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1.  Infliximab therapy for Crohn’s-like disease in common variable immunodeficiency complicated by massive intestinal hemorrhage: a case report 
BMC Research Notes  2014;7:382.
Background
Common variable immune deficiency is the most frequently encountered immunodeficiency in adults, which is characterized by low levels of serum immunoglobulins. Common variable immune deficiency can present with inflammatory bowel disease-like colitis because of the dysregulated immune system; paradoxically activated T cell receptor pathways are thought to be pivotal in pathogenesis of common variable immune deficiency-related colitis. Treatment for severe complications, such as gastrointestinal bleeding, is not established. We report a case of common variable immune deficiency-related Crohn’s-like disease presenting massive melena, which was successfully treated by short course infliximab therapy.
Case presentation
A 26-year-old Japanese man with history of common variable immune deficiency presented with diarrhea, abdominal pain, and fever. Venous administration of antibiotics did not improve his symptoms. Colonoscopy revealed multiple longitudinal ulcers as well as cobblestone-like change in the ileum end and the ascending colon. Histopathological examination of biopsy specimen showed erosion and infiltration of T lymphocytes with lack of B cells. Intravenous hyperalimentation, mesalazine, and steroid did not improve the symptoms and the patient subsequently presented with massive melena. Colonoscopy revealed a protuberant vessel on one of the ulcers in the ascending colon. Endoscopic clipping was repeatedly performed for hemostasis, which was only temporarily successful. In an attempt to manage the bleeding and colitis, a trial of infliximab was given on week 0, week 2 and week 6. Gastrointestinal hemorrhage from the ulcer halted immediately after the first infliximab injection. Colonoscopy performed after the third infliximab showed remarkable improvement in the ileocolitis. No evidence of increased susceptibility to infections was observed and the patient has been in clinical remission for 3 years.
Conclusions
We present this case together with review of literature to share our experience of encountering common variable immune deficiency complicating severe Crohn’s-like disease and to support that infliximab is a safe and effective treatment that can promptly manage life-threatening intestinal hemorrhage in common variable immune deficiency-related colitis.
doi:10.1186/1756-0500-7-382
PMCID: PMC4229744  PMID: 24952714
Common variable immunodeficiency; Inflammatory bowel disease; T lymphocyte; Colitis
2.  Long-Term Surgical Recurrence, Morbidity, Quality of Life, and Body Image of Laparoscopic-Assisted vs. Open Ileocolic Resection for Crohn’s Disease: A Comparative Study 
Diseases of the Colon and Rectum  2008;51(6):858-867.
Purpose
Several studies have compared conventional open ileocolic resection with a laparoscopic-assisted approach. However, long-term outcome after laparoscopic-assisted ileocolic resection remains to be determined. This study was designed to compare long-term results of surgical recurrence, quality of life, body image, and cosmesis in patients who underwent laparoscopic-assisted or open ileocolic resection for Crohn’s disease.
Methods
Seventy-eight consecutive patients who underwent ileocolic resection during the period 1995 to 1998 were analyzed; 48 underwent a conventional open approach in the Academic Medical Centre (Amsterdam, The Netherlands) and 30 underwent a laparoscopic-assisted approach in the Leiden University Medical Centre (Leiden, The Netherlands). Primary outcome parameters were reoperation and readmission rate. Secondary outcome parameters were quality of life, body image, and cosmesis.
Results
The two groups were comparable for characteristics of sex, age, and immunosuppressive therapy. Seventy-one patients had a complete follow-up of median 8.5 years. Resection for recurrent Crohn’s disease was performed in 6 of 27 (22 percent) and 10 of 44 (23 percent) patients in the laparoscopic and open groups, respectively. Reoperations for incisional hernia were only performed after conventional open ileocolic resection (3/44 = 6.8 percent). Quality of life and body image were comparable, but cosmesis scores were significantly higher in the laparoscopic group.
Conclusions
Despite small numbers, we found that surgical recurrence and quality of life after laparoscopic-assisted and open ileocolic resection were comparable. Incisional hernias occurred only after open ileocolic resection, and laparoscopic-assisted ileocolic resection resulted in a significantly better cosmesis.
doi:10.1007/s10350-008-9195-6
PMCID: PMC2440934  PMID: 18266036
Crohn’s disease; Laparoscopy; Ileocolic resection; Laparoscopic; CD; Long-term morbidity; Body image; Quality of life
3.  Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT) 
BMJ Open  2014;4(4):e005091.
Introduction
Many patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC.
Methods and analysis
Between May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants’ scores, analysed by Cox regression. Secondary outcome measures include: the CCQ—an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures—EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants’ views on therapies for acute severe UC and healthcare professionals’ views on the two drugs and their administration.
Ethics and dissemination
The Research Ethics Committee for Wales has given ethical approval (Ref. 08/MRE09/42); each participating Trust or Health Board has given NHS Reseach & Development approval. We plan to present trial findings at international and national conferences and publish in high-impact peer-reviewed journals.
Trial registration number
ISRCTN: 22663589; EudraCT number: 2008-001968-36
doi:10.1136/bmjopen-2014-005091
PMCID: PMC4010821  PMID: 24785401
Ulcerative colitis; Acute severe; Steroid refractory; Ciclosporin; Infliximab; Randomised controlled trial
4.  Cost-Effectiveness of Infliximab for the Treatment of Acute Exacerbations of Ulcerative Colitis in the Netherlands 
Biologics in Therapy  2012;3(1):45-60.
