Variations in Insurance Policies Regarding Adherence to the AGA Guideline for Therapeutic Drug Monitoring in IBD.

BACKGROUND: The American Gastroenterological Association (AGA) published guidelines on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) in August 2017 recommending use of reactive TDM to guide treatment changes in patients with active IBD who are being treated with anti-tumor necrosis factor (anti-TNF) agents or thiopurines. We sought to determine if changes in national clinical practice guidelines result in changes in health care insurance policies within 6 months of publication. METHODS: Using the National Association of Insurance Commissioners Market Share Reports of the top 125 insurance companies by market share in 2016, we reviewed the largest 50 companies for their publicly available online policies regarding TDM of anti-TNF and thiopurine in IBD. For those with available policies, we looked for whether proactive and/or reactive TDM was covered. Policies were also looked for genetic or enzymatic activity of thiopurine methyltransferase (TPMT) testing before use of thiopurine. All these policies were reviewed within the week of publication of the AGA guideline. They were reviewed again 1, 3, and 6 months later for evaluation of any policy changes after the published AGA guidelines. RESULTS: Fifty of the largest insurance company policies were included. With regards to TDM policy for anti-TNF, we did not find a difference between baseline and 6 months values (P=0.38). With regards to TDM policy for thiopurine, we did not find a difference between baseline and 6 months values (P=1.00). About half of the companies did not have a policy regarding TPMT testing for thiopurine use. Of those with available policies for TPMT testing, there was no difference between baseline and 6 months values (P=0.13). CONCLUSIONS: Even after publication of national guidelines, a large number of the largest health insurance companies do not have a policy regarding reactive TDM for anti-TNF and/or thiopurines. Majority of those with a policy, fail to meet the current standards set forth by the practice guidelines. A significant gap remains between the insurance policies and AGA guidelines. Further studies are needed to determine how to effectuate change to improve insurance company adherence to clinical practice guidelines.

Effect of Consent and Educational Adjuncts to Consent on Patient Perceptions About Colonoscopy.

BACKGROUND AND AIMS: Informed consent is a vital preprocedural step for endoscopy but there are substantial variations in its delivery. We therefore sought to assess a multifaceted intervention to improve the consent process. METHODS: Gastroenterologists at a tertiary center were educated on the recommended components of informed consent. Following this, 3 cohorts of patients undergoing colonoscopy were surveyed before and after consent. In one cohort, the effect of optimized verbal consent alone was assessed. In the second and third groups, the effects of the addition of either a handout or a video describing colonoscopy and its risks were evaluated. The primary outcomes were the changes between preconsent and postconsent survey responses regarding confidence in understanding the procedure's purpose, likelihood of adverse events, and levels of anxiety. RESULTS: In total, 240 patients were included with 79 to 81 patients per group. There were no significant differences among the groups' survey responses. Compared with patients receiving verbal consent alone, fewer patients in the handout and video groups increased their perceived risk of adverse events following consent, but this difference did not reach significance (P=0.08). Examining all groups together, anxiety levels changed significantly after consent (P=0.003), with 31% of patients reducing their anxiety level, 8% increasing it, and 62% having no change. CONCLUSIONS: The consent process appears to decrease patient anxiety about colonoscopy. When used in conjunction with a high-quality verbal consent, written or video educational adjuncts provided on the day of colonoscopy likely have no effect on patient perceptions.

A National Survey of the Prevalence and Impact of Cytomegalovirus Infection Among Hospitalized Patients With Ulcerative Colitis.

