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Marla C Dubinsky

Publications and source records attributed to Marla C Dubinsky.

18 recordsLinked to original sources

Case report: evidence for transplacental transfer of maternally administered infliximab to the newborn.

BACKGROUND & AIMS: Control of Crohn's disease (CD) is important for conception and sustaining a pregnancy to term. Small series of infliximab use during pregnancy have reported favorable fetal and maternal outcomes. As a result of heightened maternal concern triggered by recent labeling changes, infliximab levels were measured in the newborn of a mother treated with infliximab. METHODS: Serum and breast milk infliximab levels were measured by enzyme-linked immunosorbent assay. RESULTS: A 32-year-old woman with treatment-refractory CD continued infliximab therapy throughout pregnancy. Five infusions of infliximab, 10 mg/kg, the last one 2 weeks before delivery, successfully controlled her symptoms. Six weeks after delivery, the breast-fed infant's serum infliximab level was 39.5 microg/mL. Infliximab was not detected in the breast milk. Serial measurements revealed a continued slow decline of the infant's infliximab levels during the following 6 months, despite resumption of breast-feeding and subsequent retreatments of the mother with infliximab. CONCLUSIONS: Clinically significant infliximab levels were detected in the offspring. High infliximab levels in the serum of this infant are likely due to placental transfer, not breast-feeding. Similar to other maternally acquired antibodies, the half-life of infliximab appears prolonged in newborns. The true short-term and long-term implications of exposure to infliximab during the newborn period are unknown. Patients and physicians must be informed about in utero exposure to infliximab and potentially other therapeutic antibodies. The timing of infusions to minimize antibody transfer to the fetus might be an important strategic consideration when therapeutic antibodies are used in pregnancy.

Adult↗

Challenges in pediatric inflammatory bowel disease.

It is estimated that of the >1 million individuals in the United States with inflammatory bowel disease (IBD), approximately 100,000 are children. IBD that begins in childhood affects the individual at a critical period of growth and development. Children with Crohn's disease and ulcerative colitis may experience complications such as growth failure, school absence, and depression. In addition, because children with IBD have fewer environmental confounders such as smoking, children may be an excellent population to study microbial and immune interactions. Despite these opportunities, the discipline of pediatric IBD investigation is still in its infancy. In September of 2005, a group of investigators with expertise in pediatric IBD met in Boston (Massachusetts) to review the current status of childhood IBD research and to develop research priorities that warranted funding from the Crohn's and Colitis Foundation of America. The group included pediatricians, internists, basic scientists, clinical investigators, and members of the administrative staff and board of the Crohn's and Colitis Foundation of America. The research needs in respective areas were outlined by the heads of 10 focus groups, each with expertise in their respective fields (genetics, psychosocial issues, epidemiology, microbiology, immunology, quality improvement, pharmacogenomics, nutrition, growth and skeletal health, and clinical trials). Before the conference, heads of the research focus groups developed their proposals with experts in the field. At the end of the conference, members of the focus groups and members of the steering committee rated the proposed areas of study in terms of feasibility and importance. It was recommended that the Crohn's and Colitis Foundation of America focus its initial efforts in pediatric IBD in 5 areas: the effects of inflammation on growth and skeletal development, the genetics of early-onset IBD, the development of quality improvement interventions to standardize and improve clinical care of children with IBD, the immunology of childhood IBD, and the diagnosis and treatment of psychosocial sequelae of childhood IBD. At the conclusion of the meeting, investigators discussed the formation of a multicenter collaborative network to advance clinical and basic research in the field.

Child↗

Antibodies to I2 predict clinical response to fecal diversion in Crohn's disease.

