remission was maintained in 14 of 16 patients (88%) for > or = 4 months, and 4 of 16 patients (25%) for 7-10 months. Most of the treated patients were completely withdrawn from corticosteroid therapy. Treatment with infliximab induced endoscopic remission at 30 days and a significant improvement from baseline in mean histologic score (p < 0.001). In conclusion, infliximab improved clinical, endoscopic, and histologic outcomes in patients with severely active UC refractory to conventional therapy, allowing corticosteroid sparing and reducing the need for colectomy.     

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 for treatment of steroid-refractory ulcerative colitis

BACKGROUND: Success achieved in two subtypes of Crohn's disease has persuaded a few investigators to experiment the monoclonal anti-tumour necrosis factor antibody infliximab in the treatment of ulcerative colitis. So far, however, the results (achieved in some 30 steroid-refractory patients included in two independent full-papers) indicate a rate of initial response of 50% and of remission of 25%. AIMS: To analyse data of an open trial conducted on consecutive steroid-refractory severely ill patients admitted to our referral Unit. PATIENTS AND METHODS: In 9 months, infliximab was given to 8 patients (4 male, 4 female aged 20-60 years) with uncontrolled ulcerative colitis of whom 6 were non-responders to parenteral steroids. All received the first infliximab dose as an intravenous infusion of 5 mg/kg. RESULTS: Of the 8, 4 (50%) did not respond to the first injection and were submitted to urgent colectomy; the other four responded clinically. Two have maintained clinical remission for 7 months, without the need for steroids; both have received daily azathioprine at 2 mg/kg, and only one has received two further infliximab injections. Of the other two, one received a second injection at week 5, despite this relapsed, and underwent elective colectomy at that time; the other relapsed at 6 months and showed a partial response to a repeat infliximab infusion. Thus, the rate of sustained response is 2/8 (25%) in this study. CONCLUSION: These results, achieved in an open uncontrolled fashion, seem to reflect those of other independent studies. In our opinion, these findings warrant an in-depth reappraisal of the indication to use infliximab as rescue treatment for refractory ulcerative colitis.     

Cyclosporine Therapy as a Rescue Treatment in Steroid Refractory Acute Severe Ulcerative Colitis: A Real Life Data From a Tertiary Center

Background:Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative ­colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients.Methods:Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylprednisolone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index.Results:In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, ­respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy.Conclusion: Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.     

All that bleeds is not infliximab-refractory ulcerative colitis

The role of biological agents in moderate to severe ulcerative colitis has been shown to be effective in the induction of clinical remission. However, the role of infliximab therapy for induction of remission in patients with fulminant colitis is debatable. A case of a hospitalized patient with a new diagnosis of severe ulcerative colitis refractory to intravenous steroids is presented. The patient was treated with infliximab and discharged with clinical remission, but subsequently presented back to hospital with a lower gastrointestinal hemorrhage.     

Adalimumab induction therapy for ulcerative colitis with intolerance or lost response to infliximab： An open-label study

AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant. METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4. RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4. CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebo- controlled trials.     

Previous infliximab therapy and postoperative complications after proctocolectomy with ileum pouch anal anastomosis

Background and aimsIt is unclear whether infliximab treatment induces increased complication rates after surgery for ulcerative colitis. Aim was to compare complication rates after pouch surgery in refractory ulcerative colitis patients with versus without previous infliximab therapy.MethodsWe performed a retrospective study evaluating all patients who underwent an ileoanal J-pouch for refractory ulcerative colitis over a four-year period. Postoperative complications, infliximab use and time between last infliximab administration and restorative surgery were assessed. 1-stage procedures (proctocolectomy with pouch, with or without temporary diversion) and 2-stage procedures (emergency colectomy and subsequent completion proctectomy with pouch, with or without temporary diversion) were analyzed separately.ResultsSeventy-two patients were included; 33 underwent 1-stage procedure and 39 had 2-stage surgery. In the 1-stage group, 21 patients (64%) had previous infliximab therapy (median time between last infusion and surgery: 7.1 months (IQR 2.6-8.3)). Infliximab-treated patients had higher incidence of pelvic sepsis (5/21 vs. 0/12; risk difference 24%; 95% CI: 6 to 42, p = 0.067) and non-infectious complications (8/21 vs. 1/12; risk difference 30%; 95% CI: 4 to 56, p = 0.065). In the 2-stage group, 17 (44%) had previous infliximab therapy (median time between last infusion and surgery: 11.8 months (IQR 7.3-15.5)). Total, infectious, non-infectious complication rates and pelvic sepsis rates were similar for infliximab and non-infliximab patients in the 2-stage group.ConclusionsThis small study suggests that infliximab use prior to 1-stage restorative proctocolectomy in patients with UC is associated with increased incidence of pelvic sepsis. A 2-stage procedure in these patients should be considered.     

Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis

AIM:To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis(UC)patients.METHODS:This was a prospective,multicenter,observational study.Between May 2010 and August 2012,49 steroid-refractory UC patients(55 flare-ups)were consecutively enrolled.All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1mg/kg per day.The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/m L for the first 2 wk.Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index(CAI).RESULTS:The mean CAI was 12.6±3.6 at onset.Within the first 7 d,93.5%of patients maintained high trough levels(10-15 ng/m L).The CAI significantly decreased beginning 2 d after treatment initiation.At 2wk,73.1%of patients experienced clinical responses.After tacrolimus initiation,31.4%and 75.6%of patients achieved clinical remission at 2 and 4 wk,respectively.Treatment was well tolerated.CONCLUSION:Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation.Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.     

Tacrolimus induction followed by maintenance monotherapy is useful in selected patients with moderate-to-severe ulcerative colitis refractory to prior treatment

Background

Tacrolimus in refractory ulcerative colitis often serves as a bridge to long-term maintenance therapy with thiopurines. Our aim was to review efficacy and safety of tacrolimus in active ulcerative colitis resistant to conventional therapies, including anti-tumour necrosis factor.

Methods

Charts of consecutive outpatients with refractory ulcerative colitis, in whom tacrolimus was orally administered as a 12 week-induction (target trough levels 10–15 ng/mL) followed by a maintenance therapy (target trough levels 5–10 ng/mL), were retrospectively reviewed. Clinical remission and response at weeks 4, 12 and 52 as well as adverse events within 1-year therapy were reported.

Results

Twelve (40%) and six (20%) of the 30 patients included (14 males, mean age 37.1 ± 1.4 years) achieved a clinical remission and response, respectively, at week 12. Three responders to tacrolimus initiation experienced drug-related adverse events requiring discontinuation. Among the 18 remaining initial responders who tolerated tacrolimus, 8 (27%) were in clinical remission at week 52, whereas the remainder either experienced adverse events requiring drug withdrawal (n = 4) or relapsed (n = 6). Overall adverse events were recorded in 14 patients (46%), mainly finger tremor and urinary infections.

Conclusion

Oral monotherapy with tacrolimus may be a valuable long-term therapeutic option in selected patients with moderate-to-severe active refractory ulcerative colitis.     

Inflammatory bowel disease patients are frequently nonadherent to scheduled induction and maintenance infliximab therapy: A Canadian cohort study

BACKGROUND:

Adherence to maintenance medication regimens in inflammatory bowel disease patients has traditionally been poor. Although infliximab has demonstrated efficacy in inducing and maintaining disease remission, adherence to regularly scheduled infliximab infusions is required to maintain therapeutic trough drug levels and prevent the development of anti-infliximab antibodies.

OBJECTIVES:

To characterize patient adherence to regularly scheduled induction and maintenance infliximab infusions.

METHODS:

A retrospective cohort study was conducted evaluating adult outpatients with Crohn disease or ulcerative colitis on an induction or maintenance regimen of regularly scheduled infliximab from 2008 to 2010 at the University of Alberta (Edmonton, Alberta). Nonadherence was defined by a discrepancy of >72 h between the scheduled date of infusion and the actual date of administration. Patients were defined as nonadherent if they received <80% of their infliximab infusions per schedule.

RESULTS:

A total of 215 patients (173 Crohn disease, 42 ulcerative colitis) met the inclusion criteria. Patients received a median of 12.0 infliximab infusions (interquartile range 7.0 to 13.0) during the study period; 412 induction and 1837 maintenance infliximab infusions were administered. Of 140 patients, 109 (77.9%) were adherent to their infliximab induction regimen, while 68 of 215 (31.6%) were adherent to their infliximab maintenance regimen. One hundred ninety-eight of 215 (92.1%) patients received at least one delayed maintenance infliximab infusion and 20 (10.1%) received maintenance infusions, on average, >1 week late.

CONCLUSIONS:

While three-quarters of patients are adherent to infliximab induction therapy, fewer than one-third remained adherent to their scheduled maintenance infliximab regimen.     

Infliximab induces clinical, endoscopic and histological responses in refractory ulcerative colitis.

