Exploring TNFi drug-levels and anti-drug antibodies during tapering among patients with inflammatory arthritis: secondary analyses from the randomised BIODOPT trial

To evaluate tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥ 12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb. In total, 129 patients were randomised to tapering (n = 88) or control (n = 41). Between baseline and month 18, a significant shift in TNFi drug-levels were observed in the tapering group resulting in fewer patients with high drug-levels (change: − 14% [95% CI − 27 to − 1%]) and more with low drug-levels (change: 18% [95% CI 5–31%]). Disease activity was equivalent between groups at 18 months, mean difference: RA − 0.06 (95% CI − 0.44 to 0.33), PsA 0.03 (95% CI − 0.36 to 0.42), and axSpA 0.16 (− 0.17 to 0.49), equivalence margins ± 0.5 disease activity points. ADAb were detected in eight patients, all from the tapering group. TNFi drug-level category or ADAb were not predictive for achieving successful tapering at 18 months. TNFi drug-levels decreased during tapering which indicate adherence to the tapering algorithm. Despite the difference in TNFi drug-levels at 18 months, disease activity remained equivalent, and only few tapering patients had detectable ADAb. These data do not support using TNFi drug-level and/or ADAb to guide the tapering decision but future research with larger trials is needed. Trial registration: EudraCT: 2017-001970-41, December 21, 2017

Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial.

OBJECTIVE: To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day. DESIGN: Randomised controlled trial. SETTING: Copenhagen, Denmark. SUBJECTS: 42 alcoholic patients without liver disease admitted for elective colorectal surgery. INTERVENTIONS: Withdrawal from alcohol consumption for 1 month before operation (disulfiram controlled) compared with continuous drinking. MAIN OUTCOME MEASURES: Postoperative complications requiring treatment within the first month after surgery. Perioperative immunosuppression measured by delayed type hypersensitivity; myocardial ischaemia and arrhythmias measured by Holter tape recording; episodes of hypoxaemia measured by pulse oximetry. Response to stress during the operation were assessed by heart rate, blood pressure, serum concentration of cortisol, and plasma concentrations of glucose, interleukin 6, and catecholamines. RESULTS: The intervention group developed significantly fewer postoperative complications than the continuous drinkers (31% v 74%, P=0.02). Delayed type hypersensitivity responses were better in the intervention group before (37 mm(2) v 12 mm(2), P=0.04), but not after surgery (3 mm(2) v 3 mm(2)). Development of postoperative myocardial ischaemia (23% v 85%) and arrhythmias (33% v 86%) on the second postoperative day as well as nightly hypoxaemic episodes (4 v 18 on the second postoperative night) occurred significantly less often in the intervention group. Surgical stress responses were lower in the intervention group (P⩽0.05). CONCLUSIONS: One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers. The mechanism is probably reduced preclinical organ dysfunction and reduction of the exaggerated response to surgical stress