OBJECTIVES: Fecal diversion is occasionally indicated in patients with advanced perianal or colorectal Crohn's disease (CD). Because CD may result from an aberrant immunologic response to bacteria within the gut lumen, fecal diversion should be effective in managing these complications. However, not all patients achieve a clinical response after fecal diversion. CD patients can be characterized by their antibody responses against Pseudomonas fluorescens (I2), E.coli outer membrane porin C (OmpC), oligomannan (anti-Saccharomyces cerevisiae antibodies [ASCA]), and antinuclear antigens (perinuclear antineutrophil cytoplasmic antibodies [pANCA]). This study examines the association between clinical features and seroreactivity to these microbial and auto-antigens in predicting a clinical response to fecal diversion. METHODS: Twenty-seven consecutive CD patients undergoing fecal diversion were included. Sera were drawn and tested for anti-I2, anti-OmpC, ASCA, and pANCA in a blinded fashion. Response was assessed using clinical parameters. RESULTS: Seventeen (63%) patients underwent fecal diversion for medically resistant proctocolitis and 10 (37%) for severe perianal disease. Median follow-up was 41 months. Seventeen (63%) patients achieved a clinical response. No preoperative clinical or surgical factor predicted response to diversion. Clinical response after fecal diversion was seen in 15 of 16 (94%) patients who were I2 positive compared with only 2 of 11 (18%) patients who were I2 negative (P = 0.0001). Seroreactivity to OmpC, ASCA, or pANCA was not associated with a clinical response to diversion. CONCLUSION: Expression of I2 antibodies against a bacterial antigen of Pseudomonas fluorescens was highly associated with clinical response to fecal diversion in CD patients.

Adult↗

Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression.

BACKGROUND AND AIM: Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. METHODS: Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. RESULTS: Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p = 0.03). Pediatric CD patients positive for > or =1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). CONCLUSIONS: The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.

Adolescent↗

Safety and efficacy of adalimumab (D2E7) in Crohn's disease patients with an attenuated response to infliximab.

OBJECTIVES: Although infliximab is highly effective in the treatment of Crohn's disease (CD), attenuated response to infliximab may develop over time in a subgroup of patients. The aim of our study was to examine the safety and efficacy of adalimumab (D2E7), a fully humanized anti-TNF-alpha Ab, in CD patients who had experienced an attenuated response to infliximab. METHODS: Fifteen patients with active CD who experienced an attenuated response to infliximab were treated with adalimumab over a 6-month period. Patients, received a loading dose of 80 mg subcutaneously followed by 40 mg every 2 wk. The clinical response to adalimumab was classified as complete response, partial response, or nonresponse. RESULTS: Two patients received the loading dose of adalimumab but did not have adequate follow-up evaluations. Of the remaining 13 patients, 7 (54%) had a complete response, 4 (31%) had a partial response, and 2 (15%) were nonresponders. In six patients, the maintenance dose was increased in order to maintain clinical response. Eight of 11 (73%) patients on concurrent corticosteroids were able to discontinue or significantly decrease the dose of the steroids. Adalimumab was well tolerated without signs or symptoms of allergic reaction except in two patients who developed an injection site reaction. CONCLUSIONS: Our preliminary data suggest that adalimumab may be a safe and effective therapy for patients with CD who have experienced an attenuated response to infliximab.

Adalimumab↗

A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine.