Introduction
Infliximab is registered for the treatment of moderate-to-severe active ulcerative colitis (UC) adult patients who have had an inadequate response, or are intolerant, or have medical contraindications to therapy including corticosteroids and 5-aminosalicylates or thiopurines (6-mercaptopurine [6-MP] or azathioprine [AZA]). The authors estimate the costs and effects and evaluate the cost-effectiveness of infliximab at the licensed dose of 5 mg/kg versus cyclosporine or surgery for the treatment of adult Dutch patients hospitalized with acute exacerbations of UC, refractory to intravenous steroids.
Method
An existing decision analytical model was updated to simulate disease progression of hospitalized UC patients in the Netherlands, refractory to intravenous corticosteroids, and to estimate the costs and benefits associated with infliximab compared to cyclosporine and surgery over a 1-year time horizon. Colectomy rates were derived from infliximab and cyclosporine randomized trials and synthesized using multiple treatment comparison methods. The utility estimates associated with health states of ulcerative colitis patients were obtained from the literature. Resource use and drug use frequencies as well as unit costs were obtained from Dutch sources. The primary effectiveness measure used in the analysis was quality-adjusted life years (QALYs).
Results
For a typical UC patient with body weight of 70 kg, the costs of treatment with infliximab, cyclosporine, and surgery over a 1-year treatment period were €17,062, €14,784, €13,979, respectively. The associated numbers of QALYs were 0.80, 0.70, and 0.58 for infliximab, cyclosporine, and surgery respectively. The incremental cost-effectiveness ratio for infliximab was €24,277 per QALY gained compared to cyclosporine, and €14,639 per QALY gained compared to surgery.
Conclusions
Infliximab induction regimen appears to be a cost-effective treatment option in comparison to cyclosporine and surgery for hospitalized patients with acute exacerbations of UC, refractory to intravenous corticosteroids in the Netherlands.
doi:10.1007/s13554-012-0007-0
PMCID: PMC3873082  PMID: 24392304
Colectomy; Cost-effectiveness; Cyclosporine; Gastroenterology; Infliximab; The Netherlands; Ulcerative colitis
5.  Cost-Effectiveness of Infliximab for the Treatment of Acute Exacerbations of Ulcerative Colitis in the Netherlands 
Biologics in Therapy  2012;3(1):45-60.
Introduction
Infliximab is registered for the treatment of moderate-to-severe active ulcerative colitis (UC) adult patients who have had an inadequate response, or are intolerant, or have medical contraindications to therapy including corticosteroids and 5-aminosalicylates or thiopurines (6-mercaptopurine [6-MP] or azathioprine [AZA]). The authors estimate the costs and effects and evaluate the cost-effectiveness of infliximab at the licensed dose of 5 mg/kg versus cyclosporine or surgery for the treatment of adult Dutch patients hospitalized with acute exacerbations of UC, refractory to intravenous steroids.
Method
An existing decision analytical model was updated to simulate disease progression of hospitalized UC patients in the Netherlands, refractory to intravenous corticosteroids, and to estimate the costs and benefits associated with infliximab compared to cyclosporine and surgery over a 1-year time horizon. Colectomy rates were derived from infliximab and cyclosporine randomized trials and synthesized using multiple treatment comparison methods. The utility estimates associated with health states of ulcerative colitis patients were obtained from the literature. Resource use and drug use frequencies as well as unit costs were obtained from Dutch sources. The primary effectiveness measure used in the analysis was quality-adjusted life years (QALYs).
Results
For a typical UC patient with body weight of 70 kg, the costs of treatment with infliximab, cyclosporine, and surgery over a 1-year treatment period were €17,062, €14,784, €13,979, respectively. The associated numbers of QALYs were 0.80, 0.70, and 0.58 for infliximab, cyclosporine, and surgery respectively. The incremental cost-effectiveness ratio for infliximab was €24,277 per QALY gained compared to cyclosporine, and €14,639 per QALY gained compared to surgery.
Conclusions
Infliximab induction regimen appears to be a cost-effective treatment option in comparison to cyclosporine and surgery for hospitalized patients with acute exacerbations of UC, refractory to intravenous corticosteroids in the Netherlands.
doi:10.1007/s13554-012-0007-0
PMCID: PMC3873082  PMID: 24392304
Colectomy; Cost-effectiveness; Cyclosporine; Gastroenterology; Infliximab; The Netherlands; Ulcerative colitis
6.  Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn’s disease 
Gut  2004;53(1):70-77.
Background and aims: To verify whether targeting defective mucosal T cell death underlies the sustained therapeutic benefit of infliximab in Crohn’s disease, we explored its in vivo proapoptotic effect after 10 weeks of treatment, and its in vitro killing activity on lamina propria T cells (LPT) and peripheral blood T cells (PBT), both isolated from Crohn’s disease patients.
Methods: Endoscopic intestinal biopsies were collected from 10 Crohn’s disease patients (six steroid refractory and four fistulising) before and after three consecutive infusions of infliximab, administered at week 0, 2, and 6 in a single intravenous dose (5 mg/kg), and from 10 subjects who proved to have functional diarrhoea. Apoptosis was determined in vivo by TUNEL assay, and in vitro by fluorescein isothiocyanate-annexin V/propidium iodide staining on LPT and PBT from Crohn’s disease patients cultured with infliximab. The effect of the broad caspase inhibitor Z-VAD-FMK and the neutralising anti-Fas antibody ZB4 was tested in vitro on LPT and PBT treated with infliximab. Caspase-3 activity was determined by immunoblotting.
