Infliximab in treatment of Crohn''s disease: the Milan experience

BACKGROUND: Efficacy of infliximab in treatment of patients with moderate-to-severe refractory and fistulizing Crohn's disease has been shown in controlled clinical trials. Moreover, audit data from North America and North Europe have confirmed efficacy in clinical practice comparable to that in clinical trials. AIM: To report clinical experience using infliximab in treatment of Crohn's disease in Italy, comparing efficacy and safety with those reported in clinical trials and other published series. PATIENTS AND METHODS: The study population comprised 63 patients (31 males and 32 females, median age 33 years) treated with infliximab for refractory/inflammatory (31 patients) and/or fistulizing Crohn's disease (32 patients). All patients received an infusion of infliximab at a dose of 5 mg/kg at weeks 0, 2 and 6. After the first infusion, clinical and laboratory assessments were repeated at weeks 2, 6 and 10. For refractory inflammatory Crohn's disease, clinical remission was defined as a Crohn's Disease Activity Index of < or = 150 at each scheduled visit, clinical response as a reduction in the Crohn's Disease Activity Index score of > or = 70 points in comparison to baseline. For fistulizing Crohn's disease, a complete response was defined as closure of any draining fistulae at week 10. A fistula was defined as closed when it no longer drained despite gentle finger pressure. A partial response was defined as reduction in number, size or drainage of fistulae, at the same visit. RESULTS: According to an intention-to-treat evaluation on the 31 patients with refractory/inflammatory Crohn's disease, at week 2, 42.5% (14 patients) had a clinical response and 31.3% of patients (10 patients) were in clinical remission. At week 10 (4 weeks after the end of third infusion), 80.6% (25 patients) had a clinical response and 71% (22 patients) were in clinical remission and 14/19 (74%) had discontinued steroid treatment. Of the 32 patients with fistulizing Crohn's Disease, 15 (46.9%) had a complete response, 8 (25%) a partial response, and 9 (28.1%) no response at week 10 check-up. The incidence of side-effects was low (16%) and not influenced by concurrent immunomodulatory therapy. CONCLUSION: The present experience with infliximab in clinical practice confirms its efficacy, in particular in inflammatory/refractory Crohn's disease and its safety, at least, in short-term follow-up.     

Successful management of Crohn's disease of the ileoanal pouch with infliximab.

This study reports the clinical benefit and safety of the murine chimeric anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab, in the treatment of patients who developed findings compatible with Crohn's disease after undergoing colectomy with ileal-pouch anal anastomosis (IPAA) for an original diagnosis of ulcerative colitis. Medical records of 7 patients with Crohn's disease and an IPAA treated with infliximab were reviewed. Clinical response was classified as complete response, partial response, and no response. Concurrent treatment with immune modifier agents and/or antibiotics was recorded. Seven patients with active inflammatory or fistulizing Crohn's disease and an IPAA performed for diagnosis of ulcerative colitis were treated with infliximab after they had no response to conventional therapies. Patients received 1-4 infliximab infusions at a dose of 5 mg/kg. All patients improved clinically. Six patients had a complete response, and 1 had a partial response. Four of the 5 patients with complex perianal and fistulizing disease had closure of all fistula tracts, and 1 patient improved temporarily. Six of the 7 patients underwent concurrent treatment with immune modifier drugs. One patient had myalgias and malaise after the first infliximab infusion and flu-like symptoms after the second one. No other adverse effects were observed. This case series demonstrates that the murine chimeric anti-TNF-alpha monoclonal antibody, infliximab, can be used successfully to treat patients with Crohn's disease involving an IPAA who are refractory to conventional therapies.     