BACKGROUND: Azathioprine (AZA) is effective for the maintenance of a steroid free remission in Crohn's disease (CD). Thiopurine methyltransferase (TPMT) is important for the metabolism of AZA and influences the production of active AZA metabolites. AZA dose selection based on pharmacogenetic testing of TPMT and metabolite monitoring (MM) may offer a safety and efficacy advantage over traditional dosing strategies. We performed a decision analysis to estimate the potential costs and effectiveness of TPMT screening and MM as disease management strategies for CD. METHODS: Strategies applying TPMT and/or MM to influence treatment decisions were compared to community care (CC). The impact on toxicity minimization and improved time to initial and sustained response was evaluated. A 1-yr model was developed from the third-party payer perspective for mild to moderately chronically active, steroid-treated CD patients. Effectiveness and toxicity defined by time to response CD activity index (CDAI <150, +/- steroids) or time to sustained response (CDAI <150, off steroids x 8 wk) and reduction in leukopenic events, respectively. One- and two-way sensitivity analyses were conducted to determine the effect of varying individual estimates from those used in the base-case analysis. RESULTS: MM, TPMT, and TPMT + MM strategies as compared to CC achieved an earlier time to initial response (18.66, 18.96, and 19.10 vs. 22.41 wk, respectively) and sustained response (39.83, 42.91, and 39.8 vs. 45.36 wk, respectively). The least costly strategy at 1 yr was TPMT ($3,861) and the most costly strategy was CC ($7,142). Each alternative strategy was shown to dominate CC (i.e., less costs and faster time to response or sustained response). The cost-effectiveness rankings were robust to sensitivity analyses on key variables. CONCLUSION: The addition of alternative strategies to CC may improve AZA outcomes and reduce the total cost of care for steroid treated chronically active CD patients, with TPMT being more beneficial for initial response to treatment and MM being more beneficial for sustained response to treatment.

Azathioprine↗

Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease.

BACKGROUND AND AIMS: Wireless capsule enteroscopy (WCE) offers the potential to directly visualize the entire small bowel and identify superficial lesions not detected by traditional endoscopy and radiography. The aim of this study is to assess the clinical utility of WCE in the evaluation of patients with known or suspected inflammatory bowel disease (IBD). METHODS: Fifty patients with ongoing symptoms underwent Given M2A endoscopic capsule examinations. Indications included: (1) evaluation for small-bowel involvement in patients with IBD with isolated colitis (n = 22), (2) determination of the extent of small-bowel disease in patients with Crohn's disease (CD; n = 20), and (3) workup of suspected IBD (n = 8). Outcome measures were classified as diagnostic when multiple ulcerations were present, suspicious when </=3 ulcerations were seen, and nonspecific or normal. RESULTS: WCE findings were diagnostic for CD in 20 patients and suspicious for small-bowel CD in 10 patients. Seventeen of 20 patients with diagnostic WCE findings improved with increased IBD-directed medical therapy, as did 7 of 10 patients with suspicious study results. WCE was normal or showed nonspecific findings in the remaining 20 patients. Notably, identification of small-bowel lesions in 5 patients with a previous history of isolated colitis resulted in a change in diagnosis to CD after confirmatory ileoscopy with biopsy. CONCLUSIONS: Results of this preliminary study suggest that WCE is a novel and potentially clinically useful method of directly visualizing and diagnosing small-bowel lesions in patients with IBD that can be missed by traditional endoscopic and radiological procedures.

Adolescent↗

Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety.

6-Mercaptopurine and its prodrug azathioprine remain the mainstay of immunomodulator therapy for the maintenance of a steroid-free remission in patients with IBD. Recent evidence suggests that the cytotoxic and immunosuppressive effects of azathioprine might be mediated via the induction of lymphocyte apoptosis by its active metabolites, 6-thioguanine nucleotides. The therapeutic benefits of thiopurines have been shown to correlate with the concentration of 6-thioguanine nucleotides. Inherited differences in drug metabolism and disposition can significantly impact the safety and efficacy of these drugs. The thiopurine methyltransferase enzyme plays an important role in the metabolism of 6-mercaptopurine and azathioprine and in the determination of thiopurine cytotoxicity. By gaining an understanding of the pharmacology and metabolism of thiopurine therapy and putting it into the clinical context, clinicians will be able to optimize thiopurine therapy in IBD.

Azathioprine↗

A pilot study of adalimumab in infliximab-allergic patients.

