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Hans H Herfarth,
Jeffry A Katz, Stephen B Hanauer,
William J Sandborn,
Edward V Loftus,
Bruce E Sands,
Joseph A Galanko,
Dolly Walkup,
Kim L Isaacs,
Christopher F Martin,
Robert S Sandler,
Ryan B Sartor
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ABSTRACT: BACKGROUND:: The commensal bacterial flora plays a critical role in the postoperative recurrence of Crohn's disease (CD). We conducted a randomized, double-blind, placebo-controlled 6-month pilot trial of ciprofloxacin for the prevention of endoscopic recurrence in patients with CD who underwent surgery. METHODS:: Thirty-three patients with CD, who had undergone surgery with ileocolonic anastomosis within the previous 2 weeks, were randomized to treatment with ciprofloxacin (500 mg twice daily) or placebo tablets for 6 months. Endpoints were endoscopic recurrence at 6 months and safety and tolerability of long-term ciprofloxacin therapy. RESULTS:: Thirty-three patients were randomized; 14 patients discontinued the study early. Significant endoscopic recurrence was observed in 3 of 9 patients (33%) in the ciprofloxacin group and 5 of 10 patients (50%) in the placebo group at 6 months after surgery (P < 0.578). The intention-to-treat analysis demonstrated endoscopic recurrence in 11 of 17 patients (65%) in the ciprofloxacin group and 11 of 16 patients (69%) in the placebo group at month 6 (P < 0.805). Thirty-six adverse events occurred in 19 of 33 patients (58%). Possible drug-associated adverse events occurred significantly more often in the ciprofloxacin group (P < 0.043), leading to study drug discontinuation in 24% (4 of 17) and 6% of patients (1 of 16) in the ciprofloxacin and placebo groups, respectively (P < 0.166). CONCLUSIONS:: In this pilot study, ciprofloxacin was not more effective than placebo for the prevention of postoperative recurrence in patients with CD. Long-term ciprofloxacin therapy is limited by drug-associated side effects. Future studies in postoperative prevention of CD should evaluate antibiotic approaches with a more favorable safety profile.
Inflammatory Bowel Diseases 03/2013; · 4.86 Impact Factor
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ABSTRACT: : Natalizumab is an efficacious agent for the induction and maintenance of remission in patients with Crohn's disease (CD) who have failed anti-tumor necrosis factor (TNF) agents. We aimed to assess the efficacy and safety of natalizumab outside of clinical trial at a US tertiary center.
: Retrospective case review of patients with CD receiving natalizumab.
: Forty-nine patients with CD (28 women; median age, 33 years) receiving natalizumab from April 2008 to November 2011 were identified. Median duration of disease was 180 months (range, 36-576 months); 40 patients had ileocolonic disease, 1 had ileal disease, and 8 had colonic disease. Twenty-one patients had penetrating disease, and 28 had a history of CD-related surgical treatment. Forty-seven patients previously failed treatment with at least 1 anti-TNF agent. Median duration of natalizumab treatment was 7 months (interquartile range, 3-21.5 months). Twenty-four patients (49%) were continuing natalizumab at the time of this review, and 25 discontinued treatment because of the lack of response, side effects, or positive JC virus antibody. Seventeen patients (35%) successfully continued treatment with natalizumab for longer than 12 months, and nonpenetrating disease phenotype was identified as a predictor of longer response (compared with penetrating phenotype; P = 0.013). Nine patients (18.4%) experienced adverse effects, 5 of which were serious, but no case of progressive multifocal leukoencephalopathy occurred.
: This is the largest series of natalizumab-treated patients with CD. Our results show that natalizumab is an efficacious and safe treatment agent for patients refractory to anti-TNF agents and that nonpenetrating disease phenotype has more durable response over time.
