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Background: Autoimmune hepatitis requires long-term therapy, and systemic corticosteroids are the backbone of therapeutic management. Prolonged use of corticosteroids may lead to adverse events but data from long-term studies are mainly derived from studies in rheumatic diseases., Aim: To assess cataract, diabetes and fractures in relation to corticosteroid doses in the long-term maintenance treatment of patients with autoimmune hepatitis., Methods: We retrospectively collected data on 476 patients (77% women) with an established diagnosis of autoimmune hepatitis. Binary logistic regression with a generalised estimating equation was used to analyse the association between current corticosteroid use and the incidence of cataract, diabetes and fractures with onset after autoimmune hepatitis diagnosis. We corrected for sex, age, cirrhosis at diagnosis and predniso(lo)ne use in the prior 3 years to account for possible ongoing effects., Results: A total of 6634 years, with a median of 13 (range 1-40) per patient were recorded. The median age at diagnosis was 44 years (range 2-88). Adverse events were documented in 120 (25%) patients. Low-dose predniso(lo)ne (0.1-5.0 mg/d) increased the odds of fractures whereas higher doses (>5.0 mg/d) increased the odds of cataracts and diabetes. Budesonide increased the odds of cataract and fractures; this effect was independent of predniso(lo)ne use in the prior 1, 2 or 3 years., Conclusions: Even low doses of corticosteroids frequently lead to substantial adverse events refuting the assumption that adverse events are prevented by administering low doses., (© 2019 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Tioguanine (or thioguanine) is an alternative drug for IBD patients who fail prior conventional immunomodulating therapy., Aim: To report effectiveness, safety and therapeutic drug monitoring in a cohort of patients with prolonged tioguanine maintenance therapy., Methods: In this nationwide, multicentre study, medical records of tioguanine- using IBD patients were retrospectively reviewed. Response to therapy was defined as clinical effectiveness without (re)initiation of corticosteroids, concurrent biological therapy or surgical intervention. All adverse events that occurred during the follow-up were listed and graded according to the common terminology criteria (CTC)., Results: Two hundred and seventy-four patients (female 63%, Crohn's disease in 68%) were included with median treatment duration of 51 months, 1567 patient-years of follow-up and median 20 mg/d tioguanine dosage. Tioguanine was tolerated in 79%, clinical effectiveness at 6 months was documented in 66% and sustained clinical effectiveness during 12 months in 51% of patients. Forty-one per cent of patients developed adverse events: 5% were graded as severe. Adverse events comprised infection requiring hospitalisation in three and skin cancer in eight patients (two melanomas). Asymptomatic nodular regenerative hyperplasia of the liver occurred in two out of 52 patients with liver biopsies (3.8%) and portal hypertension in three whereof one potentially associated with tioguanine (0.4%). Clinical effectiveness was correlated with 6-thioguanine nucleotide threshold concentrations >682 pmol/8×10 8 RBC (P < 0.05)., Conclusions: Long-term tioguanine therapy for at least 12 months was effective in 51% and well tolerated as a maintenance treatment for IBD in about 70% of patients. Adverse events were common, but mainly mild or moderate. 6-Thioguanine nucleotide threshold concentration ≥ 700 pmol/8×10 8 RBC is proposed as target level with higher odds for clinical effectiveness., (© 2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.)

Background: Off-label prescribing is encountered across various fields of medicine and creates alternative treatment options, but is associated with unknown safety risks. The use of off-label drugs for the treatment of patients with inflammatory bowel diseases (IBD) has not been characterised before., Aim: To assess the proportion and characteristics of off-label prescribing for IBD in tertiary care centres in the Netherlands., Methods: A prospective database of IBD patients from all Dutch university hospitals was used to collect data on drug prescriptions for IBD and demographics. Drugs were classified as off-label if they were unlicensed for Crohn's disease and/or ulcerative colitis by the Medicines Evaluation Board. Uni- and multivariable analyses were used to identify patient-specific characteristics predictive of increased off-label use., Results: For the induction and/or maintenance treatment of 4583 IBD patients, 12 651 historical and current drug records were available in the database. Of these, 2374 (19%) were considered off-label prescriptions. Out of 4583 IBD patients, 1477 (32%) were exposed to off-label drugs. Commonly prescribed off-label IBD drugs were mercaptopurine (18%), beclomethasone (12%), thioguanine (4%) and allopurinol (3%). Non-thiopurine/methotrexate off-label drugs were prescribed in 243 patients (6%), including biological agents or tofacitinib in 47 IBD patients (1%). Off-label prescriptions were more common in ulcerative colitis than Crohn's disease (37% vs 29%, P < 0.001). Smokers and patients that received ≥5 drug types during their disease course were more likely to be exposed to off-label drugs (smoking 33% vs 27% and multiple drug use 66% vs 22%, both P < 0.001)., Conclusion: About one-fifth of prescriptions for IBD were off-label and one-third of IBD patients, especially ulcerative colitis patients, were exposed to off-label drugs., (© 2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.)