GOALS: To estimate the effect of cytomegalovirus (CMV) in patients with ulcerative colitis (UC), and compare these outcomes to patients with CMV without UC. BACKGROUND: The impact of CMV infection in UC is not well understood. STUDY: We analyzed records from the Nationwide Inpatient Sample (NIS) of patients with UC and CMV between 2006 and 2012. Differences in outcomes were determined between patients with UC and CMV and those with UC without CMV. Secondary analysis compared outcomes of patients with UC and CMV to patients with CMV alone. RESULTS: Patients with UC and CMV (n=145) had longer length of stay (16.31 vs. 5.52 d, P<0.0001), higher total charges ($111,835.50 vs. $39.895, P=0.001), and were less likely to be discharged home without services (50.0% vs. 81.83%, P<0.0001) compared with patients with UC without CMV (n=32,290). On regression analysis, CMV was significantly associated with higher total charges (P<0.01) and longer length of stay (P<0.01), but not for increased need for colorectal surgery. When comparing patients with UC and CMV to patients with CMV alone (n=14,960), patients with CMV alone had a higher Charlson Comorbidity Index and a trend toward higher in-hospital mortality. CONCLUSIONS: CMV infection in hospitalized patients with UC is associated with a longer length of stay, increased total charges, and fewer routine discharges, but not increased surgery or mortality. Patients with CMV alone had the worst outcomes of all groups suggesting that CMV in UC patients may not have the same negative impact as in other diseases.

Biologics and immunomodulators for treating Crohn's disease developing after surgery for an initial diagnosis of ulcerative colitis: a review of current literature.

Crohn's Disease (CD) or CD-like (CDL) conditions of the pouch are rare long-term inflammatory complications of patients who were initially diagnosed with ulcerative colitis (UC) who undergo total proctocolectomy with ileo-anal anastomosis (IPAA). There are no societal guidelines nor a consensus on their treatment, resulting in significant challenges for clinicians for their diagnosis and management. It is important to differentiate them from other more common pouch-related complications like pouchitis, cuffitis, irritable pouch syndrome, surgery associated stricture, and fistula. In this review, we focus on the less common presentation of CD and CDL conditions of the pouch and their treatment with the use of anti-TNF therapy with or without immunomodulator.

Mortality Is Rare Following Elective and Non-elective Surgery for Ulcerative Colitis, but Mild Postoperative Complications Are Common.

BACKGROUND DATA: Currently, data regarding the rates of morbidity and mortality following non-elective colectomy for ulcerative colitis (UC) are variable. We sought to determine the rates and predictors of 90-day mortality and complications following colectomy for UC. METHODS: Patients undergoing an initial surgery for UC at a tertiary care center between January 2002 and January 2014 were included. Patients were identified using ICD-9 code 556.x. Each record was manually reviewed for demographic information, medical histories, UC history, medications, and data regarding the admission and discharge. Charts were reviewed for mortality and complications within 90 days of surgery. Complications were classified using the Clavien-Dindo classification system. Univariate and multivariate analyses were performed using IBM SPSS Statistics, version 23.0. RESULTS: Two hundred and fifty-eight patients underwent surgery for UC. 69% were elective, and 31% were urgent/emergent. There were no deaths reported within 30 days of surgery. At 90 days, there were 2 deaths in the elective group and 1 death in the urgent/emergent group. The death in the urgent/emergent group was likely related to the initial surgery, while the elective group death was not directly related to the initial surgery for UC. Complications occurred in 47% of patients. There were no significant differences in rates of complications in either surgical cohort. Majority (62%) of the complications were Clavien-Dindo grade 1 or 2 with no difference in the elective or urgent/emergent group. Unplanned readmissions occurred in 24% of cases. CONCLUSION: Surgery for UC is not associated with any mortality at 30 days and very low mortality at 90 days. However, surgery is associated with an increased rate of minor postoperative complications and readmissions.

Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission: A Prospective Study.

OBJECTIVES: Objective evidence of inflammation has been associated with the risk of relapse in patients with ulcerative colitis (UC) who are in clinical remission. We compared endoscopic and histologic grades for their ability to predict clinical relapse in this patient population. METHODS: Patients with UC in clinical remission were prospectively enrolled into an observational cohort. Baseline endoscopic scores (Mayo) and histological (Geboes) grades and blood markers were collected. All subjects were followed for 12 months and relapse determined using clinical indices. RESULTS: A total of 179 subjects were enrolled into the study and followed for 12 months. Clinical relapse occurred in 23%; 5% were hospitalized, and 2% underwent colectomy. In univariate analysis, the baseline Mayo endoscopy score and the Geboes histology grade were significantly associated with the later development of clinical relapse (P<0.001 for both), but only the histology grade remained significant in a multivariate model (P=0.006). The relative risk of clinical relapse was 3.5 (95% CI 1.9-6.4, P<0.0001) in subjects whose baseline Geboes grade was ≥3.1. The area under the curve was 0.73 for the Geboes histology grade to identify subjects at risk of future clinical relapse. Of the patients in clinical, endoscopic, and histological remission at baseline (n=82), only 7% had a clinical relapse over the subsequent 12 months. CONCLUSIONS: Histology grade has the strongest association with the risk of clinical relapse in patients with UC who are in clinical remission. Consideration should be given to including this end point in evaluating therapy for UC.