Results: In Crohn’s disease patients, infliximab treatment induced a sustained LPT apoptosis, still evident four weeks after the last infusion. In vitro infliximab induced death of LPT from Crohn’s disease patients occurred via apoptosis rather than necrosis. LPT showed a higher susceptibility to infliximab induced apoptosis than PBT in Crohn’s disease patients. The signalling pathway underlying the restoration of infliximab induced LPT apoptosis occurred via the caspase pathway but not Fas-Fas ligand interaction in Crohn’s disease.
Conclusions: These findings demonstrate that apoptosis is the major mechanism by which infliximab exerts its killing activity on LPT in Crohn’s disease. The sustained LPT proapoptotic action of infliximab, which extends far beyond its circulating half life, may be responsible for the sustained remission induced in Crohn’s disease patients by infliximab retreatment.
PMCID: PMC1773915  PMID: 14684579
apoptosis; Crohn’s disease; infliximab; lamina propria T cells; caspase-3
7.  Changes in inflammation and quality of life after a single dose of infliximab during on-going treatment: Differences between patients with and without IBD symptoms at time of administration 
Background
Infliximab is used increasingly as maintenance therapy for inflammatory bowel disease (IBD); however the effects of a single maintenance dose of infliximab are unclear with respect to quality of life and hormones related to growth and puberty.
Objective
Determine the time course of inflammatory, hormonal and quality-of-life changes following a single dose of infliximab in the context of on-going therapy, as related to presence of IBD symptoms at time of administration.
Methods
Children and adolescents with IBD receiving on-going therapy with infliximab for clinical indications were recruited. Pediatric Crohn’s Disease Activity Index (PCDAI) was determined at baseline and laboratory measures of hsCRP and hormones of growth and puberty were determined on Days 0, 2 and 14. IBD-related quality of life (IMPACT-III questionnaire) was tested on Days 0 and 14. Subjects who had symptoms of IBD were compared to asymptomatic subjects.
Results
Subjects overall and in the symptomatic group exhibited improved hsCRP by Day 2 following treatment. Symptomatic subjects had higher PCDAI scores and lower quality-of-life scores than asymptomatic subjects on Day 0, while at Day 14 there were no significant differences in quality-of-life scores between the two groups.
Conclusions
Even in the context of on-going treatment, a single dose of infliximab results in decreased hsCRP an improvement that is particularly noted among subjects who are symptomatic at the time of treatment. While randomized trials are needed, these observational data may assist clinicians, patients and families regarding expectations about timing and extent of these changes following a single treatment dose.
doi:10.1097/MPG.0b013e3182382ee3
PMCID: PMC3297691  PMID: 21946833
Inflammatory bowel disease; infliximab; inflammation; quality of life; adolescent
8.  Medical management of inflammatory bowel disease among Canadian gastroenterologists 
Despite recent advancements in the understanding of the pathogenesis of inflammatory bowel disease (IBD) and the development of therapeutic agents to treat it, the complications of IBD are significant contributors to morbidity, decreased quality of life and economic burden in terms of hospitalizations, resource use and time away from work. To date, biological agents, such as infliximab – a tumour necrosis factor-alpha monoclonal antibody – have proven to be the most effective therapeutic agents; however, little research investigating how clinicians use biologicals in clinical practice has been conducted. This study aimed to describe the clinical practice patterns of infliximab use among Canadian physicians for the treatment of medically refractory IBD and, furthermore, investigated several factors possibly influencing these patterns.
BACKGROUND:
Little is known about physician perceptions of and practices in using infliximab – a biological agent that was approved in Canada for the treatment of Crohn’s disease in 2001, and for ulcerative colitis in 2006.
OBJECTIVES:
To describe Canadian gastroenterologists’ use and perceptions of infliximab in the treatment of refractory inflammatory bowel disease (IBD), and to identify factors that may influence a gastroenterologist’s decision to initiate infliximab therapy.
METHODS:
A postal questionnaire was distributed to all practicing clinicians captured in the 2007 membership of the Canadian Association of Gastroenterology. Each physician was contacted up to a maximum of three times.
RESULTS:
Of 466 questionnaires mailed out, responses were received from 336 (72%), with 292 respondents (63%) returning fully completed surveys. For 80% of respondents, IBD patients comprised less than 30% of their clinical practice. Most prescribed infliximab at an initial dose of 5 mg/kg (97%), prescribed loading doses at 0, 2 and 6 weeks (88%), premedicated with corticosteroids (74%), administered maintenance infusions at eight-week intervals (89%), co-administered immunosuppressive agents (81%) and continued infliximab ‘indefinitely’ as long as it was effective and well tolerated (76%). Most gastroenterologists (>70%) identified lack of drug insurance coverage and provincial funding criteria as important barriers to prescribing infliximab.
CONCLUSIONS:
Most Canadian gastroenterologists exhibited similar practice patterns with respect to the use of infliximab for induction and maintenance therapy of IBD. Common barriers to the initiation of infliximab therapy were identified.
PMCID: PMC3206553  PMID: 22059162
Inflammatory bowel diseases; Infliximab; Treatment
9.  Are we giving azathioprine too late? The case for early immunomodulation in inflammatory bowel disease 
Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).
doi:10.3748/wjg.14.5512
PMCID: PMC2746337  PMID: 18810768
Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Immunosuppressants; Azathioprine
10.  Serial intralesional injections of infliximab in small bowel Crohn’s strictures are feasible and might lower inflammation 
Background
Crohn’s disease can cause strictures throughout the gastrointestinal tract. Endoscopic balloon dilatation is a well-established treatment, but recurrence is seen in up to three out of four cases. Infliximab is playing an increasingly important role in the modern systemic treatment of severe Crohn’s disease. Combining the anti-inflammatory effects of infliximab with the proven effect of endoscopic balloon dilatation could possibly improve outcome. In small studies, intralesional injections in perianal fistulas have been effective and endoscopic injection therapy in colonic strictures is feasible.
