Adalimumab or infliximab as monotherapy, or in combination with an immunomodulator, in the treatment of Crohn's disease.

BACKGROUND: The comparative efficacy of adalimumab (ADA) and infliximab (IFX) in Crohn's disease, and the benefit of initial combotherapy with an immunomodulator, are debated. AIM: To assess the best anti-TNF treatment regimens in Crohn's disease. METHODS: We included 906 biologic-naïve Crohn's disease patients [median age, 31 years (24-41)] and performed a retrospective analysis of 1284 therapeutic exposures to ADA (n = 521) or IFX (n = 763) between 2006 and 2015. An immunomodulator was associated during the first 4-6 months (initial combotherapy) during 706 therapeutic exposures (55%). Median duration of anti-TNF therapy was 39 months (IQR 17-67). Primary outcomes were 6-month and 2-year response rates and drug survival. Logistic regression with propensity scoring and Cox proportional hazard analysis determined variables associated with outcomes. RESULTS: The response rates at 6 months and 2 years were 64% and 44% on ADA mono, 86% and 70% on ADA combo, 72% and 45% on IFX mono, and 84% and 68% on IFX combotherapy, respectively. Differences between ADA and IFX were not significant, whereas combotherapy was superior to monotherapy (P < 0.001). Drug survival was longer with combotherapy vs. monotherapy [adjusted hazard ratio 2.17 (1.72-2.70)] and not significantly different between ADA and IFX. During subsequent anti-TNF exposures, IFX combotherapy fared better than other groups regarding response rates, drug survival, disease activity, hospitalisations and abdominal surgery. CONCLUSION: In this retrospective analysis of a large tertiary centre cohort of Crohn's disease patients, ADA and IFX had similar efficacy as first line treatment, while initial combotherapy with an immunomodulator improved all outcome measures.

Management of acute sigmoid volvulus: short- and long-term results.

AIM: The best form of prophylactic management of a decompressed sigmoid volvulus (SV) is controversial especially in the elderly. We have studied our experience with this condition to assess the short- and long-term results of SV management. METHOD: All patients treated for SV in our department between 2003 and 2013 were retrospectively included. Emergency decompression was attempted in all patients in whom there was no sign of peritonitis. Planned surgical resection was the procedure of choice in young patients. Percutaneous endoscopic colopexy (PEC) was used in high surgical risk patients. RESULTS: There were 65 patients (45 males) of median age 71.5 (24-99) years. Non-surgical reduction was performed in 62 with a success rate of 95% (59/62). Recurrence after initial decompression was 67% at a median follow-up of 5 (1-14) years. A prophylactic surgical resection was performed with primary anastomosis in 33 patients. There were no deaths and the major morbidity rate was 6%. At a mean follow-up of 62 months, only 1 (3%) patient had had a recurrence (at 130 months). PEC was performed in six patients of median age 90 (84-99) years and with a median American Society of Anesthesiologists score of 4. Complications included local site infection (n = 2), pain (n = 1) and abdominal wall bleeding (n = 1). After a median follow-up of 2 (1-4) years, three patients died from medical causes and one recurrence occurred 13 months after removal of the PEC tube. CONCLUSION: Prophylactic treatment after initial decompression of SV results in a low rate of recurrence. Planned sigmoid resection is safe and effective. In frail elderly patients, PEC is satisfactory.

Impact of the diagnosis and treatment of cancer on the course of inflammatory bowel disease.

BACKGROUND: The effects of extra-intestinal cancer on the course of inflammatory bowel disease (IBD) are poorly understood. AIM: To evaluate the impact of cancer and its management on IBD outcomes. METHODS: A total 80 IBD patients (51 Crohn's disease, 29 ulcerative colitis; 33 men, median age at cancer diagnosis 48yrs) diagnosed with extra-intestinal cancer were selected from a prospective database. IBD activity and therapeutic requirements (assessed year-by-year) were compared before and after cancer diagnosis, with a control group of patients without cancer matched for gender, birth date, date of IBD diagnosis and IBD phenotype. RESULTS: Paired comparisons of the consecutive periods before and after cancer diagnosis did not show significant changes in median (IQR) percentages of years with active disease (27% [0-50] vs. 19% [0-53]), while the proportion of patient-years on any immunosuppressant remained stable (26% vs. 28%). Chemotherapy had no significant effect on IBD activity. Compared to controls, patients with cancer had a similar IBD activity and use of anti-TNF, but less use of immunomodulators (19% vs. 25%, p<0,001) and an increased rate of surgery (4% vs. 2.5%, p<0,05). Individual variations in IBD activity after cancer diagnosis were not significantly different in patients with cancer and their matched controls. CONCLUSION: Occurrence of extra-intestinal cancer impacts IBD therapeutic management, with a trend towards less use of immunomodulators and more surgery. In the long-term, cancer diagnoses and treatments do not modify IBD outcomes.

[Complications of celiac disease]. / Les complications de la maladie cœliaque.

