Ulcerative Colitis: Lemann M

Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. · Department of Gastroenterology, Hôpital Saint-Louis, Paris, France. · Aliment Pharmacol Ther. · Pubmed #12869077 links to  free full text

Abstract: BACKGROUND: The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting. METHODS: The records of 30 patients treated with infliximab for ulcerative colitis (n=19) or indeterminate colitis (n=11) were reviewed. Infliximab was given because of steroid resistance (n=18), dependence (n=5) or intolerance (n=7); five patients had failed on cyclosporin; 19 patients had a severe flare-up. RESULTS: Median duration of follow-up was 10 months. In 28 patients with active disease, the response rate was 75% at day 7, with 43% having a complete remission, and 50% at month 1, with 32% having a complete remission. Among the 22 responders, the probability of relapse was 73% at month 6. The probability of complete remission without steroids, taking into account the re-treatment for relapse (n=11), was 57% (95% confidence interval (CI): 45% to 69%) at month 6. The probability of colectomy was 33% (95% CI: 23% to 43%) at month 12. In indeterminate colitis, response rate was only 50% at day 7 and 30% at month 1. Concomitant use of antimetabolite agents was associated with better results. CONCLUSIONS: Infliximab was able to induce a rapid response in some patients with UC or indeterminate colitis refractory to conventional treatment. Long-term results were less favourable, with frequent relapses, and about one-third of the patients required a colectomy.

Thiébaut R, Kotti S, Jung C, Merlin F, Colombel JF, Lemann M, Almer S, Tysk C, O'Morain M, Gassull M, Binder V, Finkel Y, Pascoe L, Hugot JP. · INSERM, U843, Hôpital Robert Debré, Université Paris Diderot, Paris, France. · Am J Gastroenterol. · Pubmed #19174806 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.

Branche J, Cortot A, Bourreille A, Coffin B, de Vos M, de Saussure P, Seksik P, Marteau P, Lemann M, Colombel JF. · Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Huriez, CHU Lille, Lille, France. · Inflamm Bowel Dis. · Pubmed #19137604 No free full text.

Abstract: BACKGROUND: Cyclosporine is considered a safe and effective treatment of severe steroid-refractory ulcerative colitis (UC). However, few data are available concerning its safety profile in pregnant women. We report here the experience of 5 GETAID centers. METHODS: In a retrospective study data on patients with severe UC treated with cyclosporine during pregnancy were extracted from medical records of consecutive patients treated between 2001 and 2007. RESULTS: Eight patients (median age 30.5 years old) were identified. At the time of flare-up the median duration of pregnancy was 11.5 weeks of gestation (range 4-25). Seven patients had pancolitis. All patients had more than 3 commonly used clinical and biological severity criteria. Three patients had severe endoscopic lesions and 5 patients had not. All patients received intravenous corticosteroids for at least 7 days before introduction of cyclosporine. Two patients received azathioprine during treatment with cyclosporine. No severe infections or other complications due to treatment were observed. Treatment was effective in 7/8 patients. One patient received infliximab due to cyclosporine therapy failure with a good outcome. No colectomy was performed during pregnancy. Seven pregnancies were conducted to term, but 1 in utero death occurred due to maternal absence of S-protein. Two newborns were premature, including 1 case of hypotrophy. No malformations were observed. CONCLUSIONS: In our experience, treatment with cyclosporine for steroid-refractory UC during pregnancy can be considered safe and effective.

Cacheux W, Seksik P, Lemann M, Marteau P, Nion-Larmurier I, Afchain P, Daniel F, Beaugerie L, Cosnes J. · Department of Gastroenterology, Assistance Publique des Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital, Paris, France. · Am J Gastroenterol. · Pubmed #18047542 No free full text.

Abstract: OBJECTIVES: Cyclosporine is an effective rescue therapy in steroid-refractory ulcerative colitis (UC) and may avoid immediate colectomy. However, the individual's response to cyclosporine is poorly predictable. The aim of this study was to identify predictive factors of the response to cyclosporine in steroid-refractory UC. METHODS: One hundred thirty-five patients with steroid-refractory UC, admitted consecutively between 1992 and 2004, were included. Data were collected on the first day of the cyclosporine therapy. Colonoscopy was performed within 2 days preceding or following the cyclosporine treatment in 118 patients for assessing the presence of severe endoscopic lesions. RESULTS: The actuarial rate of colectomy was 0.45 at 6 months. Cox analysis in the whole population selected three predictive criteria of colectomy: body temperature >37.5 degrees C (adjusted hazard ratio = 1.94, 95% confidence interval 1.51-2.49), heart rate >90 bpm (1.86, 1.45-2.38), and C-reactive protein (CRP) >45 mg/L (1.70, 1.34-2.16). In the 118 patients who underwent colonoscopy, the presence of severe endoscopic lesions was an independent predictive factor of colectomy (2.38, 1.80-3.14). Colonoscopy was decisive and changed the therapeutic decision in patients with one or two criteria: 71% of the patients with severe endoscopic lesions were colectomized versus 17% of the patients without severe endoscopic lesions (P < 0.001). Finally, the clinical, biological, and endoscopic criteria allowed the classification of the patients into two different groups (80%vs 20% colectomy at 6 months). CONCLUSION: In patients with steroid-refractory UC, the combination of simple criteria is useful to predict the response to cyclosporine. Colonoscopy is crucial in patients with intermediate clinical and biological severity.

Lemann M, Beaugerie L, Bouhnik Y, Flourié B, Reimund JM, Seksik P, Marteau P. · Service de gastroentérologie, Hôpital Saint Louis, 75010 Paris. · Gastroenterol Clin Biol. · Pubmed #15672574 No free full text.

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