An Unexpected Discovery: Postmenopausal Pyloric Endometriosis.

Endometriosis is a benign, estrogen-dependent condition, usually occurring in menstruating and, rarely, in postmenopausal women, in which endometrial glands and stroma grow ectopically outside the uterus. Most often, ectopic endometrial tissue is found within the pelvis and nearby structures. However, endometrial tissue within the upper gastrointestinal tract is very rare and can be a source of bleeding and abdominal pain. Here, we report a case of a 71-year-old postmenopausal woman with hematochezia and diffuse abdominal pain, who was found to have pyloric endometriosis, the pathogenesis of which we will briefly explore.

Histologic markers of inflammation in patients with ulcerative colitis in clinical remission.

BACKGROUND & AIMS: Mucosal healing, based on histologic analysis, is an end point of maintenance therapy for patients with ulcerative colitis (UC). There are few data on how histologic signs of inflammation correlate with endoscopic and peripheral blood measures of inflammation in these patients. We investigated patterns of histologic features of inflammation in patients with UC in clinical remission, and correlated these with endoscopic and biochemical measures of inflammation. METHODS: We performed a prospective observational study of 103 patients with UC in clinical remission undergoing surveillance colonoscopy while receiving maintenance therapy with mesalamine or thiopurines; 2674 biopsy specimens were collected from 708 colonic segments. Each colonic segment was evaluated based on the Mayo endoscopic subscore and the Geboes histology score (range, 0-5.4). Biomarkers were measured in peripheral blood samples. RESULTS: Histologic features of inflammation were found in 54% of patients receiving maintenance therapy; 37% had at least moderate inflammation based on histology scores. Of the 52 patients with endoscopic evidence only of left-sided colitis, 34% had histologic features of inflammation in their proximal colon. Histology scores correlated with endoscopic scores for per-segment inflammation (Spearman ρ = 0.65; P < .001). Patients with histology scores greater than 3.1 had a significantly higher mean level of C-reactive protein than those with scores less than 3.1. There were no differences among treatment groups in percentages of patients with histologic scores greater than 3.1. CONCLUSIONS: Patients in clinical remission from UC still frequently have histologic features of inflammation, which correlate with endoscopic appearance. Patients with at least moderate levels of inflammation, based on histologic grading (score >3.1), have higher serum levels of C-reactive protein, which could be used as a surrogate marker of histologic inflammation.

Complication rates of trainee- versus attending-performed upper gastrointestinal endoscopy.

BACKGROUND: Although esophagogastroduodenoscopy (EGD) is usually the first procedure trainees learn, it is not known whether the involvement of a trainee affects the procedure's complication rate, a key quality and safety indicator. The purpose of this study was to determine whether the complication rate of fellow-performed upper endoscopy differs from that of attending gastroenterologists, and whether that difference varies with the level of training. METHODS: Emergency room visits within 14 days of an outpatient EGD deemed to be probably or definitely related to the EGD were categorized as complications. Complication rates were calculated for attending- and trainee-performed gastrointestinal endoscopies, the latter stratified by level of training. RESULTS: Forty-five attendings and 43 fellows performed 21,899 EGDs during the study period. There were 43 complications (1.96 per 1000 EGDs). Procedures performed by any fellow were more likely to have a complication than those performed by an attending (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.17-4.6). This difference was driven by a higher rate of complications among fellows who had completed general gastroenterology training and were in advanced training (OR 3.8, 95%CI 1.76-8.04); all of these complications involved trainees in interventional endoscopy. Fellows in any year of general gastroenterology training were not more likely to cause complications than attendings. CONCLUSIONS: The rate of complications from EGDs performed by fellows in their general gastroenterology training does not differ from that of attending endoscopists. The complication rate of advanced trainees exceeded that of attendings, but this is likely to be attributable to the higher-risk interventions undertaken by fellows in interventional endoscopy.

