首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到10条相似文献,搜索用时 218 毫秒
1.
OBJECTIVE: The aim of this study was to assess the efficacy and safety of a single infusion of infliximab in the treatment of pediatric Crohn's disease (CD). METHODS: A total of 21 pediatric CD patients were enrolled at seven study centers and randomized to receive a single infusion of infliximab 1 mg/kg (n = 6), 5 mg/kg (n = 7), or 10 mg/kg (n = 8) over at least 2 hrs at week 0 in this multicenter, open-label, dose-blinded trial. Efficacy assessments, including the Pediatric Crohn's Disease Activity Index (PCDAI), modified CDAI, C-reactive protein concentration (CRP), and erythrocyte sedimentation rate (ESR) determinations, were made at screening and at weeks 1, 2, 4, 8, and 12. Adverse events were assessed throughout study participation. RESULTS: Improvements in the PCDAI, modified CDAI, ESR, and CRP were observed with all infliximab doses, beginning at week 1. On average, all treated patients experienced approximately 50% improvement in the PCDAI by week 2. By week 12, the PCDAI remained approximately 30% improved from baseline. During the study, all 21 patients (100%) achieved a clinical response, and 10 patients (48%) achieved clinical remission. There were no infusion reactions in any of the treatment arms. CONCLUSIONS: The results of this trial suggest that infliximab may be safe and effective as short-term therapy of medically refractory moderate to severe CD in a pediatric population.  相似文献   

2.
BACKGROUND: We assessed the tolerability and clinical benefit of adalimumab, a human antibody to tumor necrosis factor (TNF), in patients with Crohn's disease who had previously received and responded to the chimeric anti-TNF antibody infliximab, but who no longer had a sustained response and/or tolerance to infliximab. METHODS: A total of 24 patients with Crohn's disease who had lost responsiveness or developed intolerance (acute or delayed infusion reactions) to infliximab were enrolled in a 12-wk uncontrolled trial and treated with subcutaneous adalimumab 80 mg at week 0 and then 40 mg every other week starting at week 2. After week 4, the dose could be escalated to 40 mg weekly in patients who did not achieve clinical remission, complete fistula closure, and complete steroid withdrawal. Outcome measures included the ability to tolerate adalimumab and clinical remission (defined as a Crohn's disease activity index (CDAI) score < or =150 points) and clinical response (defined as a decrease in the CDAI) > or =100 points) in patients who had a baseline CDAI score > or =220. RESULTS: None of the patients experienced acute or delayed hypersensitivity reactions during treatment with adalimumab (including 14 who previously experienced treatment-limiting acute hypersensitivity reactions and 6 who previously experienced delayed hypersensitivity reactions with infliximab). Of 17 patients with baseline CDAI scores > or =220: clinical remission occurred at weeks 4 and 12 in 2 (12%) and 5 (29%), respectively; and clinical response occurred in 7 (41%) and 10 (59%), respectively. Nineteen patients (79%) escalated their dose during weeks 4-6. CONCLUSIONS: Adalimumab is well tolerated and appears to be a clinically beneficial option for patients with Crohn's disease who have previously lost their response to, or cannot tolerate infliximab.  相似文献   

3.
BACKGROUND & AIMS: The effect of different treatment regimens on antibody responses to infliximab and their clinical significance was examined by using data from ACCENT I. METHODS: Patients with Crohn's disease (n = 573) received 5 mg/kg infliximab (week 0) and then were randomly assigned to blinded infusions at weeks 2 and 6 and every 8 weeks until week 46 of placebo (group I), 5 mg/kg infliximab (group II), or 5 mg/kg infliximab at weeks 2 and 6, followed by 10 mg/kg thereafter (group III). At week 14 or later, patients losing response could cross over to episodic infliximab treatment increased by 5 mg/kg. Samples for antibody determination were collected before the first infusion and at weeks 14, 22, 54, 62, 72, and, if applicable, before and after crossover. RESULTS: Through week 72, antibodies to infliximab were detected in 30%, 10%, and 7% of groups I, II, and III, respectively (P < 0.0001). Patients receiving immunomodulators had a lower incidence of antibodies compared with patients receiving infliximab alone (10% and 18%, respectively; P = 0.02). Antibodies were associated with a 12% absolute increase in infusion reactions but no increase in serious infusion reactions or serum sickness-like reactions. In the overall population, similar proportions of antibody-positive and antibody-negative patients achieved clinical response (64% and 62%, respectively; P = NS) or clinical remission (41% and 39%, respectively; P = NS) at week 54. Notably, 86% of patients responded to retreatment, and 63% were in clinical response at week 54; however, fewer antibody-positive group I patients attained clinical remission (31%) compared with those who were antibody negative (37%) or antibody inconclusive (54%) (P = NS). CONCLUSIONS: Reduced antibody formation and greater clinical benefit were observed with an induction regimen followed by maintenance treatment compared with a single dose followed by episodic retreatment in Crohn's disease patients treated with infliximab.  相似文献   