Objective
We wanted to assess whether serial intralesional injection of infliximab in small bowel strictures is feasible and reduces local inflammation.
Methods
We included six patients with Crohn’s disease and inflammatory small bowel strictures. They were treated with endoscopic serial balloon dilatation. Subsequent to each dilatation, 40 mg infliximab was injected submucosally. A modified simplified endoscopic score for Crohn’s disease was used for the involved area before the initial treatment and at the final follow-up after six months. Complications and development of symptoms were registered.
Results
Balloon dilatation and serial injection of infliximab were accomplished in five out of six patients. One patient completed the serial balloon dilatations and follow-up but received only one infliximab injection. The modified simplified endoscopic score for Crohn’s disease decreased in all patients. There were no adverse events registered and all patients described themselves as feeling well.
Conclusions
Combining balloon dilatation of strictures with serial intralesional injection of infliximab in Crohn’s disease of the small bowel is feasible and seems successful in reducing inflammation.
doi:10.1177/2050640614547805
PMCID: PMC4212499  PMID: 25360319
Endoscopic balloon dilatation; Crohn’s disease; Double balloon enteroscopy; infliximab
11.  Long-term response rates to infliximab therapy for Crohn’s disease in an outpatient cohort 
BACKGROUND:
Infliximab’s efficacy in the induction and maintenance of remission in luminal Crohn’s disease has been confirmed by randomized, controlled trials. Less clearly described are long-term outcomes in the clinical practice setting since the establishment of regularly scheduled, every eight-week maintenance infliximab infusions. Existing reports describing clinical practice outcomes are limited by short durations of follow-up or by the use of episodic dosing, or focus on safety data rather than clinical outcomes.
OBJECTIVE:
To examine induction and maintenance responses to infliximab in an outpatient inflammatory bowel disease clinic.
METHODS:
A retrospective chart review was performed. Clinical outcomes were infliximab induction and maintenance responses, defined as the ability to stop and remain off corticosteroids while not requiring additional therapy for active disease.
RESULTS:
One hundred thirty-three patients were identified with records sufficiently detailed to be analyzed. Of these, 117 patients (88%) demonstrated a clinical response to induction; 104 of 117 (89%) were on concomitant immunosuppressive therapy; 80 of 104 on azathioprine/6-mercaptopurine (77%); and 24 of 104 on methotrexate (23%). The mean duration of clinical response was 94 weeks (95% CI 78.8 to 109.2). The proportion of patients who maintained response at 30 weeks was 83.2%, at 54 weeks was 63.6% and at 108 weeks was 44.9%. Adverse events occurred for 15 of 117 patients (12.8%), consisting of nine infusion reactions, four serum sickness-like reactions, one rash and one infection.
CONCLUSION:
Patients treated with infliximab therapy for luminal Crohn’s disease in our outpatient clinic achieved excellent induction and maintenance of response rates, confirming the real-life efficacy of maintenance infliximab established in clinical trials.
PMCID: PMC2706747  PMID: 19440565
Clinical practice; Crohn’s disease; Immunosuppression; Infliximab
12.  Long-term efficacy of infliximab maintenance therapy for perianal Crohn’s disease 
AIM: To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease (CD).
METHODS: Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s database. The activities of the perianal lesions were evaluated using the modified perianal CD activity index (mPDAI) score. The primary endpoint was a clinical response at 12-15 wk after surgery as a short-term efficacy. Secondary endpoints were recurrence as reflected in the mPDAI score, defined as increased points in every major element. The clinical responses were classified as completely healed (mPDAI = 0), partially improved (mPDAI score decreased more than 4 points), and failure or recurrence (mPDAI score increased or decreased less than 3 points).
RESULTS: There were 43 males and 19 females, of whom 26 were consecutively treated with infliximab after surgery as maintenance therapy. Complete healing was not seen. Failure was seen in 10/36 (27.8%) patients without infliximab and 4/26 (15.4%) patients with infliximab (P = 0.25). Partial improvement was seen in 26/36 (72.2%) patients without infliximab and 22/26 (88.5%) patients with infliximab (P = 0.25). Short-term improvement was achieved in 48/62 (77.4%) patients. Although the mPDAI score improved significantly with surgery regardless of infliximab, it decreased more from baseline in patients with infliximab (50.0%) than in those without infliximab (28.6%), (P = 0.003). In the long-term, recurrence rates were low regardless of infliximab in patients without anorectal stricture. In patients with anorectal stricture, cumulative recurrence incidences increased gradually and exceeded 40% at 5 years regardless of infliximab. No efficacy of infliximab treatment was found (P = 0.97). Although the cumulative rate of ostomy creation was also low in patients without stricture and high in patients with stricture, no protective efficacy was found with infliximab treatment (P = 0.6 without stricture, P = 0.22 with stricture).
CONCLUSION: Infliximab treatment was demonstrated to have short-term efficacy for perianal lesions. Long-term benefit with infliximab was not proven, at least in patients with anorectal stricture.
doi:10.3748/wjg.v17.i9.1174
PMCID: PMC3063910  PMID: 21448422
Crohn’s disease; Perianal fistula; Infliximab; Anorectal stricture; Long-term efficacy
13.  Contrast enhanced magnetic resonance imaging of the terminal ileum in children with Crohn’s disease 
Gut  2003;52(3):393-397.
