Ulcerative Colitis: Hanauer S

Baron BW, Jeon HR, Glunz C, Peterson A, Cohen R, Hanauer S, Rubin D, Hart J, Baron JM. · Department of Pathology, The University of Chicago, Chicago, Illinois, USA. · J Clin Apher. · Pubmed #12494414 No free full text.

Abstract: The association of ulcerative colitis (UC) and thrombotic thrombocytopenic purpura (TTP) is rare. Only one prior patient with these two syndromes has been reported in the literature. In that case, splenectomy and proctectomy were performed to control the symptoms of TTP. We present two patients with UC who developed TTP and were successfully treated with multiple plasma exchanges (PEXs) in conjunction with medical therapy without the necessity for surgical intervention. Acquired TTP may be another extraintestinal autoimmune feature of UC. TTP in association with UC may be refractory to high-dose steroids and PEX, possibly requiring vincristine and splenectomy, as in the one previously reported case, to achieve remission.

Plevy S, Salzberg B, Van Assche G, Regueiro M, Hommes D, Sandborn W, Hanauer S, Targan S, Mayer L, Mahadevan U, Frankel M, Lowder J. · Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA. · Gastroenterology. · Pubmed #17920064 No free full text.

Abstract: BACKGROUND & AIMS: To evaluate the safety and biological activity of visilizumab (a humanized anti-CD3 monoclonal antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. METHODS: In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 microg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index <10 with a minimum decrease of 3 points; remission was <4 points. Endoscopic remission was a Mayo endoscopic subscore of 0 or 1. RESULTS: Eight patients received 15 microg/kg visilizumab. Because of dose-limiting toxicities (T-cell recovery >30 days in 2 of 8 patients), the dose was reduced to 10 microg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-microg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4(+) T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. CONCLUSIONS: Visilizumab had an acceptable safety profile at the 10-microg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid-refractory ulcerative colitis.

Hanauer S, Good LI, Goodman MW, Pizinger RJ, Strum WB, Lyss C, Haber G, Williams CN, Robinson M. · University of Chicago Medical Center, Illinois 60637, USA. · Am J Gastroenterol. · Pubmed #10925979 No free full text.

Abstract: OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission. METHODS: In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy). RESULTS: Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events. CONCLUSIONS: The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.

Yun L, Hanauer S. · Division of Gastroenterology, Department of Medicine, University of Chicago Hospitals, Chicago, IL 60637, USA. · Expert Rev Gastroenterol Hepatol. · Pubmed #19485806 No free full text.

Abstract: Infliximab was the first anti-TNF agent to be approved by the US FDA for the treatment of Crohn's disease (CD) in 1998. In the past 10 years, two other agents, adalimumab and certolizumab pegol, have also been approved for the treatment of CD. In the absence of head-to-head comparisons, the efficacy of these agents appear to be similar for the treatment of luminal CD. There are also prospective, randomized, controlled data to support the use of infliximab for the treatment of fistulizing CD and ulcerative colitis, and supportive post hoc data for the use of adalimumab and certolizumab pegol for the treatment of fistulizing CD. Practical matters, such as patient preference regarding the mode of administration, approval by third-party payers and residual patient cost, may actually play a larger role in choosing a particular anti-TNF agent, as efficacy and safety issues are similar for all three. Unfortunately, many patients do not respond, lose response or develop intolerance to anti-TNF treatment. Thus, new therapies are needed. Natalizumab, the first biologic that is not an anti-TNF agent, was FDA-approved in January 2008 for the treatment of CD patients who have failed conventional treatment, including anti-TNF therapy. As we continue to learn more about the pathogenesis of inflammatory bowel disease, novel targets for drug therapy are being developed.

Sands BE, Sandborn WJ, Feagan B, Löfberg R, Hibi T, Wang T, Gustofson LM, Wong CJ, Vandervoort MK, Hanauer S, Anonymous00103. · MGH Crohn's & Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Gastroenterology. · Pubmed #18602921 No free full text.