Inflammatory Bowel Diseases 03/2013; 19(3):621-6. · 4.86 Impact Factor
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ABSTRACT: BACKGROUND:: The clinical utility of cellular therapies is being investigated in a broad range of therapeutic areas. This phase 1 study represents the first exploration of PDA001, a preparation of cells cultured from human placental tissue, in subjects with Crohn's disease. METHODS:: Twelve subjects with active, moderate-to-severe Crohn's disease unresponsive to previous therapy were given 2 intravenous infusions of PDA001 1 week apart, monitored weekly for 5 weeks, and assessed at 6 months, 1 year, and 2 years after infusion. Six subjects received 2 infusions of 2 × 10 cells (low dose), and 6 subjects received 2 infusions of 8 × 10 cells (high dose). RESULTS:: Mean baseline Crohn's Disease Activity Index in the low-dose and high-dose groups was 305 and 364, respectively, and mean C-reactive protein was 8 mg/L and 49 mg/L, respectively. All subjects in the low-dose group achieved a clinical response (a Crohn's Disease Activity Index decrease of ≥70 points versus baseline), and 3 achieved remission (a Crohn's Disease Activity Index decrease of ≥100 to <150 points). Two subjects in the high-dose group achieved response, and none met remission criteria. Most adverse events were mild to moderate in severity and included headache, nausea, fever, and infusion site reactions. CONCLUSIONS:: PDA001 infusions appear safe and well-tolerated in subjects with treatment-resistant Crohn's disease. A response was seen in all subjects in the low-dose group. The high-dose group, with a higher baseline disease activity, had only 2 responders, suggesting a more treatment-resistant population. A phase 2 study in this patient population is ongoing.
Inflammatory Bowel Diseases 02/2013; · 4.86 Impact Factor
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Gil Y Melmed,
Corey Allan Siegel,
Brennan M Spiegel,
John I Allen,
Robert Cima,
Jean-Frederic Colombel,
Themistocles Dassopoulos,
Lee A Denson,
Sharon Dudley-Brown,
Andrew Garb, Stephen B Hanauer,
Michael D Kappelman,
James D Lewis,
Isabelle Lynch,
Amy Moynihan,
David T Rubin,
R Balfour Sartor,
Ronald M Schwartz,
Douglas C Wolf,
Thomas A Ullman
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ABSTRACT: INTRODUCTION:: Variation in adherence to management guidelines for inflammatory bowel disease (IBD) suggests variable quality of care. Quality indicators (QIs) can be developed to measure the structure, processes, and outcomes of health care delivery. The RAND/UCLA appropriateness method was used to develop a set of process and outcome QIs to define quality of care for IBD. METHODS:: Guidelines and position papers for IBD published from 2006 to 2011 were reviewed for potential QIs, which were rated by a multidisciplinary panel. Potential process and outcome QIs were discussed at 3 moderated in-person meetings, with pre-meeting and post-meeting confidential electronic voting. Panelists rated the validity and feasibility of QIs on a 1 through 9 scale; disagreement was assessed using a validated index. QIs rated above 8 were selected for the final set. RESULTS:: More than 500 potential process QIs were extracted from guidelines. Following ratings and discussion by the first panel, 35 process QIs were selected for literature review. After the second panel, 10 process QIs were included in the final set. Candidate outcome QIs were then derived from physician, nurse, and patient input and ratings, in addition to outcomes associated with candidate process QIs. None of the top QIs exhibited disagreement. CONCLUSIONS:: A set of QIs for IBD was developed with expert interpretation of the literature and multidisciplinary input. Outcome QIs focused largely on remission and quality of life, whereas process QIs were aimed at therapeutic optimization and patient safety. Evaluation of these QIs in clinical practice is needed to assess the correlation of performance on process QIs with performance on outcome QIs.