Numerous complications can occur in celiac disease, nutritional (growth failure in children, malnutrition, vitamin deficiencies), hematologic (anaemia), bone disease (osteoporosis, fracture), gynaecologic (hypo fertility), cardiovascular (coronaropathy, venous thrombosis), neurological (peripheral neuropathy), hepatic (cytolysis, cirrhosis). Celiac disease is associated with an increased risk of autoimmune diseases (type 1 diabetes, thyroiditis), and cancer (upper digestive tract, hepatocellular carcinoma, lymphoma). The main digestive complications are microscopic colitis and refractory sprue, which are resistant to gluten-free diet. It can be associated with a monoclonal proliferation of intraepithelial lymphocytes (type 2 refractory sprue), which may be considered as a cryptic lymphoma and can lead to invasive T lymphoma, which occurs in one celiac patient in 1000. Gluten-free diet protects from the occurrence of most complications and correct the over-mortality related to these complications.

Incidence of benign upper respiratory tract infections, HSV and HPV cutaneous infections in inflammatory bowel disease patients treated with azathioprine.

BACKGROUND: There are few data on the incidence of benign infections (upper respiratory tract infections, herpes lesions and viral warts) during exposure to azathioprine. AIMS: To determine the incidence of benign infections in IBD out-patients receiving azathioprine (AZA+) and to look at the influence of leucocyte counts in the onset of these events. METHODS: A total of 230 patients were included in a prospective cohort and observed during 207 patient-years. Episodes of benign infections were collected and incidences of benign infections were compared between the AZA+ group and patients without AZA (AZA-). RESULTS: The incidence of upper respiratory tract infections in the cohort was 2.1 +/- 2.2 per observation-year. There was no difference between the AZA+ (n = 169) and AZA- (n = 61) groups (2.2 +/- 2.3 vs. 2.1 +/- 2.1, P = 0.77). The incidence of herpes flares was significantly increased in the AZA+ group compared to the AZA- group (1.0 +/- 2.6 vs. 0.2 +/- 0.8 per year, P = 0.04). Similarly, there were significantly more patients with appearance or worsening viral warts in the AZA+ group (17.2% (AZA+) vs. 3.3% (AZA-), P = 0.004). CONCLUSION: This study suggests that the incidence of herpes flares and the appearance or worsening of viral warts are increased in IBD patients receiving AZA.

Low counts of Faecalibacterium prausnitzii in colitis microbiota.

BACKGROUND: The intestinal microbiota is suspected to play a role in colitis and particularly in inflammatory bowel disease (IBD) pathogenesis. The aim was to compare the fecal microbiota composition of patients with colitis to that of healthy subjects (HS). METHODS: fecal samples from 22 active Crohn's disease (A-CD) patients, 10 CD patients in remission (R-CD), 13 active ulcerative colitis (A-UC) patients, 4 UC patients in remission (R-UC), 8 infectious colitis (IC) patients, and 27 HS were analyzed by quantitative real-time polymerase chain reaction (PCR) targeting the 16S rRNA gene. Bacterial counts were transformed to logarithms (Log(10) CFU) for statistical analysis. RESULTS: Bacteria of the phylum Firmicutes (Clostridium leptum and Clostridium coccoides groups) were less represented in A-IBD patients (9.7; P = 0.004) and IC (9.4; P = 0.02), compared to HS (10.8). Faecalibacterium prausnitzii species (a major representative of the C. leptum group) had lower counts in A-IBD and IC patients compared to HS (8.8 and 8.3 versus 10.4; P = 0.0004 and P = 0.003). The Firmicutes/Bacteroidetes ratio was lower in A-IBD (1.3; P = 0.0001) and IC patients (0.4; P = 0.002). Compared to HS, Bifidobacteria were less represented in A-IBD and IC (7.9 and 7.7 versus 9.2; P = 0.001 and P = 0.01). CONCLUSIONS: The fecal microbiota of patients with IBD differs from that of HS. The phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A-IBD patients as well as in IC patients. These bacteria could be crucial to gut homeostasis since lower counts of F. prausnitzii are consistently associated with a reduced protection of the gut mucosa.

Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery.

BACKGROUND/AIM: Immunosuppressants are now used much earlier in the course of Crohn's disease; however their effect on the natural history of the disease, especially on the need for surgery, is not known. The aim of this study was to assess the evolution of the need for surgery in Crohn's disease during the last 25 years. PATIENTS AND METHODS: The medical charts of 2573 patients were reviewed retrospectively. The use of immunosuppressants (azathioprine or methotrexate), the need for intestinal resection, and the occurrence of intestinal complications were assessed using Kaplan-Meier analysis in five consecutive cohorts of patients defined by the date of diagnosis of Crohn's disease (1978-82; 1983-87; 1988-92; 1993-97; 1998-2002). RESULTS: In 565 patients seen in the authors' unit within the first three months after diagnosis, characteristics of Crohn's disease at diagnosis did not differ from one cohort to another. The five year cumulative probability to receive immunosuppressants increased from 0 in the 1978-82 cohort to 0.13, 0.25, 0.25, and 0.56 in the 1983-87, 1988-92, 1993-97, and 1998-2002 cohorts, respectively (p<0.001). Concomitantly, the cumulative risk of intestinal resection remained unchanged (from 0.35 to 0.34 at five years; p=0.81). The cumulative risk of developing a stricturing or a penetrating intestinal complication remained also unchanged. Similar results were obtained in the 2008 patients seen during the same period who were referred to us more than three months after diagnosis. CONCLUSION: Although immunosuppressants have been used more frequently over the last 25 years, there was no significant decrease of the need for surgery, or of intestinal complications of Crohn's disease.