Surgery for ulcerative colitis in geriatric patients is safe with similar risk to younger patients.

OBJECTIVE: A prior study indicated that postoperative mortality and complications were higher in geriatrics with inflammatory bowel disease (IBD). We sought to assess the rates of surgical complications and mortality in patients aged ≥65 years after colectomy for ulcerative colitis (UC). METHODS: This is a single center retrospective study at a tertiary care center. We reviewed all hospital discharges with ICD-9 code 556.X between January 2002 and January 2014. Patients were included if they underwent a colectomy for UC. All records were manually reviewed for demographics, complications and mortality within 90 days postoperatively. RESULTS: A total of 259 patients underwent surgery for UC during the study period and 34 patients were ≥65 years old (range 65-82) at the time of their surgery. There was no difference in overall length of stay (10.5 days vs. 9.6 days; P = 0.645) or complication rates (44% vs. 47%; P = 0.854) in the ≥65 cohort compared with the under 65 cohort. Mortality was higher in the geriatric cohort but this included only two deaths within 90 days, one of which was unrelated to the surgery, compared with one death related to surgery within 90 days in the younger cohort. Readmissions occurred in 24% of both cohorts within 90 days. CONCLUSION: Geriatric patients undergoing surgery for UC are not at increased risk of surgery-related morbidity or mortality compared with a younger cohort.

Meta-analysis comparing the efficacy and adverse events of biologics and thiopurines for Crohn's Disease after surgery for ulcerative colitis.

BACKGROUND: Long-term inflammatory complications of IPAA include Crohn's Disease (CD) or "CD-like" (CDL) condition. We performed a meta-analysis to evaluate the efficacy of anti-tumor necrosis factor (anti-TNF) with or without immunomodulator (IM) therapy in this group of patients. METHODS: Literature databases were searched from inception to October 4, 2017. Further searches using references from papers of interest were conducted and, abstracts from major GI conferences were searched. The primary endpoint was: complete clinical response in the two arms. RESULTS: Out of 9 identified studies 4 were included for quantitative analysis. 48% (84/175) were female and mean age was 30.7 years. There was no significant difference in complete clinical response rates, RR 0.58 (95%CI 0.13-2.54, p = 0.5) or partial clinical response rates of RR 0.98 (95%CI 0.52-1.83, p = 0.94). All patients achieved endoscopic and deep remission in the only study reporting these outcomes comparatively in the two arms. There was a trend towards higher risk of major [RR 3.89, (95%C 0.92-16.45 p = 0.09)], and minor adverse events [RR 3.07 (95%CI 0.7-13.52 p = 0.28)] when using anti-TNF therapy compared to anti-TNF with IM. CONCLUSION: We found no difference in outcomes with anti-TNF monotherapy compared to concurrent anti-TNF therapy with IM. Additional studies are needed to define the optimal therapy for CD after IPAA.

Variations in Health Insurance Policies Regarding Biologic Therapy Use in Inflammatory Bowel Disease.

BACKGROUND: The American Gastroenterological Association (AGA) has developed guidelines for the management of ulcerative colitis and Crohn's disease (CD) recommending anti-TNF therapy in moderate-severe disease. However, which drug is used is often dictated by insurance company policies. We sought to determine the insurance policy requirements prior to approval of biologic therapies. METHODS: Using the National Association of Insurance Commissioners report of the top 125 insurance companies by market share in 2014, we reviewed the first 50 that had online policies regarding anti-TNF and vedolizumab available. Policies were reviewed for criteria needed for approval of anti-TNF or vedolizumab therapy, and for compliance with the current AGA clinical pathway recommendations. RESULTS: Ninety-eight percent of policies are inconsistent with the AGA ulcerative colitis pathway and require step-wise drug failure before approval of an anti-TNF. Only 11% of the policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 21% required the failure of two or more anti-TNF agents. Ninety percent of the policies are inconsistent with AGA CD pathway and require step-wise drug failure before approval of an anti-TNF. Seventy-four percent allowed for initiating infliximab specifically for fistulizing CD. Twenty-eight percent required failing of at least two or more drugs before starting anti-TNF. Only 8% policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 28% required the failure of two anti-TNF agents. CONCLUSIONS: The majority of the policies reviewed fail to adhere to the current AGA pathway recommendations for ulcerative colitis and CD. Further interventions are needed to better align policies with optimal evidence-based drug therapy.