The anti-TNF-alpha antibody infliximab (Remicade) is highly effective in the treatment of Crohn's disease. A subset of patients experience allergic reactions as a result of antibodies to infliximab (ATIs). The purpose of the current study is to describe the safety and efficacy of adalimumab (Humira) in patients previously allergic or intolerant to infliximab. Adalimumab is an anti-TNF-alpha agent containing only human peptide sequences. Seven patients have been treated with adalimumab who had experienced immediate- or delayed-hypersensitivity reactions to infliximab and one with infliximab-induced lupus. Except for injection site discomfort, adalimumab was well tolerated without signs or symptoms of allergic reactions. One patient who had previously received pooled human immunoglobulin developed a pruritic rash after each dose of adalimumab. Patients with active disease who had previously experienced a robust response to infliximab responded to adalimumab as reflected by an improvement in Harvey-Bradshaw index and inflammatory markers. Based on these preliminary data, adalimumab may be a safe and effective substitute for infliximab-allergic patients. Individuals who have been exposed to human antibodies may be sensitized to other human antibodies such as adalimumab.

Adalimumab↗

Early hepatic nodular hyperplasia and submicroscopic fibrosis associated with 6-thioguanine therapy in inflammatory bowel disease.

BACKGROUND: 6-Thioguanine (6-TG) has been used as an alternative thiopurine for inflammatory bowel disease (IBD) patients not responsive to or intolerant of azathioprine (AZA) and 6-mercaptopurine (6-MP). 6-TG-related hepatotoxicity, including liver biochemistry value elevations, sinusoidal collagen deposition on electron microscopy, and veno-occlusive disease, have been described related to its use as therapy for neoplastic disease. METHODS: We studied 38 liver biopsies from patients treated with 6-TG, almost all of whom (n = 125) received 6-TG for 1 to 3 years at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center. All biopsies were fixed in 4% buffered formalin and prepared in the usual manner. Hematoxylin and eosin, Masson's trichrome (trichrome), and reticulin silver impregnation (reticulin) stained slides were studied. In 23 cases, tissue was also prospectively fixed in glutaraldehyde and processed for electron microscopy. RESULTS: In 20 of the 37 patients studied (53%), nodular regeneration of varying degree was seen with reticulin. In only 4 of these 20 instances (11% of the total) were the changes seen with hematoxylin and eosin and in 3 of the 4, only in retrospect after studying the reticulin preparation. Minimal fibrosis was seen with trichrome in only 13 biopsies (34%), but sinusoidal collagen deposition was observed in 14 of the 23 cases studied with electron microscopy (60%). The biopsy from the 1 patient with nodular hyperplasia obvious with hematoxylin and eosin also demonstrated changes of venous outflow obstruction. CONCLUSIONS: 6-TG-treated IBD patients are at significant risk for nodular hyperplasia, early fibrosis and, less often, venous outflow disease (Budd-Chiari). The natural history of these changes is unknown and follow-up biopsies are needed to determine histologic and clinical sequela. Patients not demonstrating nodular hyperplasia or fibrosis who continue with 6-TG because there are no better therapeutic choices should be periodically rebiopsied.

Adolescent↗

Early nodular hyperplasia of the liver occurring with inflammatory bowel diseases in association with thioguanine therapy.

CONTEXT: Nodular hyperplasia (also referred to as nodular regenerative hyperplasia and nodular regenerative hyperplasia of the liver) is a sequel to therapy with thioguanine in patients with hematologic malignancies. Recently, 6-thioguanine has been used to treat patients with inflammatory bowel disease who have been resistant to other forms of therapy. OBJECTIVE: To study liver biopsies from 3 patients with inflammatory bowel disease who had received thioguanine for more than a year, and who had elevated serum liver enzyme values and underwent percutaneous liver biopsy. DESIGN: Percutaneous liver biopsies and histologic examinations were performed, including staining with the reticulin silver impregnation method. RESULTS: All 3 patients had foci of nodular regenerative hyperplasia, which was best seen with the reticulin silver impregnation method. CONCLUSIONS: Thioguanine-treated inflammatory bowel disease patients are at risk for the development of nodular hyperplasia. Reticulin-stained histologic sections are necessary to recognize this change. Further studies are needed to determine the frequency and significance of this change.

Adult↗

Optimizing immunomodulator therapy for inflammatory bowel disease.