Current therapeutic recommendations: infliximab for ulcerative colitis

Randomized, controlled studies have shown that infliximab, the chimeric anti-tumor necrosis factor alpha (TNF-alpha) antibody, is effective for the treatment of active and fistulizing Crohn's disease. Because infliximab is beneficial in patients with Crohn's disease, in whom other therapies have failed, it has been postulated that infliximab may also be helpful in patients with ulcerative colitis. Many investigators have studied the effectiveness of infliximab in ulcerative colitis, mainly in patients who are refractory to corticosteroids. Unfortunately, these studies have not yielded a conclusive answer to the efficacy of infliximab in inducing remission in patients with severe ulcerative colitis. However, some have reported excellent results and others less effective, with the overall data being inconclusive. The purpose of this review is to summarize the current literature on the use of infliximab in ulcerative colitis, as well as to provide insight into the possible mechanisms of why it may or may not work in these difficult-to-treat 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 in the treatment of Crohn's disease: a user's guide for clinicians

Induction therapy with infliximab is indicated for treatment of signs and symptoms, and induction and maintenance of remission in patients with moderate to severely active inflammatory Crohn's disease with an inadequate response to conventional therapy, and for reduction in the number of draining fistulas in patients with fistulizing Crohn's disease. Emerging indications for infliximab therapy in patients with Crohn's disease include maintenance of fistula improvement (reduction in the number of draining perianal or enterocutaneous fistulas) and complete fistula response (no draining fistulas) in patients with fistulizing Crohn's disease, steroid sparing in steroid-treated patients, early use in hospitalized patients who have not failed conventional medical therapy where there is either a severe clinical presentation or a rapid onset of action is desired, and in a variety of unusual and extra-intestinal manifestations of Crohn's disease. An infliximab dose of 5 mg/kg is recommended initally, but some patients who require maintenance dosing may benefit from increasing the infliximab dose over a range of 5-10 mg/kg. An induction regimen of 3 doses at 0, 2, and 6 weeks is the preferred dosing strategy for inducing remission. The optimal dosing interval for patients who require retreatment appears to be every 8 weeks for most patients. Concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate may result in improved outcomes due to a reduction in the frequency of human anti-chimeric antibody formation, acute infusion reactions, and a reduced risk of delayed hypersensitivity-like reactions and formation of antinuclear antibodies. Pretreatment with diphenhydramine (and in selected cases of acetaminophen and, rarely, corticosteroids) is recommended in patients with a history of infusion reactions and patients at risk for delayed hypersensitivity-like reactions. Patients with evidence of active infection should not receive infliximab until the infection is adequately treated, and all patients should be screened for tuberculosis prior to initiating infliximab therapy.     

Clinical outcome of Crohn's disease treated with infliximab

BACKGROUND/AIMS: Controlled studies in humans have shown the role of antibodies to tumor necrosis factor-alpha in the treatment of both fistulizing and inflammatory Crohn's disease. The aim of this study is to report the results of a multicenter clinical trial to evaluate efficacy of infliximab in Crohn's disease patients who are refractory to conservative drugs or fistulizing Crohn's disease. METHODOLOGY: This trial was carried out at 5 university and community hospitals, in Turkey. A total of 25 patients with Crohn's disease that were unresponsive to conventional medical therapy, participated; 17 of the 25 were in the fistulizing disease group and 8 were in the inflammatory disease group. Clinical response was classified according to fistula drainage, diarrhea as positive response or no response. RESULTS: Overall response rate was 92% (23/25), regardless of the disease group, after first infusion of infliximab. Sixteen out of 17 patients in the fistulizing disease group had a positive response. Fourteen of the 16 positive responders later relapsed. Median duration of response was 8 weeks (range, 2-35 wk). Active inflammatory disease patients had a positive response rate of 75% (6/8) and two of the patients were nonresponders. A further two patients relapsed at week 14. Two patients in both arms of the study were still in remission at the end of the study. Major adverse events were: pneumonia in one patient, skin infections in two patients, pulmonary thromboembolism and death in one patient. CONCLUSIONS: Infliximab treatment seems to be more effective in Crohn's disease patients especially in those with fistulizing disease than those with non-fistulizing, inflammatory disease. It is evident that maintenance of remission might be achieved with ongoing maintenance therapy. We suggest maintenance of infliximab therapy.     