BACKGROUND: infliximab is a monoclonal antiTNF-ct antibody that has repeatedly shown to be effective in the management of Crohn's disease. However, data are scarce about its efficacy in ulcerative colitis. AIM: to describe the joint experience of three Spanish hospitals in the use of infliximab in patients with active refractory ulcerative colitis. PATIENTS AND METHODS: we present seven cases of ulcerative colitis (6 with chronic active disease despite immunosuppressive therapy, and one with acute steroid-refractory ulcerative colitis) treated with infliximab 5 mg/kg of body weight. Clinical response was evaluated by means of the Clinical Activity Index at 2, 4 and 8 weeks after initial infusion. Biochemical (erythrocyte sedimentation rate and C-reactive protein), endoscopic, and histological changes were also assessed. RESULTS: mean age of patients was 45.8 +/- 17 years (range 23-77); 4 were female. No adverse effects were recorded. Inflammatory activity diminished significantly in 6 of 7 patients (85.7%; CI 95%: 42-99%) both from a clinical (p = 0.01) and biochemical (p <0.05) point of view. Five out of six patients (83.3%; 36-99%) with corticosteroid-dependent disease could be successfully weaned off these drugs. Five patients were endoscopicly controlled both before and after therapy, and a positive endoscopic and histological response could be recorded in all of them. CONCLUSION: infliximab may be an effective and safe therapy for some patients with ulcerative colitis refractory to other forms of therapy, although controlled studies are needed to assess its role in the general management of this disease.     

Efficacy of cyclosporin with corticotropin for refractory ulcerative colitis

BACKGROUND/AIMS: Cyclosporin was reported to be useful for steroid-resistant severe ulcerative colitis in the short term, but limited data are available on the long-term follow-up of such patients. Our aim was to assess the short- and long-term efficacy of combination therapy with cyclosporin and corticotropin for steroid-resistant ulcerative colitis. METHODOLOGY: Twenty-one patients with ulcerative colitis who did not respond to corticosteroid therapy, were treated with corticotropin, and 9 patients (43%) of them achieved complete remission. Twelve patients (57%) who did not achieve complete remission by corticotropin alone were given combination therapy with cyclosporin and corticotropin. RESULTS: In 12 patients who received combined therapy with cyclosporin and corticotropin, clinical severity was distinctly improved in 11 patients (92%) by combination therapy within 2 weeks and 7 patients (58.3%) entered into complete remission with salicylazosulfapyridine or 5-aminosalicylic acid alone. Two patients (16.7%) demonstrated insufficient effect and continue to receive a lower dosage of cyclosporin or corticosteroid. Three patients (25%) failed to respond to the combination therapy and required colectomy. Three of 7 patients who entered into remission relapsed 0.5, 5 and 5.5 months (average: 3.7 months) after cyclosporin withdrawal, but the clinical severity at the time of relapse was milder than that at the beginning of the treatment, namely, moderate in 2 patients, and mild in 1 patient. There were no significant adverse effects in our series. CONCLUSIONS: We demonstrated that oral cyclosporin in combination with corticotropin was highly effective for ulcerative colitis refractory to corticosteroid or corticotropin therapy and severe relapse was uncommon during several years of follow-up.     

Optimizing conventional therapy for inflammatory bowel disease

Recently, conventional therapies for inflammatory bowel disease (IBD) have not received the same amount of attention as biologic therapies, yet they remain the backbone of therapy for IBD because of their efficacy, safety, and relatively low cost. Advances in efficacy and safety continue because of modifications in drug dosing and monitoring. Higher doses of mesalamine per pill, together with once-daily dosing, may help to optimize drug delivery and patient compliance. Budesonide, an effective agent for both induction and short-term remission maintenance in Crohn’s disease, is devoid of many of the toxicities common to corticosteroids. Assessments of thiopurine methyltransferase and metabolite levels are helping to fine-tune dose optimization for the thiopurines azathioprine and 6-mercaptopurine. The oral calcineurin inhibitors tacrolimus and cyclosporine have been shown to have expanded roles in IBD, and methotrexate may be useful in some patients with refractory ulcerative colitis. Probiotics are showing promise for maintenance of remission in Crohn’s disease, ulcerative colitis, and pouchitis.     

Case of ulcerative colitis refractory to intravenous cyclosporine therapy successfully treated with infliximab]

A 26-year-old woman was admitted to our hospital with relapse of ulcerative colitis (UC). We diagnosed it as a refractory UC because intravenous corticosteroid therapy had no effect. Intravenous cyclosporine therapy and other conventional therapies did not lead to remission. Then the possibility of infliximab was discussed with the patient and her parents and treatment with infliximab was started. Infliximab was infused intravenously at a dose of 5mg per kilograms of body weight. Immediately after the first infusion, clinical symptoms improved, and clinical remission was achieved within 12 weeks. It is suggested that infliximab can be effective for refractory UC.     