Inflammatory Bowel Diseases 02/2013; · 4.86 Impact Factor
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Joel Pekow,
Urszula Dougherty,
Yong Huang,
Edward Gometz,
Jeff Nathanson,
Greg Cohen,
Shawn Levy,
Masha Kocherginsky,
Nanda Venu,
Maria Westerhoff,
John Hart,
Amy E Noffsinger, Stephen B Hanauer,
Roger D Hurst,
Alessandro Fichera,
Loren J Joseph,
Qiang Liu,
Marc Bissonnette
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ABSTRACT: BACKGROUND:: Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer. The standard method of surveillance for neoplasia in UC by colonoscopy is invasive and can miss flat lesions. We sought to identify a gene expression signature in nondysplastic mucosa without active inflammation that could serve as a marker for remote neoplastic lesions. METHODS:: Gene expression was analyzed by complementary DNA microarray in 5 normal controls, 4 UC patients without dysplasia, and 11 UC patients harboring remote neoplasia. Common gene ontology pathways of significantly differentially expressed genes were identified. Expression of genes which were progressively and significantly upregulated from controls to UC without neoplasia, to UC with remote neoplasia were evaluated by real-time polymerase chain reaction. Several gene products were also examined by immunohistochemistry. RESULTS:: Four hundred and sixty-eight genes were significantly upregulated, and 541 genes were significantly downregulated in UC patients with neoplasia compared with UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly upregulated from controls to nondysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increased expression of S100A9 and REG1α in UC-associated cancer and in nondysplastic tissue from UC patients harboring remote neoplasia compared with UC patients without neoplasia and controls. CONCLUSIONS:: Gene expression changes occurring as a field effect in the distal colon of patients with chronic UC identify patients harboring remote neoplastic lesions. These markers may lead to a more accurate and less invasive method of detection of neoplasia in patients with inflammatory bowel disease.
Inflammatory Bowel Diseases 02/2013; · 4.86 Impact Factor
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The American Journal of Gastroenterology 11/2012; 107(11):1622. · 7.28 Impact Factor
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Inflammatory Bowel Diseases 11/2012; 18(11):2001-3. · 4.86 Impact Factor
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William J Sandborn,
Christopher Gasink,
Long-Long Gao,
Marion A Blank,
Jewel Johanns,
Cynthia Guzzo,
Bruce E Sands, Stephen B Hanauer,
Stephan Targan,
Paul Rutgeerts,
Subrata Ghosh,
Willem J S de Villiers,
Remo Panaccione,
Gordon Greenberg,
Stefan Schreiber,
Simon Lichtiger,
Brian G Feagan
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ABSTRACT: In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown.
We evaluated ustekinumab in adults with moderate-to-severe Crohn's disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks.
The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P=0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P=0.03) and response (69.4% vs. 42.5%, P<0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab.
Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.).
New England Journal of Medicine 10/2012; 367(16):1519-28. · 53.30 Impact Factor
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Journal of Crohn s and Colitis 10/2012; · 2.57 Impact Factor
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ABSTRACT: BACKGROUND:: Ulcerative colitis (UC) is generally described as a superficial diffuse inflammation restricted to the colon and rectum. However, several case reports have described a distinct and rare type of UC-related pan-enteritis, typically occurring after colectomy. Corticosteroids are effective for induction of remission of this condition, but it is not clear how these patients should be managed long term. GOALS:: To further describe and define the entity of UC-related pan-enteritis and to investigate the efficacy of azathioprine for maintenance of remission. RESULTS:: We describe 5 patients with superficial diffuse ulcerative inflammation of the stomach, small bowel, and pouch if present. Four of the 5 patients developed enteritis after colectomy for ulcerative pancolitis. Pathology showed severe mucosal inflammation with infiltration of neutrophils and plasma cells from the stomach to the ileum. Video capsule endoscopy in 1 patient confirmed the presence of mucosal inflammation throughout the small bowel. All patients were started on a standardized treatment with intravenous corticosteroids for induction of remission and azathioprine for maintenance therapy. The conditions of all the patients rapidly improved, and subsequently, 4 patients were in full remission on azathioprine monotherapy, despite failure of this UC therapy before surgery, whereas 1 patient continues to have a steroid-dependent disease. CONCLUSIONS:: The outcomes of 5 cases of UC-related pan-enteritis as described in this report support a role for azathioprine in remission maintenance. Future research is needed to improve our understanding of this rare but distinct intestinal inflammatory disorder.