Strategies for targeting tumour necrosis factor in IBD

Tumour necrosis factor (TNF) plays an important role in mediating the inflammation of inflammatory bowel disease, in particular, Crohn's disease. Strategies aimed at reducing tumour necrosis factor in patients with inflammatory bowel disease include the mouse/human chimeric monoclonal antibody infliximab, the humanized monoclonal antibody CDP571, the human soluble TNF p55 receptor onercept, the human monoclonal antibody D2E7 (adalimumab), the anti-TNF human antibody Fab' fragment-polyethelene glycol (PEG) conjugate CDP870, and the small molecules thalidomide and CNI-1493 (MAP-kinase inhibitor). Infliximab is effective for treating active Crohn's disease, maintaining remission, closing fistulas, maintaining fistula closure, and treating ankylosing spondylitis. Infliximab is also being investigated for the treatment of ulcerative colitis. Side-effects occurring in patients treated with infliximab include human anti-chimeric antibodies, infusion reactions, delayed hypersensitivity reactions, formation of autoantibodies, and, in rare circumstances, drug-induced lupus and serious infections, including tuberculosis. CDP571 is effective for treating active Crohn's disease, steroid sparing, and possibly for closing fistulas and maintaining remission. Side-effects occurring in patients treated with CDP571 include anti-idiotype antibodies, infusion reactions and the formation of autoantibodies. A controlled trial of etanercept in patients with Crohn's disease was negative. Pilot studies with onercept, thalidomide, and CNI-1493 have suggested benefit for Crohn's disease. There are no published data on the efficacy of adalimumab (D2E7) or CDP870 for either Crohn's disease or ulcerative colitis. Anti-tumour necrosis factor therapies are effective for the treatment of Crohn's disease and are being investigated for ulcerative colitis.     

Infliximab efficacy in pediatric ulcerative colitis

BACKGROUND: The effects of infliximab, a tumor necrosis factor-alpha (TNF-alpha) antibody, have been well established in adult patients with inflammatory and fistulizing Crohn's disease. This study evaluates short- and long-term efficacy of infliximab in children with ulcerative colitis. METHODS: All pediatric patients with ulcerative colitis who received infliximab between July 2001 and November 2003 at the Johns Hopkins Children's Center were identified. Short- and long-term outcomes and adverse reactions were evaluated. RESULTS: Twelve pediatric patients with ulcerative colitis received infliximab for treatment of fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid-dependent colitis (5), and steroid-refractory colitis (1). Nine patients had a complete short-term response, and 3 had partial improvement. The mean per patient dose of corticosteroid after the first infliximab infusion decreased from 45 mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day at 8 weeks (P = 0.008). Eight patients were classified as long-term responders with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3 underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long-term nonresponders were steroid-refractory compared with 1 of 8 long-term responders. Patients receiving 6-mercaptopurine had a better response to infliximab. CONCLUSION: Infliximab should be considered in the treatment of children with symptoms of acute moderate to severe ulcerative colitis.     

Efficacy and safety of infliximab as rescue therapy for ulcerative colitis refractory to tacrolimus

Background and Aim: Little is known about the efficacy and safety of infliximab for ulcerative colitis refractory to tacrolimus. The aim of this study was to evaluate the efficacy and safety of infliximab in the induction of remission in ulcerative colitis patients with persistent symptoms despite tacrolimus therapy. Methods: We report a retrospective, observational, single‐center case series of 12 consecutively enrolled patients with ulcerative colitis refractory to tacrolimus that received infliximab therapy for the induction of remission. Eight patients received a single infusion of infliximab, and four received two or more infusions. Median follow‐up duration was 16.0 months (range, 1.6–41.4 months). The clinical response was evaluated based on a modified Truelove‐Witts severity index. Results: Six patients (50.0%) achieved clinical remission within 30 days. Overall cumulative colectomy‐free survival was estimated to be 58.3% at 41.4 months. Adverse events included an elevation of liver enzymes (1/12; 8.3%) and a mild infusion reaction (1/12; 8.3%). No mortality occurred. Conclusions: Infliximab can induce remission in patients with ulcerative colitis who do not tolerate or respond to tacrolimus therapy.     