Longer term outcome of steroid refractory ulcerative colitis treated with intravenous cyclosporine without subsequent oral cyclosporine maintenance therapy

BACKGROUND AND AIMS: Intravenous cyclosporine (Cy) is increasingly used in patients with severe ulcerative colitis who fail to respond to corticosteroids. However, in spite of subsequent oral Cy maintenance therapy almost one-half of the initial responders need colectomy within a year. In light of the drug's limited efficacy and potential toxicity use of oral long-term Cy can be questioned. PATIENTS AND METHODS: Nineteen patients with steroid refractory severe ulcerative colitis were treated intravenously with Cy. RESULTS: Of the 19 patients 14 (76%) achieved remission. Six of the patients (46%) remained in remission for 12-61 months. Eight patients experienced one to four flares during the year after treatment. However, except for one patient who needed another course of intravenous Cy, all responded to corticosteroids. The duration of remission since the last flare in these patients (five received azathioprin) was 10-36 months. None of the patients needed colectomy because of symptoms. CONCLUSION: These preliminary data suggest that a course of intravenous Cy can turn corticosteroid-refractory ulcerative colitis to corticosteroids responsive. The outcome of patients not receiving oral Cy maintenance therapy appears to be satisfactory. Azathioprin maintenance therapy can probably be reserved for select patients.     

Careful patient selection may improve response rates to infliximab in inflammatory bowel disease

BACKGROUND AND AIM: The use of infliximab in the treatment of Crohn's disease (CD) is acceptable and appears to be effective in ulcerative colitis (UC). Careful patient selection, resulting in infliximab only for truly refractory inflammatory bowel disease (IBD), may improve its efficacy. The present study aimed to determine if careful patient selection improved infliximab efficacy in IBD. Methods: CD or UC/IBD unclassified patients (Montreal classification) were considered for infliximab treatment only after failure of disease control with conventional therapies and confirmation of active disease. Patients with purely luminal IBD received a single infliximab dose. Patients with fistulizing disease (with or without luminal disease) received infliximab at 0, 2 and 6 weeks. Changes to Harvey Bradshaw (HBI) for inflammatory CD and Colitis Activity Index (CAI) for UC/IBDU were used to determine the response and remission rates. In fistulizing CD, a remission was sustained cessation of drainage and resolution of the fistula. Response was correlated to inflammatory marker levels. RESULTS: Seventy IBD patients were treated. In CD, 85.2% (46/54) had active luminal and 40.7% (22/54) had fistulizing disease. In luminal CD, at 8 weeks a single infliximab dose induced remission in 75% (24/32) of patients compared to 92.9% (13/14) after infliximab at 0, 2 and 6 weeks. Fistulizing disease responded in 77.2% (17/22) and remitted in 50% (11/22) of patients at 8 weeks. In UC/IBDU, 75% (12/16) responded and 43.8% (7/16) of patients were in remission at 8 weeks. CONCLUSION: Careful patient selection may improve infliximab's efficacy and clinical remission appears greater after induction with three infliximab doses in CD. Clinical efficacy is suggested for UC/IBDU.     

Infliximab for refractory ulcerative colitis

Eight patients with active ulcerative colitis (UC), refractory to usual combination medical therapy, were treated with a single i.v. dose of chimeric monoclonal antibody to recombinant human tumor necrosis factor alpha; many of these patients were scheduled for surgical colectomy because of their active disease. All patients responded extremely well to a single 5 mg/kg infusion of infliximab, with marked improvement after the infusion clinically, colonoscopically, and histologically on colonic biopsy. There were no significant complications or side effects; mean duration of remission has not been determined because none of the patients have relapsed. Infliximab appears to be a potent agent for inducing remission in refractory patients with ulcerative colitis.     

Intravenous azathioprine in severe ulcerative colitis: a pilot study

OBJECTIVE: Azathioprine use in acute ulcerative colitis has been limited by its perceived long onset of action. The aim of this study was to determine the safety and clinical effect of an i.v. loading dose of azathioprine in the setting of severe steroid refractory ulcerative colitis. METHODS: Nine hospitalized patients with severe steroid refractory ulcerative colitis were enrolled. Patients 1-3 received 20 mg/kg i.v. azathioprine over 36 h. Patients 4-6 received 40 mg/kg i.v. azathioprine over 36 h. Patients 7-9 received 40 mg/kg i.v. azathioprine as three 8-h infusions over 3 days. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erythrocyte concentrations of 6-thioguanine were obtained. RESULTS: Five of nine patients (56%) had a response and avoided colectomy. Three of nine patients (33%) met the definition for clinical remission. Response was seen within 4 wk. The mean 6-thioguanine concentration for those five patients at 12 wk after infusion was 148.2 pmol/8 x 10(8). Two patients had transient leukopenia and one had transient hepatotoxicity. CONCLUSIONS: Intravenous azathioprine appears to be safe and of clinical benefit in inducing response and avoiding colectomy in severe steroid refractory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's disease suggests oral dosing alone may obtain the same results. The role of oral dosing alone in severe ulcerative colitis and the role of azathioprine metabolite levels in monitoring efficacy should be investigated further.