Background and aims: Recently, magnetic resonance imaging (MRI) has been introduced in the diagnosis of patients with inflammatory bowel disease (IBD). However, it is still rarely reported in paediatric IBD. We studied the diagnostic value of gadolinium enhanced MRI in revealing inflammation of the distal ileum in children with Crohn’s disease (CD) and in differentiating them from patients with other inflammatory diseases of the gut. MRI was performed using a polyethylene glycol (PEG) solution as oral contrast agent to distend the small bowel (CE-PEG-MRI).
Subjects and methods: Seventy five consecutive patients (median age 13.6 years, range 8–17) with suspected CD underwent ileocolonoscopy with biopsy and CE-PEG-MRI. CD activity was measured by the paediatric Crohn’s disease activity index (PCDAI). CE-PEG-MRI was evaluated with an overall score calculated, taking into account both wall thickness and contrast enhancement.
Results: Active CD with distal ileitis was diagnosed in 26 cases, active ulcerative colitis (UC) in 18, and spondyloarthropathy and indeterminate ileocolitis in 11; 20 children served as controls. In all CD patients, CE-PEG-MRI revealed a marked ileal involvement with increased wall thickness and parietal contrast enhancement and showed a high concordance with endoscopy and histology, whereas the test was negative in all controls. Of the 18 UC patients, CE-PEG-MRI was negative in 15 and showed a mild parietal contrast enhancement of the terminal ileum in only three of seven patients with backwash ileitis. Among the group of spondyloarthropathy patients, six had mucosal erosions and five mild superficial ileitis: CE-PEG-MRI was negative in four and revealed only mild parietal contrast enhancement of the ileal wall in seven. CE-PEG-MRI did not show an increase in wall thickness of the distal ileum in any of the UC or spondyloarthropathy patients. The sensitivity and specificity of CE-PEG-MRI related to the presence of erosive ileitis, as documented by endoscopy, were 84% and 100%, respectively. In addition, the test correlated markedly with endoscopy and histology in the entire population (r=0.94; r=0.95, respectively) as well as with the PCDAI in CD patients (r=0.91).
Conclusions: In children with active CD, CE-PEG-MRI is a very sensitive and specific test for the detection of distal ileitis and for differentiation from other inflammatory diseases of the gut. The test could also be useful for the firstline diagnostic approach in children with suspected CD. The high correlation of CE-PEG-MRI with ileal endoscopy and histology as well as with PCDAI makes this test of great interest for future studies as a tool for monitoring the clinical course and the effect of therapy in CD patients.
PMCID: PMC1773565  PMID: 12584222
Crohn’s disease; magnetic resonance imaging; spondyloarthropathy; ulcerative colitis
14.  Adalimumab for orbital myositis in a patient with Crohn’s disease who discontinued infliximab: a case report and review of the literature 
BMC Gastroenterology  2013;13:59.
Background
Orbital myositis is a rare extra-intestinal manifestation of inflammatory bowel disease. Seventeen cases of Crohn’s disease associated orbital myositis and 3 cases of ulcerative colitis associated orbital myositis have been reported in the published literature since 1970. We report the use of adalimumab (Abbott, Canada, Inc.) for orbital myositis in a patient with Crohn’s disease who discontinued infliximab (Janssen, Canada, Inc.) and review of the published literature.
Case presentation
A 35 year-old male with a 7-year history of Crohn’s disease was treated with an ileocolonic resection and re-anastomosis followed by infliximab which maintained full endoscopic and clinical remission for four years. After stopping the infliximab for infusion-related reactions he presented with 3-day history of severe right eye pain, pain with ocular movement, proptosis, and conjunctival injection. He had no intestinal symptoms and endoscopic assessment revealed no active luminal disease. CT of the orbit revealed an enlarged right medial rectus muscle with tendonous involvement and a diagnosis of orbital myositis was made. Treatment with 80 mg per day prednisone with tapering dose and adalimumab, induction and maintenance, resulted in rapid resolution of the orbital myositis and ocular symptoms with no recurrences on follow-up at 10 months.
Conclusions
The current case demonstrates a rare extraintestinal manifestation of Crohn’s disease, orbital myositis, and its temporal relationship to the discontinuance of infliximab therapy and its successful treatment, without recurrence with tapering prednisone and adalimumab.
doi:10.1186/1471-230X-13-59
PMCID: PMC3621100  PMID: 23556424
Crohn’s disease; Ulcerative colitis; Orbital myositis; Extraintestinal manifestations; Inflammatory bowel disease; Infliximab; Adalimumab
15.  Infliximab Dosing Patterns in a Sample of Patients with Crohn's Disease: Results from a Medical Chart Review 
Background
Infliximab, a monoclonal antibody tumor necrosis factor-alpha inhibitor, is an effective therapy that is indicated for the treatment of patients with Crohn's disease. Although dose escalation from 5 mg/kg to 10 mg/kg is allowed according to the prescribing label of infliximab, conflicting results exist regarding the rate at which this escalation may occur, which may affect payers and providers.
Objective
The goal of this exploratory study was to characterize and quantify the rate of infliximab dose escalation in a sample of patients with Crohn's disease.
Methods
Administrative claims data from patients with Crohn's disease in a large mid-Atlantic managed care organization were collected and used to target and recruit providers into a chart review study of infliximab dosing. Data from the charts of 161 patients with Crohn's disease who were receiving infliximab between 2006 and 2010 were extracted. Patients were grouped into an infliximab dose-escalation group or a dose-stable group based on these data. The evidence of any infliximab dose ≥7.5 mg/kg or evidence of a mean maintenance interval of 42 days or less resulted in the placement of a patient in the dose-escalation group, with the balance of patients comprising the stable-dose group.