4.
BACKGROUND & AIMS: The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine (AZA) or 6-mercaptopurine (6-MP) in steroid-dependent Crohn's disease patients. METHODS: Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows: the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months, and the naive stratum consisted of patients not treated previously with AZA/6-MP. Patients were randomized to infliximab 5 mg/kg or placebo at weeks 0, 2, and 6. All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study. The primary end point was remission off steroids at week 24. RESULTS: Among the 113 enrolled patients (55 in the failure stratum), 57 were assigned to infliximab. At week 24, the success rate (intent-to-treat analysis) was higher in the infliximab group than in the placebo group (57% vs 29%; P = .003); at weeks 12 and 52, the corresponding rates were 75% vs 38% (P < .001) and 40% vs 22% (P = .04), respectively. In each stratum, the success rate was significantly higher in the infliximab group at weeks 12 and 24, and a trend was found at week 52. In the failure stratum, only 27% of the patients in the infliximab group were still in remission off steroids, compared with 52% in the naive stratum. Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group. CONCLUSIONS: Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn's disease patients.  相似文献   

5.
BACKGROUND & AIMS: This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). METHODS: Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index > or =70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score <150) at weeks 26 and 56. RESULTS: The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). CONCLUSIONS: Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.  相似文献   

6.
BACKGROUND & AIMS: This analysis of Crohn's disease patients treated with infliximab in ACCENT I compared episodic and scheduled treatment strategies under conditions that simulate clinical practice. METHODS: After 5 mg/kg infliximab at week 0, 573 patients were randomized to infusions at weeks 2 and 6 and every 8 weeks until week 46 of placebo (episodic), infliximab 5 mg/kg at weeks 2 and 6 followed by 5 mg/kg (5 mg/kg scheduled) every 8 weeks, or infliximab 5 mg/kg at weeks 2 and 6 followed by 10 mg/kg (10 mg/kg scheduled) every 8 weeks. At or after week 14, treatment could be given with a dose of infliximab 5 mg/kg higher upon loss of response. RESULTS: The efficacy of scheduled infliximab therapy was better than episodic treatment. Crohn's Disease Activity Index (CDAI) scores were consistently significantly better in the 10 mg/kg scheduled maintenance group from weeks 10 to 54, and response and remission rates (combined scheduled) were significantly higher from weeks 10 to 30. A greater proportion of patients achieved complete mucosal healing at week 54 (P = 0.041). A lower proportion developed antibodies to infliximab in the scheduled groups than in the episodic group (9% [5 mg/kg], 6% [10 mg/kg], 28% [episodic], respectively). Scheduled strategy patients had fewer Crohn's disease-related hospitalizations (P = 0.014) and surgeries (P = 0.01) than episodic strategy patients. CONCLUSIONS: The scheduled infliximab groups, particularly the 10 mg/kg group, had better CDAI and Inflammatory Bowel Disease Questionnaire (IBDQ) responses than those in the episodic group. Both scheduled groups had fewer hospitalizations, higher rates of mucosal healing, and fewer developed antibodies than those in the episodic group, with no increase in side effects.  相似文献   

7.
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.  相似文献   

8.
BACKGROUND: Infliximab has recently emerged as an efficacious agent for patients with severe Crohn's disease. There are only few studies on the use of infliximab in children with Crohn's disease: most of them are retrospective and deal only with the clinical response to the drug. AIM: We aimed at assessing the efficacy of infliximab in children and adolescents with severe Crohn's disease recruited consecutively and followed up prospectively at a single centre. Clinical response, intestinal inflammation and growth pattern were evaluated. PATIENTS: Eighteen patients entered into the trial (median age: 13 years, range: 6-18). They were referred because of severe symptoms with unsatisfactory response to conventional drugs. METHODS: All patients received a baseline schedule of three intravenous infusions of infliximab (0, 2 and 6 weeks), 5 mg/kg. Paediatric Crohn's Disease Activity Index, nutritional and activity serum variables, and ileocolonoscopy (with histology) were evaluated before and 8 weeks after beginning the therapy. All patients had long-term administration of azathioprine (2 mg/kg per day). After the baseline schedule, eight patients had a retreatment infusion of infliximab (5 mg/kg) every 8 weeks. Weight and height Z scores were measured before starting the baseline infusion programme and after 6 months. RESULTS: After 8 weeks of therapy, there was a dramatic improvement in Paediatric Crohn's Disease Activity Index, in nutritional and activity blood parameters, as well as in endoscopic and histological scores; 10 patients had a clinical remission (Paediatric Crohn's Disease Activity Index < or = 10), 12 patients had an inflammatory remission (decrease in both endoscopic and histological scores for > or = 50% as compared to baseline values). In all patients corticosteroids were stopped within 4 weeks after beginning infliximab therapy. After 6 months of therapy, Paediatric Crohn's Disease Activity Index was markedly lower than the pre-treatment value; however, it was significantly lower in patients on retreatment than in those who received only three infusions of infliximab. Furthermore, a significant increase in both weight and height Z scores was observed 6 months after beginning of the baseline infusion programme. Moreover, weight and height gain was significantly higher in patients on retreatment rather than in those treated only with three baseline infusions of infliximab. Mild infusion reactions controlled by slowing infusion rate were observed in four patients. No delayed hypersensitivity-like reactions were seen. CONCLUSIONS: In children with severe Crohn's disease, infliximab is a safe and valuable treatment in inducing remission, in healing inflammatory lesions of the gut, as documented by endoscopy and histology, and in promoting growth. Retreatment infusions of infliximab may be suggested in childhood-onset Crohn's disease to maintain remission and reverse growth failure.  相似文献   

9.
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.  相似文献   

10.
英夫力西单抗治疗难治性溃疡性结肠炎   总被引:1,自引:0,他引:1  
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。  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号