Hepatosplenic T-Cell Lymphoma: A Population-Based Study Assessing Incidence and Association With Immune-Mediated Disease.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare malignancy of unknown incidence that has been associated with immune-mediated disease. This study explored the incidence and patient characteristics of HSTCL in a population of 15.5 million over a 13-year period using a comprehensive national pathology database in The Netherlands (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief) with 100% capture. Twelve cases of HSTCL were identified during this period. The overall incidence of HSTCL in the Dutch population over this period was estimated at 0.06 per million inhabitant-years. All but 2 of the patients were adults at the time of diagnosis (median age, 34.5 years), and most patients died within a year of diagnosis. Three patients had a history of immune-mediated disease, 1 of whom was receiving azathioprine at the time of HSTCL diagnosis. Azathioprine as well as anti-tumor necrosis factor-α agents have been reported as possibly being associated with HSTCL. None of the 12 HSTCL patients had been treated with an anti-tumor necrosis factor-α agent.

Drug therapies and the risk of malignancy in Crohn's disease: results from the TREAT™ Registry.

OBJECTIVES: We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined. METHODS: Utilizing data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT™) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, influences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95 % confidence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA). RESULTS: As of 23 February 2010, 6,273 CD patients (infliximab during registry=3,420 (during or within 1 year before registry=3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab- and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR)=1.59/10 years; P<0.001), disease duration (HR=1.64/10 years; P=0.012), and smoking (HR=1.38; P=0.045) but neither immunosuppressive therapy alone (HR=1.43; P=0.11), infliximab therapy alone (HR=0.59; P=0.16), nor their combination (HR=1.22, P=0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio=4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither. CONCLUSIONS: In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.

Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial.

BACKGROUND: Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment. OBJECTIVE: To carry out a post hoc analysis of A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I (ACCENT I) to evaluate the association between serum infliximab trough levels and C-reactive protein (CRP) after 14 weeks of induction treatment with durable sustained long-term response (Crohn's Disease Activity Index decrease ≥70 points and reduction ≥25% from baseline). DESIGN: ACCENT I was a multicentre, randomised, placebo-controlled study. Week 14 trough levels and CRP percentage decrease from baseline to week 14 were compared between patients with and without durable sustained response through week 54. Sensitivity and specificity were determined to predict durable sustained response. Receiver operating characteristic (ROC) curves identified optimal cut-off points; logistic regression determined ORs. RESULTS: After induction with 5 mg/kg infliximab, 25% (37/147) and 33% (47/144) of patients sustained week 14 response to infliximab 5 or 10 mg/kg, respectively, administered every 8 weeks without dose escalation, through week 54. Median week 14 trough levels of patients with and without durable sustained response to infliximab 5 mg/kg were 4.0 and 1.9 µg/mL, respectively (p=0.0331). Optimal predictors of durable sustained response to maintenance infliximab 5 mg/kg were week 14 trough level ≥3.5 µg/mL and ≥60% CRP decrease (ORs (95% CI), 3.5 (1.1 to 11.4) and 7.3 (1.4 to 36.7)), respectively, in patients with raised baseline CRP (>8.0 mg/L); area under the ROC curve was 0.75 for both predictors. A ≥3.5 µg/mL week 14 infliximab serum level did not predict durable sustained response to 10 mg/kg maintenance infliximab. CONCLUSIONS: Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher postinduction trough levels than patients without durable sustained response. Serum infliximab trough levels ≥3.5 µg/mL and ≥60% CRP decrease were significantly associated with durable sustained response.

Validation of endoscopic activity scores in patients with Crohn's disease based on a post hoc analysis of data from SONIC.