Safety of biologic therapy

Several biologic agents have been assessed in patients with inflammatory bowel disease (IBD; Crohn's disease [CD] and ulcerative colitis [UC]). Until recently, only infliximab (humanized monoclonal anti-TNF-alpha antibody) had been approved by the Food and Drug Administration (FDA) to induce and maintain remission in patients with active mild to moderate and/or fistulizing Crohn's disease who are refractory to conventional therapy. Two recent trials, ACT 1 and ACT2, observed high efficacy of infliximab in inducing and maintaining clinical remission, mucosal healing, and corticosteroid-sparing effects in patients with moderate to severe UC. This agent also was recently approved by the FDA for the treatment of ulcerative colitis to reduce signs and symptoms, to induce clinical remission and healing of the intestinal mucosa, and to eliminate the use of corticosteroids in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. There have been many randomized, double-blind, controlled and open-label uncontrolled studies of large and small numbers of patients assessing the efficacy and safety of various biologic agents considered potentially useful in the treatment of IBD. Among all the biologic agents, infliximab has the most robust data on safety. This is because it has been evaluated in many more trials than has any other biologic agent. In addition, postmarketing experience provides very valuable information about adverse events occurring during treatment with this agent.     

Pulse cyclophosphamide therapy for inflammatory bowel disease

AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD).METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800mg) per month.RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d).CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.     

Pulse cyclophosphamide therapy for inflammatory bowel disease

AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD). METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800 mg) per month. RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d). CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.     

Infliximab treatment and prognostic factors for response in patients with Crohn's disease.

OBJECTIVE: The aim of this study is to report our experience with infliximab and analyse prognostic factors for response in Crohn's disease (CD). MATERIAL AND METHODS: Consecutive patients were prospectively enrolled in the study when referred for infliximab infusion. Data collected included indication for infusion, patient epidemiological characteristics, Vienna classification, previous surgery, previous medications and extra-intestinal manifestations. Adverse events and clinical response were tabulated separately for patients with luminal or fistulous Crohn's disease. RESULTS: 28 patients were treated (7 with inflammatory and 21 with fistulizing disease). Patients received a total of 116 infusions of infliximab: 57.1% (4 of 7) of patients with luminal disease had complete response within a median of 17.5 days (range 15-28 days), and 62% (13 of 21) of patients with fistulizing disease had complete response within a median of 9 days (range 6-51 days). All patients (5) without relapse received concomitant treatment with immune modifiers. The group of patients with previous resection or perianal fistula repair had complete response more frequently p = 0.03 (OR = 30; IC 95% = 1.47-119.8). CONCLUSIONS: Infliximab is safe and beneficial in clinical practice for Crohn's disease. The re-treatment regimen of infliximab is effective in maintaining clinical response. Immunosuppressant therapy may have a role in the duration of maintained clinical remission in patients with fistulizing disease. In patients with perianal fistulizing disease infliximab treatment is more effective when previous resection or fistula repair is present.     

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。     

Use of methotrexate in inflammatory bowel disease in 2014: A User's Guide

Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.     

Recent advances in the management of Crohn's disease.

In the last 10 years many advances have been achieved in the treatment of patients with Crohn's disease, particularly in the field of biological agents. Infliximab, a tumour necrosis factor alpha antagonist, has been recently added to the therapeutic armamentarium for Crohn's disease and has greatly improved our treatment options. Infliximab has demonstrated efficacy in the induction and maintenance of remission in luminal and fistulizing Crohn's disease both in adults and children. However, the potential development of autoantibodies and the risk of serious adverse events limit the possibility of a wider use of infliximab. Searching for less immunogenicity and higher effectiveness in the last years a number of biological agents have been developed. Adalimumab, a fully human monoclonal antibody anti tumour necrosis factor alpha, has resulted effective and safe in patients with Crohn's disease, both naive and refractory to infliximab, presenting also the advantage of subcutaneous way of administration. Natalizumab also showed promising results in terms of efficacy but its safety is still under investigation. To date no particular advances have been recently appeared in the literature concerning conventional immunosuppressive drugs. Surgery remains a valid resort for refractory patients. Autologous stem cell transplantation represents a new hope as rescue treatment for patients with severe refractory Crohn's disease.     

Azathioprine or 6-mercaptopurine for inflammatory bowel disease: do risks outweigh benefits?