Journal of clinical gastroenterology 07/2012; · 2.21 Impact Factor
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Gastroenterology 07/2012; 143(3):e28; author reply e28-9. · 11.68 Impact Factor
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ABSTRACT: BACKGROUND: Thiopurines are the mainstay of conventional maintenance therapy in inflammatory bowel disease (IBD). Unfortunately, up to 50% of patients discontinue immunosuppressive therapy within 2 years due to intolerance or lack of efficacy. Allopurinol with low-dose thiopurine can optimize thiopurine metabolism for IBD patients with preferential shunting toward 6-methyl mercaptopurine (6-MMP) formation. The aim of this study was to assess long-term maintenance effectiveness and tolerability of allopurinol-thiopurine therapy in a larger multicenter cohort of IBD patients. METHODS: Enrolled patients who failed monotherapy with thiopurines due to a skewed metabolism were subsequently treated with a combination therapy of allopurinol and low-dose thiopurine. Adverse events were monitored and therapeutic adherence was assessed. Seventy-seven IBD patients were enrolled with a mean follow-up of 19 months. RESULTS: The median 6-thioguanine nucleotide concentration increased from 145 during monotherapy to 271 pmol/8 × 10(8) red blood cell (RBC) after at least 8 weeks of combination therapy while reducing the thiopurine dosage (P < 0.001). In contrast, median 6-MMP concentrations decreased from 10,110 to 265 pmol/8 × 10(8) RBC (P < 0.001). Leukopenia occurred in 12 patients (16%), requiring dose adaptation. Liver test abnormalities normalized in 81% of patients after the addition of allopurinol. Sixteen (21%) patients had to discontinue combination therapy. The percentage of patients still using combination therapy at 6, 12, 24, and 60 months was 87%, 85%, 76%, and 65%, respectively. CONCLUSIONS: Long-term combination therapy with allopurinol and low-dose thiopurines is an effective and well-tolerated treatment in IBD patients with a skewed thiopurine metabolism. (Inflamm Bowel Dis 2012;).
Inflammatory Bowel Diseases 05/2012; · 4.86 Impact Factor
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ABSTRACT: Patients with Crohn's disease and colonic inflammation that proves refractory to medical therapy often require a proctocolectomy and end ileostomy. Disease recurrence can occur despite creation of an end ileostomy and may lead to peristomal complications such as fistula formation, abscesses, stoma retraction, or strictures. We present the case of a 51-year-old man with medically refractory ileocolonic Crohn's disease who underwent a proctocolectomy with end ileostomy. The disease course was complicated by recurrence of ileal Crohn's disease despite biological therapy. The patient presented with peristomal complications including an enterocutaneous fistula, stoma retraction, and an ileal stricture necessitating surgical revision of the ileostomy. Review of literature confirms an approximately 30% risk of recurrence of Crohn's disease after an end ileostomy. A penetrating phenotype and preexisting ileal disease are risk factors for disease recurrence. A thorough evaluation of the stoma/peristomal area and evaluation of the small bowel by ileoscopy and small bowel imaging are required to assess the extent of disease and extraluminal complications such as stomal retraction and fistulas that require further surgical intervention. While postoperative medical treatment with immunosuppression or biological therapy is often employed, these therapies are unproven to prevent postoperative recurrence in the setting of a stoma.
Journal of wound, ostomy, and continence nursing: official publication of The Wound, Ostomy and Continence Nurses Society / WOCN 05/2012; 39(3):297-301. · 1.17 Impact Factor
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William J Sandborn,
Jean-Frederic Colombel,
Bruce E Sands,
Paul Rutgeerts,
Stephan R Targan,
Remo Panaccione,
Brian Bressler,
Karl Geboes,
Stefan Schreiber,
Richard Aranda,
Sheila Gujrathi,
Allison Luo,
Yun Peng,
Luisa Salter-Cid, Stephen B Hanauer
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ABSTRACT: The efficacy of abatacept, a selective costimulation modulator, in Crohn's disease (CD) and ulcerative colitis (UC) is unknown.