BACKGROUND & AIMS: Mucosal healing might alter midterm and long-term outcomes of patients with Crohn's disease (CD) and has become an important end point in clinical trials. However, the minimal degree of mucosal improvement (endoscopic response) required to alter midterm outcomes is not known. We aimed to determine the best definition of endoscopic response by evaluating data on the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Crohn's Disease Endoscopic Index of Severity (CDEIS) from the Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease (SONIC trial). METHODS: We analyzed data from 172 patients who participated in the SONIC trial, were found to have endoscopic lesions at baseline, and underwent a second endoscopic examination at week 26 of treatment with infliximab, azathioprine, or both. Mucosal healing was defined as absence of ulcers. A central reader calculated SES-CD and CDEIS results. Different cutoff values were set for endoscopic response based on the SES-CD or CDEIS. The diagnostic ability of these different cutoff values was evaluated using receiver operating characteristic (ROC) curves, positive likelihood ratios (PLR), and negative likelihood ratios (NLR). Corticosteroid-free clinical remission (CFREM) at week 50 was used as a binary classifier. RESULTS: Based on analyses of ROC curves, PLR, and NLR, endoscopic response was defined as a decrease from baseline in SES-CD of at least 50%. At week 26, mucosal healing and endoscopic response were achieved in 48% and 65% of patients, respectively. Mucosal healing at week 26 was associated with CFREM at week 50, with 56% sensitivity, 65% specificity, a PLR of 1.60, and an NLR of 0.67. Endoscopic response at week 26 was associated with CFREM at week 50, with 74% sensitivity, 48% specificity, a PLR of 1.42, and an NLR of 0.54. Endoscopic response, defined as a decrease from baseline in CDEIS of at least 50%, yielded similar results. CONCLUSIONS: In patients with CD, mucosal healing and endoscopic response (defined as a decrease from baseline in SES-CD or CDEIS of at least 50%) at week 26 of treatment identified those most likely to be in CFREM at week 50. The ability of the proposed endoscopic response cutoff value to predict midterm CFREM should be validated in an independent, prospective cohort. Its correlation with changes in long-term disease progression still needs to be demonstration. ClinicalTrials.gov, Number: NCT00094458.

Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry.

OBJECTIVES: The objective of this study was to contribute long-term safety data for infliximab and other therapies in Crohn's disease (CD). METHODS: We prospectively evaluated CD patients enrolled in the large, observational Crohn's Therapy, Resource, Evaluation, and Assessment Tool registry, established to compare infliximab safety with conventional nonbiological medications in CD. RESULTS: A total of 6,273 patients were enrolled and evaluated on or before 23 February 2010; 3,420 received infliximab (17,712 patient-years; 89.9% received ≥ 2 infusions) and 2,853 received other-treatments-only (13,251 patient-years). Mean length of patient follow-up was 5.2 years. More infliximab- than other-treatments-only-treated patients had moderate-to-severe (30.6% vs. 10.7%) or severe-to-fulminant (2.5% vs. 0.6%) disease severity (P < 0.001). In the year before enrollment, more infliximab- than other-treatments-only-treated patients required surgical intervention (17.4% vs. 13.6%), medical hospitalization (14.2% vs. 8.8%), prednisone (47.8% vs. 31.4%), immunomodulators (52.0% vs. 32.1%), and narcotic analgesics (17.3% vs. 9.1%). Patient mortality was similar for infliximab- and other-treatments-only-treated patients (0.58 vs. 0.59/100 patient-years). In multivariate logistic regression analyses, treatment with prednisone (hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.55, 2.95; P < 0.001) or narcotic analgesics (HR = 1.79, 95% CI = 1.29, 2.48; P < 0.001) and age (HR = 1.08, 95% CI = 1.07, 1.09; P < 0.001) were associated with increased mortality risk. Neither infliximab nor immunomodulator treatment was associated with increased mortality risk. Factors independently associated with serious infections included moderate-to-severe disease activity (HR = 2.24, 95% CI = 1.57, 3.19; P < 0.001), narcotic analgesic treatment (HR = 1.98, 95% CI = 1.44, 2.73; P < 0.001), prednisone therapy (HR = 1.57, 95% CI = 1.17, 2.10; P = 0.002), and infliximab treatment (HR = 1.43, 95% CI = 1.11, 1.84; P = 0.006). CONCLUSIONS: Mortality was similar between infliximab- and other-treatments-only-treated CD patients. An increased risk of serious infection with infliximab was observed, although CD severity and use of prednisone or narcotic analgesics carried higher risks.