The treatment of Crohn's disease and ulcerative colitis has evolved and has improved the quality of life of patients afflicted with these disorders. Immune modulators such as azathioprine and 6-mercaptopurine are an important class of medications used for the treatment of patients with inflammatory bowel disease. Controlled studies have demonstrated their efficacy in both induction and maintenance of remission in Crohn's disease, and similarly, for the induction and maintenance of remission in patients with ulcerative colitis. These agents have had an increasing importance in the management of steroid-resistant, steroid-dependent diseases, and fistulizing Crohn's disease. The primary limitations to these agents have been their slow onset of action and their side effect profile. Despite these limitations, these agents have demonstrated efficacy and have become paramount to the management of patients with these incurable potentially disabling disorders. The precise role of azathioprine/6-mercaptopurine, their limitations and their safety are reviewed in this paper.     

Predictors of response to infliximab in patients with fistulizing Crohn's disease.

OBJECTIVE: To evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn's disease. METHODS: Consecutive patients with fistulizing Crohn's disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. RESULTS: 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (%) rates (partial/complete) depending on fistula location were: enterocutaneous (25/68%), perianal (35/60%), rectovaginal (36/64%), and enterovesical (20/40%). None of the studied variables (including concomitant immunosuppressive therapy) correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21%) depending on the dose of infliximab was: first dose (5.6%), second (7.4%), and third (11.1%). CONCLUSIONS: Infliximab is an efficacious treatment for fistulizing Crohn's disease. Partial response was achieved in approximately one third of the patients, and complete response in more than half. No studied variable was predictive of response. Adverse effects were relatively infrequent and mild.     

Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease

OBJECTIVES: Tumor necrosis factor-alpha plays a central role in chronic intestinal inflammation of Crohn's disease. Targeting this cytokine with the chimeric monoclonal antibody infliximab has emerged as an effective form of therapy in adult Crohn's disease patients. We sought to determine whether infliximab treatment would benefit pediatric patients with medically refractory Crohn's disease. We also assessed the duration of response, comparing children with early disease to children with long-standing (late) Crohn's disease. METHODS: Fifteen consecutive children (mean age 12.8 +/- 3.2 yr) with medically refractory Crohn's disease were enrolled in a prospective, open-label trial of a single, 5-mg/kg infliximab intravenous infusion. Medically refractory disease was defined as an inability to taper steroids, lack of response to immunomodulator therapy over 4 months, and active disease as measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Primary endpoints included measurements of disease activity (PCDAI), steroid use, and duration of clinical response. RESULTS: In all, 14/15 children (94%) improved after infliximab infusion, with a significant decrease of both PCDAI and daily steroid use by 4 wk. Ten patients (67%) achieved complete remission by 10 wk. Among the 14 patients who responded, three of six children (50%) with early disease maintained clinical response through the 12-month trial period, compared to none of eight children with late disease. There were no serious complications associated with the use of infliximab in any of the patients. CONCLUSIONS: Infliximab is safe and effective in the short-term treatment of medically refractory pediatric Crohn's disease. More importantly, there is a remarkably prolonged duration of response after infliximab therapy in children with early compared to late Crohn's disease.     

Inflammatory bowel disease: current therapeutic options

Medical management of inflammatory bowel diseases (IBD) includes two treatment strategies: induction and maintenance of remission. 5-Aminosalicylates are mostly used for mild active IBD and for maintenance treatment in ulcerative colitis (UC). Glucocorticoids remain, despite their frequent (and occasionally severe) side effects, as the mainstay for induction of remission in moderate to severe active IBD, both UC and Crohn's disease (CD). Cyclosporine and infliximab have emerged as the main, rapid-acting, alternatives in steroid-refractory UC and CD, respectively. Thiopurines (azathioprine and 6-mercaptopurine) are the most efficient and used immunomodulators in IBD; steroid refractoriness, steroid dependency, and long-term maintenance of remission for both UC and CD are their main indications. Methotrexate and infliximab may be used in the same clinical settings as thiopurines in CD, but not in UC; however, these drugs are a second-line treatment because of safety profile and economic costs.