6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) remain the mainstay of immunomodulator therapy for the maintenance of steroid-free remission in patients with inflammatory bowel disease (IBD). Traditional dosing strategies for initiation of thiopurines are often based on weight or empirically chosen. Dosing based on an understanding of an inherited difference in drug disposition and metabolism may provide a safer alternative. The thiopurine methyltransferase (TPMT) enzyme plays a pivotal role in the metabolism of 6-MP and AZA and is critical to the determination of thiopurine toxicity. The therapeutic benefits of thiopurines correlate best with concentration of the active 6-thioguanine (6-TGN) metabolites. Reports suggest that therapeutic response can be maximized when patients achieve therapeutic 6-TGN levels. Pharmacogenetic dosing based on TPMT and pharmacokinetic dosing based on 6-TGN levels may offer a safety and efficacy advantage over traditional dosing strategies and provide a novel mechanism for optimizing immunomodulator therapy in IBD.

Adjuvants, Immunologic↗

6-thioguanine can cause serious liver injury in inflammatory bowel disease patients.

BACKGROUND & AIMS: Thioguanine (6-TG) has been studied as an alternative thiopurine in inflammatory bowel disease (IBD). Short-term safety and efficacy data were favorable. Experience with 6-TG in patients with acute lymphoblastic leukemia raised long-term safety concerns when implicated in nodular regenerative hyperplasia (NRH) of the liver and portal hypertension. The aim of this study was to describe the association between 6-TG and NRH in IBD. METHODS: Liver chemistries and complete blood counts were monitored, and patients were encouraged to undergo liver biopsy. Clinical data were collected by chart review, and associations were tested by univariate and multivariable analyses. Patients were classified based on the presence (group 1) or absence (group 2) of laboratory abnormalities. RESULTS: Laboratory abnormalities occurred in 29 of 111 patients (26%). Elevations of liver enzymes and a decrease in platelet counts (<200,000) were most commonly observed. Male gender (odds ratio, 2.9; 95% CI, 1.1-7.3; P < 0.03) and preferential 6-methylmercaptopurine production on 6-mercaptopurine/azathioprine (odds ratio, 3.0; 95% CI, 1.2-7.4; P < 0.04) were independently associated with laboratory abnormalities. No association was seen with duration of 6-TG treatment, cumulative dose, or 6-TG nucleotide levels. The median increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels was 39, 30, and 75 U/L, respectively, in group 1, and the median decrease in platelet count was 115,000 in group 1 versus 7000 in group 2 (P < 0.001). NRH occurred in 76% of patients undergoing biopsy in group 1 and 33% in group 2. CONCLUSIONS: NRH is a common finding in 6-TG-treated patients with IBD. The progression or reversibility of NRH remains unknown. Our findings suggest that 6-TG should not be considered as therapy for patients with IBD.

Adolescent↗

Thioguanine: a potential alternate thiopurine for IBD patients allergic to 6-mercaptopurine or azathioprine.

OBJECTIVE: Approximately 10% of inflammatory bowel disease (IBD) patients receiving 6-mercaptopurine (6-MP) or azathioprine (AZA) develop drug hypersensitivity reactions necessitating early discontinuation of these traditional thiopurines. These allergic reactions typically reoccur upon rechallenge. Our recently published pilot study suggested that thioguanine (6-TG), a closely related thiopurine, was efficacious and well tolerated in IBD patients resistant to 6-MP/AZA. The aim of this study was to determine if hypersensitivity reactions to 6-MP/AZA reoccur with 6-TG therapy. METHODS: IBD patients allergic to 6-MP and/or AZA were treated with 6-TG as an alternate thiopurine. Hypersensitivity reactions to 6-MP/AZA must have been documented within 6 wk of 6-MP/AZA initiation. RESULTS: 6-TG was initiated in 21 IBD patients at a median (range) dose of 20 (10-40) mg/day. 6-TG hypersensitivity reaction occurred in only four of 21 (19%) patients after a median time interval of 9 days. Pancreatitis did not reoccur with 6-TG. Eighty-two percent of 6-TG tolerant patients were assessed as improved at last follow-up. CONCLUSIONS: These results suggest that 6-TG may be considered as a possible alternate thiopurine in patients allergic to traditional 6-MP/AZA. Despite these favorable results, candidates for 6-TG should be selected with caution, and its use should be reserved for IBD patients well informed about potential toxicities.