Four placebo-controlled trials evaluated the efficacy and safety of abatacept as induction (IP) and maintenance (MP) therapy in adults with active, moderate-to-severe CD (CD-IP; CD-MP) and UC (UC-IP1; UC-MP). In CD-IP and UC-IP1, 451 patients with CD and 490 patients with UC were randomized to abatacept 30, 10, or 3 mg/kg (according to body weight) or placebo, and dosed at weeks 0, 2, 4, and 8. In MP, 90 patients with CD and 131 patients with UC who responded to abatacept at week 12 in the induction trials were randomized to abatacept 10 mg/kg or placebo every 4 weeks through week 52.
In CD-IP, 17.2%, 10.2%, and 15.5% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at weeks 8 and 12, vs 14.4% receiving placebo (P = .611, P = .311, and P = .812, respectively). In UC-IP1, 21.4%, 19.0%, and 20.3% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at week 12, vs 29.5% receiving placebo (P = .124, P = .043, and P = .158, respectively). In CD-MP, 23.8% vs 11.1% of abatacept vs placebo patients were in remission at week 52. In UC-MP, 12.5% vs 14.1% of patients receiving abatacept vs placebo were in remission at week 52. Safety generally was comparable between groups.
The studies showed that abatacept is not efficacious for the treatment of moderate-to-severe CD or UC.
Gastroenterology 04/2012; 143(1):62-69.e4. · 11.68 Impact Factor
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Simon P L Travis,
Dan Schnell,
Piotr Krzeski,
Maria T Abreu,
Douglas G Altman,
Jean-Frédéric Colombel,
Brian G Feagan, Stephen B Hanauer,
Marc Lémann,
Gary R Lichtenstein,
Phillippe R Marteau,
Walter Reinisch,
Bruce E Sands,
Bruce R Yacyshyn,
Christian A Bernhardt,
Jean-Yves Mary,
William J Sandborn
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ABSTRACT: Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).
To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.
A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors.
There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR(2), Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity).
The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.
Gut 04/2012; 61(4):535-42. · 10.11 Impact Factor
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Yvette Leung,
Gil G Kaplan,
Kevin P Rioux,
James Hubbard,
Sarah Kamhawi,
Lidia Stasiak,
Russell D Cohen,
Shane M Devlin,
Remo Panaccione, Stephen B Hanauer,
David T Rubin
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ABSTRACT: Patients with Crohn's disease (CD) who smoke have a more complicated disease course.
Our primary objective was to assess smoking related variables that were associated with smoking cessation versus continued smoking in patients with CD.
A multi-center study identified CD patients who were seen at the University of Chicago and University of Calgary IBD clinics. Patients were categorized into three subgroups: lifetime non-smokers, current smokers, or ex-smokers. Participants completed questionnaires assessing their cigarette smoking behavior. Current smokers were prospectively followed for 6 months to assess smoking status and attempts to quit. Logistic regression analysis was performed to identify factors associated with smoking cessation.
Three hundred patients were enrolled with 148 identifying themselves as lifetime non-smokers, 70 as current smokers, and 82 as ex-smokers. Patients who reported their first cigarette within 5 min of waking were more likely to be current smokers (OR = 21; 95% CI 3.94-107.3) as compared to patients who waited greater than 60 min. Current smokers were more likely to have one or more household members who smoked compared to ex-smokers (P < 0.05). Nearly half (49%) of the current smokers were in the precontemplation stage of change (i.e. no intention to quit smoking). At the 6-month follow-up, only 11% reported they quit smoking.
Patients who report a short time to first cigarette in the morning may have more difficulty in smoking cessation. Current smokers were more likely to have another smoker in the household compared to ex-smokers. Current smokers had low levels of motivation to quit smoking and consequently with no intervention, very few quit 6 months after the baseline assessment.