A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease.

OBJECTIVES: The objective of this study was to analyze the safety of long-term infliximab treatment, with/without concomitant immunomodulators, across Crohn's disease (CD) and ulcerative colitis (UC) clinical trials. METHODS: To maximize sample size, we pooled primary safety data across 10 CD or UC trials, including five randomized, controlled trials contributing data from patients who received intravenous infliximab 5 or 10 mg/kg (n=1,713; ±azathioprine) or placebo (n=406; ±azathioprine). Pooled incidences and 95% confidence intervals (CIs) were determined for mortality, infection, and malignancy. Standardized incidence ratios and 95% CIs were also determined for malignancies using the Surveillance, Epidemiology, and End Results database. RESULTS: We observed no increase in infections, serious infections, or malignancy with infliximab vs. placebo in these patients with inflammatory bowel disease (IBD). In patients with UC, but not CD, immunomodulator treatment (vs. treatment without immunomodulator) yielded a higher incidence (95% CI) of infections (120.07 (110.66, 130.08)/100 patient-years (pt-yrs) vs. 92.47 (84.54, 100.94)/100 pt-yrs). Among placebo-treated patients with CD, but not UC, those with immunomodulator use demonstrated a higher incidence (95% CI) of malignancy vs. no immunomodulator treatment (1.84 (0.22, 6.66)/100 pt-yrs vs. 0.00 (0.00, 0.00)/100 pt-yrs). Mortality and infection-related mortality appeared unaffected by infliximab or immunomodulator treatment. CONCLUSIONS: Infliximab treatment of IBD did not appear to affect incidences of infection, mortality, or malignancy. Relative to patients with no immunomodulator use, immunomodulator-treated UC patients demonstrated a higher incidence of infection and immunomodulator-plus-placebo-treated CD patients demonstrated a higher incidence of malignancy.

A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and usually fatal lymphoma that primarily affects men younger than 35 years old. Treatment of patients with inflammatory bowel disease (IBD) using antibodies to tumor necrosis factor (anti-TNFs) and thiopurines has been associated with HSTCL. We investigated the medications, duration of therapy, and ages of patients associated with HSTCL. METHODS: We collected and analyzed data on the association between HSTCL, and anti-TNF and thiopurine therapies in patients with IBD from published reports and the MedWatch reporting system of the US Food and Drug Administration. RESULTS: Of 36 patients with HSTCL, 20 received therapy with infliximab and a thiopurine and 16 received a thiopurine as monotherapy for IBD. Four patients who had been treated with infliximab and a thiopurine also received adalimumab. One of these patients had been given infliximab, adalimumab, and natalizumab. Of 31 patients of known gender, only 2 were female. Twenty-seven of the 30 patients of known age were younger than 35 years old. CONCLUSIONS: Most patients with HSTCL who received long-term therapy (at least 2 y) with thiopurines for IBD were men younger than 35 years old. There were no reported cases of HSTCL in patients with IBD who received only anti-TNF therapy. Physicians should consider giving thiopurines and anti-TNF agents to young male patients with IBD only in cases in which a clear benefit is expected, such as in early stage disease in untreated patients or possibly in very severe cases.

Infliximab, azathioprine, or combination therapy for Crohn's disease.

BACKGROUND: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown. METHODS: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50. RESULTS: Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group. CONCLUSIONS: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)

A multicenter retrospective experience of infliximab in Crohn's disease patients: infusion reaction rates and treatment persistency.

