Biological treatment interruption in inflammatory bowel disease: Motivation and predictive factors.

BACKGROUND: Loss-of-response and adverse events (AE) to biologics have been linked to HLA-DQA1*05 allele. However, the clinical factors or biologic used may influence treatment duration. Our objective was to evaluate the influence of clinical and therapeutic factors, along with HLA, in biological treatment discontinuation. METHODS: A retrospective study of consecutive IBD patients treated with biologics between 2007 and 2011 was performed. Main outcome was treatment discontinuation due to primary non-response (PNR), secondary loss of response (SLR) or AE. HLA-DQA1 genotyping was done in all patients. Regression analyses were used to assess risk factors of treatment discontinuation. RESULTS: One hundred fifty patients (61% male) with 312 biologic treatments were included. 147 (47%) were discontinued with a cumulative probability of 30%, 41% and 56% at 1, 2 and 5 years. The use of infliximab (p=0.006) and articular manifestations (p<0.05) were associated with treatment discontinuation. Considering cause of withdrawal, Ulcerative Colitis (UC) had a higher proportion of PNR (HR=4.99; 95% CI=1.71-14.63; p=0.003), SLR was higher if biologics had been indicated due to disease flare (HR=2.32; 95% CI=1.05-5.09; p=0.037) while AE were greater with infliximab (HR=2.46; 95% CI=1.48-4.08; p<0.001) or spondylitis (HR=2.46; 95% CI=1.78-6.89; p<0.001). According to the biological drug, HLA-DQA1*05 with adalimumab showed more SLR in cases with Crohn's disease (HR=3.49; 95% CI=1.39-8,78; p=0.008) or without concomitant immunomodulator (HR=2.8; 95% CI=1.1-6.93; p=0.026). CONCLUSIONS: HLA-DQ A1*05 was relevant in SLR of IBD patients treated with adalimumab without immunosupression. In patients treated with other biologics, clinical factors were more important for treatment interruption, mainly extensive UC or extraintestinal manifestations and having indicated the biologic for flare.

Amyloidosis in Inflammatory Bowel Disease: A Systematic Review of Epidemiology, Clinical Features, and Treatment.

BACKGROUND AND AIMS: Amyloidosis is a rare complication of inflammatory bowel disease [IBD]; its low prevalence has hindered both descriptive and therapeutic studies. The aim of this study was to estimate the prevalence of amyloidosis in IBD and the risk factors associated with this complication. METHODS: This paper presents an observational study, followed by a systematic review of the epidemiological and clinical characteristics of the disease and a review of the diagnostic and therapeutic options. RESULTS: The prevalence of amyloidosis among IBD patients is 0.53% (95% confidence interval [CI]: 0.32-0.75), although epidemiological data suggest that it may be under-diagnosed. The phenotype most frequently associated with amyloidosis is males with aggressive and extensive Crohn's disease, fistulising behaviour, perianal disease, and extra-intestinal complications, with the development of proteinuria and renal failure. CONCLUSIONS: Identifying risk factors of amyloidosis in IBD patients and screening for proteinuric renal dysfunction are useful to improve diagnostic accuracy. Referral of biopsies to a tertiary centre should also be considered, to improve diagnostic accuracy. Although there is no reliable evidence on the effectiveness of treatment, it seems reasonable to treat the underlying disease with potent immunosuppression to minimise inflammatory activity, thereby switching off amyloidogenesis.