Diverticulosis and Diverticulitis.

Diverticular disease is a common condition that is associated with variable presentations. For this review article, we performed a review of articles in PubMed through February 1, 2016, by using the following MeSH terms: colon diverticula, colonic diverticulitis, colonic diverticulosis, colonic diverticulum, colonic diverticula, and diverticula. Diverticula are structural alterations within the colonic wall that classically form "pockets" referred to as diverticula. Diverticula form from herniation of the colonic mucosa and submucosa through defects in the circular muscle layers within the colonic wall. Often this is at the sites of penetrating blood vessels in the colon. Diverticular disease is extremely common, which resulted in 2,682,168 outpatient visits and 283,355 hospitalization discharges for diverticulitis or diverticulosis in 2009. Diverticulosis is one of the most common detected conditions found incidentally on colonoscopy. Risk factors for the development of diverticulitis include obesity, smoking, nonsteroidal anti-inflammatory drugs, corticosteroids, and opiates. In contrast, fiber may be protective, but recent studies have questioned the role of fiber in developing diverticular disease. Most patients with diverticulosis will be asymptomatic, but a subset of patients may develop nonspecific abdominal pain (isolated or recurrent), diverticulitis, or segmental colitis associated with diverticulosis. Classically, the treatment of diverticulitis has included antibiotics for all patients. More recent evidence indicates that in mild to even moderate uncomplicated diverticulitis, antibiotics may not be as necessary as initially believed. In more complicated diverticulitis, intravenous antibiotics and surgery may be necessary. Once a patient has had an attack of diverticulitis, increasing fiber may help prevent future attacks. Other modalities such as 5-aminosalicylate products, antibiotics, and probiotics are still of unclear benefit in preventing future episodes of diverticulitis. Similarly, even when patients develop recurrent episodes of diverticulitis, surgery may not be necessary as a prophylactic treatment.

Smoking and immunomodulators do not influence the response or duration of response to infliximab in Crohn's disease.

OBJECTIVE: Clinical predictors for infliximab response are still unknown. Identifying predictors of response to infliximab in Crohn's disease may improve our selection of patients. METHODS: Two hundred patients with luminal (61%) or fistulous (39%) Crohn's disease and at least 6 months of follow-up following a total of 416 infliximab infusions were evaluated. Clinical response and duration of response were the primary endpoints. RESULTS: Patients with fistulous disease had a higher response rate (83% versus 70%, P = 0.044) and a significantly longer duration of response compared with patients with luminal disease (17.4 versus 10.1 wks, P = 0.017). For luminal disease, nonsmokers and smokers had similar response rates (74% versus 64%, P = 0.5) and similar durations of response (9.4 wks versus 8.4 wks P = 0.6) while patients taking concurrent immunomodulators had similar response rates compared with those not taking immunomodulators (74% versus 71%, P = 0.9) and similar durations of response (10.4 wks versus 10.6 wks, P = 0.9). For fistulous disease, response rates (89% versus 83% P = 0.9) and duration of response (16.9 wks versus 10.1 wks, P = 0.10) were similar between nonsmokers and smokers and concurrent immunomodulators had no effect on response (89% versus 86%, P = 0.9) or duration of response (19.8 wks versus 15.4 wks, P = 0.46). Multivariable analysis confirmed that neither smoking, corticosteroids, immunomodulator therapy, gender, age, age of disease onset, disease duration, nor luminal disease location significantly influenced response or duration of response. CONCLUSIONS: Patients with fistulous disease had a higher response rate and a significantly longer duration of response compared with patients with luminal disease. However, among patients with luminal or fistulous disease, neither smoking nor immunomodulators had any effect on response or duration of response.

Aggressive cutaneous T-cell lymphomas after TNFalpha blockade.