BACKGROUND: Infusion reactions have been associated with infliximab therapy, but no study has assessed how physicians treat and manage this common adverse event. GOALS: To determine how gastroenterologists manage infusion reactions, identify prophylactic pretreatment protocols, and determine infliximab treatment persistence in the presence of infusion reactions. METHOD: This retrospective multicenter chart review analyzed data from adults younger than 90 years at the time of their first infliximab infusion from 9 academic or community-based gastroenterology practices. Infusion reaction rates were compared using a Chi-square test with Yates' correction. Kaplan-Meier methods assessed infliximab treatment persistency. RESULTS: Among 6,468 infusions with known infusion reaction status administered to 447 patients, 3.5% (226/6,468) of infusions resulted in an infusion reaction, and less than 0.1% (2/6,468) were associated with a serious infusion reaction. Among all patients, 19.7% (88/447) experienced at least 1 infusion reaction, whereas 0.4% (2/447) experienced a serious infusion reaction. Patients receiving concomitant immunosuppressives had fewer infusion reactions compared to patients not receiving them (57/322 patients, 17.7% vs 31/125 patients, 24.8%; P=.118). The cumulative proportion of patients continuing infliximab therapy at 2, 4, and 5 years was 73%, 58%, and 54%, respectively. CONCLUSIONS: The incidence of serious infusion reactions was low. In the overall experience observed in this clinical practice retrospective cohort, no conclusions can be drawn regarding the effectiveness of specific infusion reaction prophylactic measures. In spite of infusion reactions, the long-term infliximab treatment persistence rate was high.

Quality of life after proctocolectomy with ileoanal anastomosis for patients with ulcerative colitis.

Ulcerative colitis, a chronic inflammatory disease of the rectal and colonic mucosa, affects approximately 250,000 to 500,000 people in the United States, with 30% to 40% of patients requiring some form of surgical intervention during the course of their disease. The predominant reason for total proctocolectomy is for symptoms refractory to currently available medical therapy. Less common reasons are dysplasia or cancer. The goal of colectomy is to prevent recurrence of systemic inflammatory disease. Consequently, surgery with total proctocolectomy and creation of an ileal J-pouch-anal anastomosis has become the procedure of choice for many patients without other therapeutic options. Health-related quality of life (QOL) in patients with severe ulcerative colitis is so poor that, after ileal J-pouch-anal anastomosis, QOL is considered to improve in most clinical studies (8 studies, improved QOL; 1 study, no change; 1 study, QOL worse than general population). However, QOL and bowel function after such surgery cannot be considered "normal" in all patients, because a substantial number still have problems with urgency, leakage, nocturnal soiling, sexual dysfunction, and pouchitis, and some require conversion to a permanent ileostomy after ileal J-pouch-anal anastomosis failure. Thus, despite the availability of ileal J-pouch-anal anastomosis, surgery does not always restore all aspects of QOL to normal.

Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry.

BACKGROUND & AIMS: Long-term safety data for infliximab and other therapies in Crohn's disease (CD) are needed. METHODS: We prospectively evaluated patients for prespecified safety-related outcomes. RESULTS: As of August 2004, 6290 patients were enrolled; 3179 received infliximab (5519 patient-years), 87% of whom received at least 2 infusions, and 3111 received other therapies (6123 patient-years). The mean length of follow-up evaluation was 1.9 years. More infliximab-treated patients had moderate-to-severe (30.8% vs 10.3%) or severe-fulminant (2.5% vs .6%) CD, and had surgical (17.5% vs 13.8%) or medical (14.4% vs 9.1%) hospitalizations in the previous year. More patients were taking prednisone (27.4% vs 16.1%), immunomodulators (49.4% vs 32.2%), or narcotic analgesics (9.8% vs 5.4%) when compared with those receiving other therapies (P<.001, all comparisons). The mortality rates were similar for infliximab- and non-infliximab-treated patients (.53 per 100 patient-years vs .43; relative risk, 1.24; 95% confidence interval [CI], .73-2.10). In multivariate logistic regression analysis, only prednisone was associated with an increased mortality risk (odds ratio [OR], 2.10; 95% CI, 1.15-3.83; P=.016). Although the unadjusted analysis showed an increased risk for infection with infliximab use, multivariate logistic regression analysis suggested that infliximab was not an independent predictor of serious infections (OR, .99; 95% CI, .64-1.54). Factors independently associated with serious infections included prednisone use (OR, 2.21; 95% CI, 1.46-3.34; P<.001), narcotic analgesic use (OR, 2.38; 95% CI, 1.56-3.63; P<.001), and moderate-to-severe disease activity (OR, 2.11; 95% CI, 1.10-4.05; P=.024). CONCLUSIONS: Mortality rates were similar between infliximab- and non-infliximab-treated patients. The increased risk for serious infection observed with infliximab likely was owing to disease severity and prednisone use.