Digestive Diseases and Sciences 02/2012; 57(4):1026-32. · 2.12 Impact Factor
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ABSTRACT: Ulcerative colitis (UC) is primarily a disease of non-smokers. Ex-smokers may have a more refractory disease course and anecdotal evidence in non-controlled clinical trials have suggested that smoking resumption, or the administration of nicotine, may ameliorate signs and symptoms of UC in ex-smokers. We report outcomes of ex-smokers with refractory UC who resumed low-dose cigarette smoking.
17 ex-smokers with refractory UC were identified. Clinical remission was defined as a disease activity index score of 0.
Two out of 17 patients refused the recommendation to resume smoking. Of the 15 patients who resumed smoking, the mean daily number of cigarettes was 8.6. Fourteen out of those 15 patients who resumed smoking were able to maintain prolonged clinical remission off steroids. One out of the 15 patients failed to improve and required oral steroids. Another patient was compelled to quit smoking since he became addicted. His disease flared after maintaining a prolonged remission of 3 years and he eventually underwent surgery. Three out of these 15 patients switched from cigarettes smoking to nicotine compounds and continued to maintain remission.
Resumption of low dose smoking in a selected group of ex-smokers with refractory UC may ameliorate signs and symptoms. Quality of life, medication side effects, and smoking risk factors should all be considered and discussed with patients. Smokers should be meticulously followed for compliance with "low-dose" regimen and all associated smoking risks.
Journal of Crohn s and Colitis 01/2012; 6(7):756-62. · 2.57 Impact Factor
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ABSTRACT: Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism. We discuss two brothers who were both diagnosed with ulcerative colitis (UC). Their disease remained active despite oral and topical mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully introduced for both patients and both were found to have high 6-MMP and low 6-TGN levels, despite normal TMPT enzyme activity, accompanied by transaminitis. Allopurinol was introduced in combination with MP dose reduction. For both brothers addition of allopurinol was associated with successful remission and optimized MP metabolites. These siblings with active UC illustrate that skewed thiopurine metabolism may occur despite normal TPMT enzyme activity and can lead to adverse events in the absence of disease control. We confirm previous data showing that addition of allopurinol can reverse this skewed metabolism, and reduce both hepatotoxicity and disease activity, but we now also introduce the concept of a family history of preferential MP metabolism as a clue to effective management for other family members.
Digestive Diseases and Sciences 12/2011; 57(1):250-3. · 2.12 Impact Factor
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ABSTRACT: Topical 5-aminosalicylates (5-ASAs) such as mesalamine are effective in inducing remission in patients with mild to moderately active ulcerative colitis (UC). However, there has been no meta-analysis of their efficacy in preventing relapse of quiescent UC.
We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials through July 2011 for randomized controlled trials comparing the effects of topical 5-ASAs with placebo in adults with quiescent UC. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity. The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Adverse events data were summarized.
The search identified 3061 citations; we analyzed data from seven (555 patients). All trials used mesalamine, but only one included patients with extensive disease. The duration of therapy ranged from 6-24 months. The RR of relapse of disease activity in patients with quiescent UC who were given topical mesalamine, compared with placebo, was 0.60 (95% confidence interval, 0.49-0.73; NNT = 3); there was no significant heterogeneity between studies (I(2) = 21%, P = .27). No significant differences in rates of adverse events rates were detected (RR = 1.01; 95% confidence interval, 0.59-1.72).
On the basis of a meta-analysis of 7 randomized controlled trials, topical mesalamine is effective in preventing relapse of quiescent UC, with no greater number of adverse events than placebo. However, because most studies included only patients with left-sided disease or proctitis, the efficacy of topical mesalamine in preventing relapse in patients with more extensive quiescent UC is not known.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 11/2011; 10(5):513-9. · 5.64 Impact Factor
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Inflammatory Bowel Diseases 08/2011; 18(5):809-11. · 4.86 Impact Factor