Adult↗

6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Approximately 40% of inflammatory bowel disease (IBD) patients fail to benefit from 6-mercaptopurine (6-MP)/azathioprine (AZA). Recent reports suggest 6-thioguanine nucleotide (6-TGN) levels (>235) independently correlate with remission. An inverse correlation between 6-TGN and thiopurine methyltransferase (TPMT) has been described. The objectives of this study were to determine whether dose escalation optimizes both 6-TGN levels and efficacy in patients failing therapy because of subtherapeutic 6-TGN levels and its effect on TPMT. METHODS: Therapeutic efficacy and adverse events were recorded at baseline and upon reevaluation after dose escalation in 51 IBD patients. 6-MP metabolite levels and TPMT activity were recorded blinded to clinical information. RESULTS: Fourteen of 51 failing 6-MP/AZA at baseline achieved remission upon dose escalation, which coincided with significant rises in 6-TGN levels. Despite increased 6-MP/AZA doses, 37 continued to fail therapy at follow-up. Dose escalation resulted in minor changes in 6-TGN, yet a significant increase in 6-methylmercaptopurine ribonucleotides (6-MMPR) (P < or = 0.01) and 6-MMPR:6-TGN ratio (P < 0.001). 6-MMPR rises were associated with dose-dependent hepatotoxicity in 12 patients (24%). TPMT was not influenced by dose escalation. CONCLUSIONS: Serial metabolite monitoring identifies a novel phenotype of IBD patients resistant to 6-MP/AZA therapy biochemically characterized by suboptimal 6-TGN and preferential 6-MMPR production upon dose escalation.

Adolescent↗

Suspected inflammatory bowel disease--the clinical and economic impact of competing diagnostic strategies.

OBJECTIVES: The suspicion of IBD in patients presenting with nonspecific abdominal pain and diarrhea results in the extensive use of invasive diagnostic testing in patients likely to have a functional GI disorder. Noninvasive serodiagnostic tests, however, accurately identify IBD and may serve as effective screening tools. The objective of this study was to examine the cost-effectiveness of initial serodiagnostic screening followed by standard invasive testing, compared to standard invasive testing alone, in patients presenting with uninvestigated symptoms suggestive of IBD. METHODS: Decision analysis was performed to compare the costs and outcomes of competing diagnostic strategies. Probability estimates were derived from the medical literature and expert opinion. Costs estimates were obtained from the Medicare Fee schedule and the cost-analysis was done from a third party payer perspective. The target population was patients with uninvestigated symptoms suggestive of IBD. The outcome measure was cost per correct diagnosis in competing strategies and was assessed at 1 yr. RESULTS: In the base case analysis, the serodiagnostic strategies were dominant; they were less costly and more accurate than the standard invasive strategies. Sequential serodiagnostic strategies resulted in the largest cost savings ($550 per average patient) with an average cost per correct diagnosis of $1640 compared to $2188 for standard invasive testing. Cost savings were attributable to a 39% reduction in the use of invasive tests. The results were robust to varying model estimates over prespecified ranges in the sensitivity analyses. When costs of invasive testing are reduced by 80% or the prevalence of IBD is at least 83%, serodiagnostic strategies are no longer the most cost-effective. CONCLUSIONS: Initial serodiagnostic screening strategies may represent a cost-effective alternative to standard invasive diagnostic strategies. The economic benefits seem to be achieved by avoiding invasive evaluations in patients without IBD. Confirmation of these findings in a prospective comparative trial seems to be warranted.

Cost-Benefit Analysis↗