Abstract: BACKGROUND & AIMS: Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis. Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis. METHODS: We evaluated the efficacy of granulocyte/monocyte apheresis in a randomized, double-blind, sham-controlled trial in patients with active moderate-to-severe ulcerative colitis (Mayo score 6-11) in community-based and tertiary care centers. As intervention, we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System (JIMRO, Ltd, Takasaki, Japan) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study (N = 168) and in a smaller, companion study of identical design conducted in Europe and Japan (N = 47). RESULTS: In the pivotal study, clinical remission rates (Mayo score 0-2, with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination) were 17% and 11% for the granulocyte/monocyte apheresis (n = 112)- and sham-treatment groups, respectively (n = 56; P = .361). Clinical response (Mayo score reduction of >/=3 points from baseline) was observed in 44% and 39% of patients, respectively (P = .620). Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response, and changes in Mayo and quality-of-life scores. The companion study and pooled data from both studies also yielded similar results. CONCLUSIONS: In this study, granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis.

Kane S, Kisiel J, Shih L, Hanauer S. · University of Chicago, Chicago, Illinois, 60637, USA. · Am J Gastroenterol. · Pubmed #15307871 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel disease (IBD) activity during pregnancy is variable and factors influencing the course unknown. We studied the relationship between maternal-fetal HLA disparity and IBD course. METHODS: Women with IBD and childbirth were recruited and medical records were reviewed for five time periods. Twenty milliliters of blood was obtained from mother and child for genotyping. Each mother/child pair was assigned an HLA disparity status (+/-) for HLA A, B, C, DRB1, and DQ loci. Odds ratios were calculated comparing HLA disparity in women whose IBD improved versus those whose disease worsened or remained active. RESULTS: Fifty pregnancies in 38 women were studied. Forty-two of 50 pregnancies (84%) were disparate at the DRB1 locus; 34 (68%) were mismatched at the DQ locus. There was no difference in average disease score or overall activity score based on DRB1 or DQ disparity (p > 0.05 for all comparisons). There were 31 pregnancies disparate at both DRB1 and DQ loci; a significant difference was found in average disease scores and overall activity scores between women mismatched at both loci versus only one or neither locus (OR 8.4 [1.5-14, p = 0.01). Logistic regression identified prepartum disease activity and disparity at both DRB1 and DQ as significant predictors of overall disease activity during pregnancy. CONCLUSION: Improvement of IBD symptoms during pregnancy is associated with disparity in HLA class II antigens between mother and fetus. This suggests that the maternal immune response to paternal HLA antigens plays a role in pregnancy-induced remission. What is accepted and what this research adds are as follows: .The course of IBD during pregnancy is variable. .The factors involved with disease course are unknown. .The data presented here provides a scientific mechanism for disease course during pregnancy. .This is a novel work and it corroborates what has been seen in other autoimmune conditions.

Kane S, Huo D, Aikens J, Hanauer S. · Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. · Am J Med. · Pubmed #12543288 No free full text.

Abstract: PURPOSE: We conducted a prospective study to determine the effects of nonadherence with mesalamine among patients with quiescent ulcerative colitis. METHODS: We followed a cohort of 99 consecutive patients who had ulcerative colitis in remission for more than 6 months and who were taking maintenance mesalamine. Medication adherence rates were calculated based on pharmacy records and a validated formula. Nonadherence was defined as refilling less than 80% of prescribed medication. Patients were followed prospectively and evaluated either in clinic or via telephone at 6, 12, and 24 months. The primary outcome was clinical recurrence of ulcerative colitis. Proportional hazards models were used to adjust for confounders. RESULTS: At 6 months, 12 patients (12%) had clinical recurrence of disease symptoms, all of whom were nonadherent with medication. At 12 months, 19 of 86 patients had recurrent disease, 13 (68%) of whom were nonadherent. Patients who were not adherent with medication had more than a fivefold greater risk of recurrence than adherent patients (hazard ratio = 5.5; 95% confidence interval: 2.3 to 13; P < 0.001). CONCLUSION: Nonadherence with medication increases the risk of clinical relapse among patients with quiescent ulcerative colitis. Future research should be directed at behavioral interventions to improve adherence.