Efficacy and safety of adalimumab 80 mg weekly in luminal Crohn's disease.

BACKGROUND: In case of a loss of response to adalimumab, some patients with Crohn's disease may derive benefit from increasing the dosing frequency to 40 mg weekly. Efficacy and safety of adalimumab 80 mg weekly remain unknown. METHODS: From February 2011 to September 2012, all adults who had active Crohn's disease, defined at least by Crohn's disease activity index >150 and 1 objective sign of inflammation, and required an adalimumab dose escalation to 80 mg weekly were enrolled in a prospective multicenter cohort study. Crohn's disease activity index and C-reactive protein levels were recorded during the first 14 weeks following adalimumab optimization and at 6 months. All adverse events were recorded. RESULTS: Forty-two patients were included. The median age was 33 years, and the median disease duration was 8.6 years. Adalimumab was associated with steroids in 28% of cases and with immunomodulators in 10% of patients. Within the 14 weeks after adalimumab optimization, 14 patients (33.3%) achieved clinical remission (Crohn's disease activity index <150), and 23 patients (54.8%) had a clinical response. Clinical improvement was associated with a drop in the C-reactive protein level from 18 to 5 mg/L (P = 0.0008). After a median follow-up of 14.5 months, 5 patients underwent major abdominal surgery. Adverse events were reported in 13 patients (31%). CONCLUSIONS: Adalimumab 80 mg weekly seems to be well-tolerated and may be effective in inducing clinical remission in patients with luminal Crohn's disease who failed to respond to 40 mg weekly or 80 mg every other week.

Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer.

OBJECTIVE: To explore the risk of new or recurrent cancer among patients with IBD and previous cancer, exposed or not to immunosuppressants. DESIGN: Among the 17 047 patients of the CESAME prospective observational cohort who were enrolled from May 2004 to June 2005, and followed-up until December 2007, we identified 405 patients with cancer diagnosed previous to study entry. We calculated the rates of incident cancer in patients with or without previous cancer, and we assessed by survival analysis and nested case-control study the impact of immunosuppressants on the risk of incident new or recurrent cancer in patients with previous cancer. RESULTS: The rate of incident cancer was 21.1/1000 patient-years (PY) and 6.1/1000 PY in patients with and without previous cancer, respectively. The multivariate-adjusted HR of incident cancer between patients with and without previous cancer was 1.9 (95% CI 1.2 to 3.0, p=0.003). Among patients with previous cancer, the rates of new and recurrent cancers were, respectively, 13.2/1000 PY and 6.0/1000 PY in the 312 patients who were not taking immunosuppressant at the time of study entry, and 23.1/1000 PY and 3.9/1000 PY in the 93 patients treated with immunosuppressants at study entry. There was no significant association between the exposure to immunosuppressants and the risk of new or recurrent cancer. CONCLUSIONS: Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk.

Tolerability of one hour 10mg/kg infliximab infusions in inflammatory bowel diseases: a prospective multicenter cohort study.

BACKGROUND AND AIM: In patients with inflammatory bowel disease (IBD) tolerating 2-h infusions of 5mg/kg infliximab scheduled maintenance therapy, the infusion time can be shortened to 1-h with good tolerability. A retrospective study with small sample size demonstrated the feasibility of 1-hour infusion time for 10mg/kg infliximab in IBD patients. METHODS: Between November 2011 and July 2012, 63 patients received 1-hour 10mg/kg infliximab infusions under standard operating procedures and were enrolled in a prospective observational study. Intravenous steroid premedication was given to all patients. RESULTS: Sixty-three IBD patients on infliximab maintenance therapy (43 Crohn's disease, 34 males) received 1-hour 10mg/kg infusions during the study period. A total of 182 infliximab infusions were administered. Seventeen (26%) patients were receiving concomitant immunomodulators. Two patients experienced (2/182, 1%) severe acute infusion reactions consisting on a cutaneous lupus and one severe anaphylactic reaction. We also observed one (1/182, 0.5%) severe delayed reaction after the first 1-hour infliximab infusion consisting on acne generalis. All 3 reactions led to infliximab discontinuation. No mild acute reactions and 6 mild delayed reactions (6/182, 3%) occurred. CONCLUSIONS: In patients with IBD receiving infliximab scheduled maintenance therapy, 1-hour infusion time for 10mg/kg infliximab seems to be well tolerated. This option might be considered in clinical practice in order to decrease the extra-burden of infliximab infusions in this patient population.

Tolerability of one hour 10 mg/kg infliximab infusions in patients with inflammatory bowel disease.

BACKGROUND AND AIM: In patients with inflammatory bowel disease (IBD) tolerating 2-h infusions of 5mg/kg infliximab scheduled maintenance therapy, the infusion time can be shortened to 1-h with good tolerability. The tolerability of one 1-hour 10 mg/kg infliximab infusion in patients with IBD is unknown. METHODS: Between August and September 2011, 8 patients received one 1-hour 10mg/kg infliximab infusion. All patients were treated in our infusion unit under standard operating procedures. Intravenous steroid premedication was given to all patients. These 8 patients were compared to 26 IBD patients who received one 1-hour 5mg/kg infliximab infusion during the same study period at Nancy University Hospital. The charts of these 34 patients were reviewed to assess tolerability of 1-hour infliximab infusions. RESULTS: A total of 34 patients with IBD on infliximab maintenance therapy (82.4% Crohn's disease, 17.6% ulcerative colitis; 22 females) received one 1-hour 5 or 10mg/kg infusion. Four patients were receiving concomitant immunomodulators. No severe infusions reactions were reported in the 34 IBD patients. Two mild acute reactions (7.7%) and two delayed reactions (7.7%) occurred in the 5mg/kg infliximab group. We did not observe any acute or delayed infliximab reactions in the 10mg/kg patients group. CONCLUSIONS: In patients with inflammatory bowel disease receiving infliximab scheduled maintenance therapy, 1-hour infusion time for 10mg/kg infliximab appears to be well tolerated. Large prospective studies are needed to confirm our findings.