Adalimumab Vs Placebo As Add-on to Standard Therapy for Autoimmune Uveitis: Tolerability, Effectiveness and Cost-effectiveness-a Protocol for a Randomised Controlled Trial (ASTUTE Trial)

Overview

Journal BMJ Open

Specialty General Medicine

Date 2024 Jan 24

PMID 38267244

Authors

Mae Hazell

Barnaby Reeves

Chris A Rogers

Katie Pike

Lucy Culliford

Sarah Baos

Mandy P Y Lui

Nicholas A V Beare

Carlos Pavesio

Alastair K Denniston

Sarah Wordsworth

Pearse A Keane

Robert Wilson

Annie Folkard

Tunde Peto

Srilakshmi M Sharma

Andrew Dick

Affiliations

Soon will be listed here.

Abstract

Introduction: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care.

Methods And Analysis: The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted.

Ethics And Dissemination: The trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available.

Trial Registration: ISRCTN31474800. Registered 14 April 2020.

Citing Articles

Evaluating patient-reported outcome measures (PROMs) for clinical trials and clinical practice in adult patients with uveitis or scleritis: a systematic review.

ODonovan C, Panthagani J, Aiyegbusi O, Liu X, Bayliss S, Calvert M J Ophthalmic Inflamm Infect. 2022; 12(1):29.

PMID: 36063293 PMC: 9443634. DOI: 10.1186/s12348-022-00304-3.

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