Results
A total of 925 infliximab infusions were captured from 161 patients. Of the 161 patients identified, 110 had at least 4 infusions, and 4 had missing data; therefore, only 106 (66%) patients were qualified for the final infliximab dosing analysis. A total of 18 (17%) of these patients had evidence of infliximab dose escalation (dose-escalation group), and the remaining 88 (83%) patients had a consistent 5-mg/kg dose and schedule (stable-dose group). Of the 18 patients in the dose-escalation group, 9 (50%) had a decrease in maintenance interval, whereas 12 (66.7%) patients had an increase in their dosage. A total of 3 (16.7%) patients had both an increase in dose and a reduction in maintenance interval.
Conclusions
Infliximab has been shown to be a cost-effective treatment for patients with Crohn's disease. The rate of infliximab dose escalation in this study was within the lower range of published estimates for this medication. Studies using larger sample sizes are needed to validate the findings of the current study. In addition, studies that are focused on quantifying and describing the nature of infliximab dose escalation may be useful in the development of successful patient–treatment matching algorithms.
PMCID: PMC4049116  PMID: 24991393
16.  Mucosal Healing in Inflammatory Bowel Disease—A True Paradigm of Success? 
Gastroenterology & Hepatology  2012;8(1):29-38.
Mucosal healing is gaining more acceptance as a measure of disease activity in Crohn's disease and ulcerative colitis, and it is also gaining acceptance as an endpoint in clinical trials. Recent publications have correlated achievement of mucosal healing with good outcomes. Currently, there is no validated definition of what constitutes mucosal healing in inflammatory bowel disease. In clinical trials of ulcerative colitis, mucosal healing has been achieved with 5-aminosalicylates, corticosteroids, azathioprine, and infliximab. For Crohn's disease, mucosal healing has been achieved with corticosteroids, infliximab, and adalimumab, and mucosal healing has been maintained with infliximab. Achievement of long-term mucosal healing has been associated with a decreased risk of colectomy and colorectal cancer in ulcerative colitis patients, a decreased need for cortico-steroid treatment in Crohn's disease patients, and a trend toward a decreased need for hospitalization in Crohn's disease patients. Unfortunately, assessment of mucosal healing requires regular use of endoscopy, which is associated with increased costs, patient discomfort, and side effects. Biomarkers such as fecal calprotec-tin, fecal lactoferrin, serum C-reactive protein, and fecal S1 00A1 2 have been shown to correlate with disease activity in ulcerative colitis and Crohn's disease; in the future, these biomarkers might be used as surrogate markers for mucosal healing. Newer clinical trials are incorporating mucosal healing as an endpoint for evaluation of efficacy. However, before mucosal healing will be sufficient to guide therapy, clinicians need a standard definition of mucosal healing and a consistently used, prospectively validated scale with good interobserver agreement.
PMCID: PMC3277196  PMID: 22347830
Mucosal healing; ulcerative colitis; Crohn's disease; anti—tumor necrosis factor agents; corticosteroids; colonoscopy
17.  The impact of infliximab treatment on quality of life in patients with inflammatory rheumatic diseases 
In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and 24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab and placebo groups was similar in the AS (10.1, 9.2–11.0), PsA (8.6, 7.8–9.4), and RA (10.1, 9.2–11.0) cohorts. Patients with RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those in the placebo group with an effect size of 4.6 (4.2–5.1) in RA and 2.7 (2.4–3.1) in PsA. Patients in large randomized controlled studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly greater improvement in HRQoL after treatment with infliximab.
doi:10.1186/ar2306
PMCID: PMC2212571  PMID: 17922913
18.  Surgery for Crohn’s disease in the era of biologicals: A reduced need or delayed verdict? 
Crohn’s disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. Ultimately, up to 70% of all patients will need surgery, despite optimized medical therapy. Moreover, about half of the patients will need redo-surgery because of disease recurrence. The introduction of anti-tumor necrosis factor (TNF) drugs (Infliximab in 1998) revolutionized the treatment of CD. Different randomized trials assessed the efficacy of anti-TNF treatment not only to induce, but also to maintain, steroid-free remission. Furthermore, these agents can rapidly lead to mucosal healing. This aspect is important, as it is a major predictor for long-term disease control. Subgroup analyses of responding patients seemed to suggest a reduction in the need for surgery at median-term follow up (1-3 years). However if one looks at population surveys, one does not observe any decline in the need for surgery since the introduction of Infliximab in 1998. The short follow-up term and the exclusion of patients with imminent surgical need in the randomized trials could bias the results. Only 60% of patients respond to induction of anti-TNF therapy, moreover, some patients will actually develop resistance to biologicals. Many patients are diagnosed when stenosing disease has already occurred, obviating the need for biological therapy. In a further attempt to change the actual course of the disease, top down strategies have been progressively implemented. Whether this will indeed obviate surgery for a substantial group of patients remains unclear. For the time being, surgery will still play a pivotal role in the treatment of CD.
doi:10.3748/wjg.v18.i29.3828
PMCID: PMC3413054  PMID: 22876034
Crohn’s disease; Surgery; Biological agents; Anti-tumor necrosis factor drugs; Remission
19.  The impact of biologics on health-related quality of life in patients with inflammatory bowel disease 
Background:
Inflammatory bowel disease (IBD) is characterized by a chronic relapsing inflammation of the gastrointestinal tract. Adult IBD patients suffer from a disabling disease which greatly affects health-related quality of life (HRQoL). A worse HRQoL in these patients may result in a defensive and ineffective use of medical attention and thus higher medical costs. Because of its chronic nature, IBD may also cause psychological problems in many patients which may also influence HRQoL and care-seeking behavior. An important factor reducing HRQoL is disease activity. Induction of remission and long-term remission are important goals for improving HRQoL. Furthermore, remission is associated with a decreased need for hospitalization and surgery and increased employment, which in turn improve HRQoL. Treatment strategies available for many years are corticosteroids, 5-aminosalicylates and immunnosuppressants, but these treatments did not show significant long-term improvement on HRQoL. The biologics, which induce rapid and sustained remission, may improve HRQoL.