Pharmacologic blockade of TNFalpha has been a highly effective approach to treating several immunologically mediated diseases, including rheumatoid arthritis, Crohn's disease, and psoriatic arthritis. 1,2,3 Both etanercept, the recombinant extracellular domain of the tumor necrosis factor receptor 2 (TNFR2), and infliximab, a humanized murine antibody, bind TNFalpha and block its interaction with cell surface receptors. Recently, it has become clear that blockade of TNFalpha action is profoundly immunosuppressive, and may result in reactivation of tuberculosis and histoplasmosis, as well as the emergence of B-cell lymphomas. 4,5,6 In this report, we describe two cases of cutaneous and systemic T-cell lymphoma that progressed rapidly in the setting of TNFalpha blockade. Both cases were characterized by rapid onset, a fulminant clinical course with extensive cutaneous and systemic involvement, and death within months of diagnosis.

Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission.

BACKGROUND: Patients with ulcerative colitis (UC) who are in clinical remission may still have underlying endoscopic inflammation, which is associated with inferior clinical outcomes. The goal of this study was to determine the prevalence of active endoscopic disease, and factors associated with it, in patients with UC who are in clinical remission. METHODS: Prospective observational study in a single center. Patients with UC in clinical remission (by Simple Clinical Colitis Activity Index) were enrolled prospectively at the time of surveillance colonoscopy. Disease phenotype, endoscopic activity (Mayo subscore), and histologic score (Geboes) were recorded, and blood was drawn for peripheral blood biomarkers. RESULTS: Overall, 149 patients in clinical remission were prospectively enrolled in this cohort; 81% had been in clinical remission for >6 months, and 86% were currently prescribed maintenance medications. At endoscopy, 45% of patients in clinical remission had any endoscopic inflammation (Mayo endoscopy subscore >0), and 13% had scores >1. In a multivariate model, variables independently associated with a Mayo endoscopic score >1 were remission for <6 months (P = 0.001), white blood count (P = 0.01), and C-reactive protein level (P = 0.009). A model combining these 3 variables had a sensitivity of 94% and a specificity of 73% for predicting moderate-to-severe endoscopic activity in patients in clinical remission (area under the curve, 0.86). In an unselected subgroup of patients who had peripheral blood mononuclear cell messenger RNA profiling, GATA3 messenger RNA levels were significantly higher in patients with endoscopic activity. CONCLUSIONS: Duration of clinical remission, white blood count, and C-reactive protein level can predict the probability of ongoing endoscopic activity, despite clinical remission in patients with UC. These parameters could be used to identify patients who require intensification of treatment to achieve mucosal healing.

Impact of a patient-support program on mesalamine adherence in patients with ulcerative colitis--a prospective study.

BACKGROUND: Patient adherence to medications, particularly mesalamine, is reported to be low in patients with ulcerative colitis. We sought to determine whether a nurse-delivered patient-support program could improve medication adherence in these patients. METHODS: Patients prescribed mesalamine for ulcerative colitis prospectively received either a 23 week, nurse-delivered, patient support program (PSP) by phone, or standard care (SC). Medication adherence and quality of life were measured before and at 3 and 6 months after the program started. RESULTS: Eighty-one patients completed the study; 60 who received standard care, and 21 who received the PSP. Patients were in remission (mean SCAI score 3) at enrollment. Mean % of prescribed mesalamine refilled was 71% and 74% in the SC and PSP groups at 3 months (p=0.7), and 73% and 84% at 6 months (p=0.4). The proportion of adherent patients at 3 months (39% vs 44%, p=0.7) and 6 months (50% vs 67%, p=0.3) were similar between the SC and PSP groups. There was no association between use of the PSP and adherence at 3 (OR 1.2, 95% CI 0.4 to 3.8) or 6 months (OR 2, 95% CI 0.6 to 7). The change from baseline in SIBDQ scores were similar between SC and PSP groups at 3 months (+0.3 vs +0.2, p=0.8), and 6 months (+0.6 vs +0.2, p=0.2). CONCLUSIONS: This nurse-delivered patient-support program did not significantly improve medication adherence or quality-of-life beyond standard care at short and medium-term time-points. Simply discussing and measuring adherence improved mesalamine adherence in both groups in this study.

Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.

BACKGROUND & AIMS: We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI. METHODS: Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat. RESULTS: Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06. CONCLUSIONS: Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions.