ABSTRACT
BACKGROUND: The efficacy of adalimumab in maintaining remission in Crohn's disease patients may wane over time, leading to secondary loss of response that is often managed with dose escalation. However, the response to adalimumab dose escalation and long-term outcomes after escalation have not been well evaluated. AIMS: To characterise the short- and long-term clinical responses to adalimumab dose escalation for secondary loss of response. METHODS: A retrospective cohort study evaluating Crohn's disease out-patients requiring adalimumab dose escalation for secondary loss of response from 2003 to 2013 was conducted. The primary outcome was the proportion of patients achieving symptomatic clinical response to dose escalation and subsequent development of tertiary loss of response. Duration of regained response was assessed by Kaplan-Meier analysis. RESULTS: Ninety-two CD patients met inclusion criteria with mean duration of follow-up of 170.2 weeks (±129.6 weeks). Disease distribution was predominantly ileal (37/92, 40.2%) or ileocolonic (43/92, 46.7%), with equal distribution of inflammatory (34.8%), stricturing (27.2%), and penetrating (38.0%) disease phenotypes. At 24 weeks post-dose escalation, 74/92 (80.4%) patients had symptomatic clinical response. Among responders, median duration of sustained response was 69.2 weeks (IQR 29.4-107.1) but 42/74 (56.8%) responders experienced subsequent tertiary loss of response at a median time of 47.9 weeks (IQR 24.7-80.3). C-reactive protein >10.0 mg/L at the time of dose escalation predicted tertiary loss of response in univariate analysis (OR 3.32, 95% CI: 1.18-9.37). CONCLUSIONS: In patients with Crohn's disease, adalimumab dose escalation is effective for recapturing symptomatic response after secondary loss of response, but more than half will eventually experience a tertiary loss of response.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Adalimumab , Adult , Antibodies, Monoclonal/administration & dosage , Cohort Studies , Disease Management , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment Failure , Treatment OutcomeABSTRACT
BACKGROUND: The Epstein-Barr Virus (EBV) is truly prolific, with a prevalence of more than 90% in the adult human population. There are, however, little data available on the prevalence of EBV among patients with Inflammatory Bowel Disease (IBD), a population that is frequently immunosuppressed and thus at risk for severe, often fatal, primary infection. AIM: To identify the prevalence of EBV in a population of patients with IBD and to compare it with that of the general population. METHODS: A database of 2500 IBD patients previously followed at the University of Alberta IBD Centre was queried; 60 of these patients were randomly chosen to participate. A total of 220 patients attending the IBD Centre for clinical appointment were also prospectively asked to participate. Participants completed serological testing for VCA-IgM, VCA-IgG and EBNA-IgG, to determine prior EBV exposure. RESULTS: A total of 263 patients underwent testing. Results for EBV seroprevalence of specific age groups were as follows: 18-20 years (n = 17), 29% seronegative; 21-25 years (n = 31), 29% seronegative; 26-30 years (n = 35), 31-35 years (n = 18) and 36-40 years (n = 25), 100% seropositive. Finally, 3% of those older than 40 (n = 117) were seronegative. EBV seroprevalence was similar for Crohn's disease and ulcerative colitis. Azathioprine was associated with seropositivity (P = 0.048). CONCLUSION: The prevalence of EBV seronegativity in the IBD population aged 18-25 years was similar to that described in the general population, and above age 25 years, seropositivity approached 100%.