Factors associated with the development of intestinal strictures or obstructions in patients with Crohn's disease.

OBJECTIVE: Theoretical concern exists that rapid luminal healing in Crohn's disease (CD) with therapies like infliximab increases the risk of intestinal stenosis, stricture, or obstruction (SSOs). METHODS: Data were analyzed from the ongoing observational TREAT (the Crohn's Therapy, Resource, Evaluation, and Assessment Tool) Registry and ACCENT I (A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen) study. Investigators reported SSOs as adverse events or serious adverse events. RESULTS: In TREAT, SSOs occurred at a significantly higher rate in patients treated with infliximab compared with patients who received other treatments only (1.95 events/100 patient-years vs 0.99 events/100 patient-years; p < 0.001). Using multivariable analyses, however, infliximab therapy was not associated with SSO development. CD severity at the time of event onset (hazard ratio (HR) = 2.35, 95% confidence internal (CI) 1.35-4.09); CD duration (HR = 1.02, 95% CI 1.00-1.04); ileal disease (HR = 1.56, 95% CI 1.04-2.36); and new corticosteroid use (HR = 2.85, 95% CI 1.23-6.57) were associated with SSOs. In ACCENT I, no increase in SSOs was reported in patients who received infliximab maintenance therapy compared with those who received episodic therapy, despite higher median cumulative infliximab exposure. Additionally, there was no increase in SSO development with rapid mucosal healing (healing at week 10). CONCLUSIONS: Although unadjusted analyses suggested that patients who received infliximab were twice as likely to develop SSOs, multivariable analysis adjusting for other factors demonstrated that only disease duration, disease severity, ileal disease, and new corticosteroid use were significantly associated with SSO development.

Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease.

BACKGROUND: The endoscopic substudy of the ACCENT I (A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen) Crohn's disease trial examined the effects of infliximab on mucosal inflammation and mucosal healing, and assessed their impact on outcomes. DESIGN: ACCENT I was a randomized, double-blind, parallel group study. SETTING: This study took place at multiple centers in North America, Europe, and Israel. MAIN OUTCOME MEASUREMENTS: Ileocolonoscopic examinations were performed at weeks 0, 10, and 54. Complete mucosal healing was defined as the absence of all mucosal ulcerations. The end point of principal interest was the proportion of patients randomized as responders with mucosal healing at week 10. The proportion of responders who demonstrated mucosal healing at week 54 or at both weeks 10 and 54 is also summarized. Changes in Crohn's disease endoscopic index of severity (CDEIS) scores from baseline to week 10 and 54 were calculated for all patients in this substudy. RESULTS: Complete mucosal healing by week 10 occurred in significantly more week 2 responders who had received 3 doses of infliximab compared with a single dose (31% vs. 0%, p = 0.010). A significantly higher proportion of week 2 responders in the combined scheduled maintenance group had complete mucosal healing at week 54 compared with the episodic group (50% vs. 7%, p = 0.007). The results for all patients are consistent with those for week 2 responders only. Significantly greater improvement in the CDEIS occurred with scheduled maintenance compared with episodic treatment at week 10 (p

Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease.

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.