Objective:
To review and evaluate the current literature on the effect of biologics on HRQoL of IBD patients.
Methods:
We performed a MEDLINE search and reviewed the effect of different biologics on HRQoL. The following subjects and synonyms of these terms were used: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, quality of life, health-related quality of life, fatigue, different anti-TNF medication, and biologicals/biologics (MESH). Studies included were limited to English-language, adult population, full-text, randomized, double-blind, placebo-controlled in which HRQoL was measured.
Results:
Out of 202 identified articles, 8 randomized controlled trials (RCT) met the inclusion criteria. Two RCTs on infliximab showed significant improvement of HRQoL compared to placebo which was sustained over the long term. One RCT on adalimumab showed a significant and sustained improvement of HRQoL compared to placebo. This study showed also significant decrease of fatigue in the adalimumab-treated patients. Three RCTs on certolizumab showed a significant improvement of HRQoL in the intervention group compared to placebo. Two RCTs of natalizumab treatment were found. One study showed significant and sustained improvement compared to placebo, and also scores of HRQoL comparable to that in the general population, but in the other no significant results were found.
Conclusion:
The biologics infliximab, adalimumab, certolizumab, and natalizumab demonstrated significant improvement of HRQoL of IBD patients compared with placebo. However, we found differences in improvement of HRQoL between the different biologics.
PMCID: PMC3108643  PMID: 21694833
inflammatory bowel disease; health-related quality of life; health care costs; biologics
20.  Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease 
Gut  2002;50(2):206-211.
Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn's disease. Because Crohn's disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes.
Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn's disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab.
Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn's disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells.
Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn's disease.
PMCID: PMC1773100  PMID: 11788561
apoptosis; T lymphocytes; Crohn's disease; infliximab; tumour necrosis factor
21.  Risk Factors for Surgical Recurrence after Ileocolic Resection of Crohn’s Disease 
Diseases of the colon and rectum  2008;51(8):1211-1216.
PURPOSE
We evaluated the effect of potential clinical factors on surgical recurrence of ileal Crohn’s disease after initial ileocolic resection.
METHODS
One hundred seventy-six patients with ileal Crohn’s disease who underwent an ileocolic resection with anastomosis were identified from our database. The outcome of interest was time from first to second ileocolic resection. Survival analysis was used to assess the significance of the Montreal phenotype classification, smoking habit, a family history of inflammatory bowel disease and other clinical variables.
RESULTS
In our final Cox model, a family history of inflammatory bowel disease (hazard ratio 2.24, 95 percent confidence interval 1.16–4.30, P=0.016), smoking at time of initial ileocolic resection (hazard ratio 2.08, 95 percent confidence interval 1.11–3.91, P=0.023) was associated with an increased risk of a second ileocolic resection while postoperative prescription of immunomodulators (hazard ratio 0.40, 95 percent confidence interval 0.18–0.88, P= 0.022) was associated with a decreased risk of a second ileocolic resection.
CONCLUSIONS
Both a family history of inflammatory bowel disease and smoking at the time of the initial ileocolic resection are associated with an increased risk of a second ileocolic resection. Postoperative prescription of immunomodulators is associated with a reduced risk of surgical recurrence. This study supports the concept that both genetic and environmental factors influence the risk of surgical recurrence of ileal Crohn’s disease.
doi:10.1007/s10350-008-9348-7
PMCID: PMC2580671  PMID: 18536967
Crohn’s disease; Ileocolic resection; Postoperative recurrence
22.  Coexisting Crohn's Disease and Takayasu's Arteritis in Two Patients Treated with Anti-TNF-α Therapies 
Crohn's disease (CD) and Takayasu's arteritis (TA) are inflammatory granulomatous autoimmune disorders. Simultaneous occurrence of CD and TA in the same individual is rare. We report two cases treated with biologic agents. Case 1: A 16-year-old male presented with abdominal pain, nausea, vomiting. CT angiogram showed thickening of the terminal ileum, wall thickening and narrowing of multiple large and medium arteries including aorta and left common carotid. Colonoscopy with biopsy of the stenotic ileocecal valve confirmed CD. Resected carotid artery pathology was consistent with TA. Treatment was initially begun with prednisone, then methotrexate was started followed by infliximab. Due to side effects, methotrexate was switched to azathioprine. He remained asymptomatic. Case 2: A 38-year-old male with well-characterized Crohn's ileocolitis for 15 years, who had been treated with prednisone, mesalamine, sulfasalazine, and azathioprine presented with chest, upper back and abdominal pain. CT angiogram showed vasculitis of large and medium arteries, with stenosis of the right renal artery, and wall thickening of the sigmoid colon. He was diagnosed with TA. He underwent treatment with infliximab and adalumimab on different occasions, which were later discontinued due to fever, bacteremia and complications from sepsis. He remained on prednisone and azathioprine. In these two patients with both CD and TA the diagnoses were confirmed by imaging and pathologic findings. Both patients developed vascular complications. Tumor necrosis factor inhibitor therapy was effective in one patient but discontinued in the other due to infection. Further research into the association of CD and TA may provide clues to their etiologies and guide effective interventions.
doi:10.1159/000270919
PMCID: PMC2988895  PMID: 21103225
Crohn's disease; Takayasu's arteritis; Coexisting; Anti-TNF alpha
23.  Crohn's disease 
Clinical Evidence  2011;2011:0416.
Introduction
Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty.
Key Points
Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae.The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity.
First-line treatment to induce remission of acute disease is corticosteroids. Budesonide is generally recommended in mild to moderate ileocaecal disease because it is only slightly less effective in inducing remission than prednisolone and has a superior adverse-effect profile.Prednisolone or methylprednisolone are generally recommended for severe or more extensive disease because of their superior efficacy.
Azathioprine and mercaptopurine are effective in inducing remission and healing fistulae in Crohn's disease, provided that at least 17 weeks of treatment are given. Monitoring for myelosuppression is obligatory. Aminosalicylates (mesalazine, sulfasalazine) may reduce disease activity, but we don't know which regimen is best to induce remission. Methotrexate 25 mg weekly increases remission rates and has a corticosteroid-sparing effect. There is consensus that it is also effective for maintenance.Infliximab (a cytokine inhibitor) is effective in inducing and maintaining remission in Crohn's disease, but the long-term adverse-effect profile is unclear; infliximab is therefore generally reserved for treatment of disease that is refractory to treatment with corticosteroids or other immunomodulators. Antibiotics and ciclosporin are unlikely to be beneficial in inducing remission.
Bowel-sparing surgery to induce remission may be preferable to extensive resection, to avoid short-bowel syndrome. Segmental and sub-total colectomy have similar remission rates.
Laparoscopic resection may reduce postoperative hospital stay, but we don't know whether strictureplasty is effective.
Azathioprine has been shown to be beneficial in maintaining remission in Crohn's disease, either alone or after surgery, and has a corticosteroid-sparing effect, but it is associated with important adverse effects. Ciclosporin, or oral corticosteroids, alone are unlikely to be beneficial in maintaining remission after medical treatment. Methotrexate and infliximab may also maintain remission compared with placebo. Smoking cessation reduces the risk of relapse, and enteral nutrition may be effective. Fish oil and probiotics have not been shown to be effective.
Mesalazine seems effective in maintaining medically induced remission, but we don't know how effective other aminosalicylates are in maintaining remission.
PMCID: PMC3217808  PMID: 21524318
24.  Recurrent pneumonia and colobronchial fistula from Crohn’s disease: Infliximab alters and simplifies surgical management 
Annals of Gastroenterology  2012;25(4):361-364.
We report a rare case of right-sided colobronchial fistula in a 47-year-old, severely malnourished male with a history of regional enteritis and recurrent right lower and middle lobe pneumonias medically managed with the addition of the immunomodulator infliximab prior to surgery. On admission, evaluation of sputum cultures and chest radiograph pattern of pneumonia led to the suspicion of colobronchial fistula. This diagnosis was confirmed by abdominal CT enteroclysis. This patient’s pneumonia was initially treated with empiric antibiotics, then focused antibiotics based on culture results. The treatment for the regional enteritis and the secondary colobronchial fistula consisted of immunosuppression with infliximab, bowel rest, and total parenteral nutrition. The patient was discharged on a limited course of prednisone and received maintenance therapy with 3mg/kg IV infliximab infusions for four additional treatments with dramatic improvement in his clinical condition. Surgical therapy consisted of only bowel resection; no thoracic surgery or lung resection was necessary. The patient has had a dramatic improvement in his clinical condition and is currently disease-free on no maintenance therapy. The use of TNF-blocking agents such as infliximab may simplify the surgical approach in patients with complicated fistulous Crohn’s disease.
PMCID: PMC3959410  PMID: 24714263
Crohn’s disease; infliximab; colobronchial fistula
25.  Health care resource use and costs for Crohn’s disease before and after infliximab therapy 
BACKGROUND:
Infliximab therapy in patients with Crohn’s disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study.
METHODS:
A retrospective analysis of economic data one and two years before and after infliximab therapy was performed using patients who served as their own controls. Total health care resource use and direct health care costs were compared for patients with or without fistulae.
RESULTS:
Patients with one (n=66) and two (n=39) years of economic data before and after infliximab treatment had their resource use and direct health care costs estimated. In the year following initiation of infliximab therapy, there were significant decreases in health care use, reflected in total hospital days (495 to 155 [P<0.05]), inpatient colonoscopies (46 to 24 [P<0.05]), outpatient colonoscopies (58 to 33 [P<0.05]) and major surgeries (10 to 2 [P<0.05]). Direct health care costs of inpatient costs for luminal (−$1,747 [P<0.05]) and fistulizing disease (−$2,530 [P<0.05]), major surgeries (−$1240 [P<0.05]) and outpatient colonoscopies (−$184 [P<0.05]) were also significantly reduced before and after infliximab therapy. Total direct health care costs, including the drug cost of infliximab, increased ($21,416 [P<0.05]). In general, the trends in health care costs analyzed over four consecutive years paralleled the two consecutive-year analysis.
CONCLUSIONS:
Infliximab therapy in patients with Crohn’s disease resulted in a significant decrease in both resource use and health care costs, but an increase in total direct health care costs once the cost of infliximab was added.
PMCID: PMC3202357  PMID: 21912761
Crohn’s disease; Economic analysis; Health care cost; Health policy; Inflammatory bowel disease; Infliximab

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