Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitor-induced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids: REACT trial protocol

Sep 23, 2026

Pragmatic REACT is a prospective, multicentre, open-label, superiority, two-arm randomised controlled trial addressing immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). The study compares current standard therapy with initial prednisolone against up-front adalimumab without glucocorticoids to test faster and more effective symptom control, reduced glucocorticoid exposure, and improved remission. Primary analysis evaluates glucocorticoid-free arthritis remission at 24 weeks, defined by no systemic or intra-articular glucocorticoid use (except adrenal insufficiency) and absence of synovitis.

LanguageEnglish

CategoryResearch & Report

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Pages10

Reading Time25 min

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Abstract

Strengths and Limitations of This Study

Methods and Analysis

Ethics and Dissemination

Introduction

Open access Protocol Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitor-induced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids: REACT trial protocol Benjamin A Fisher ,1,2,3 Anna Rowe,2,3 Chris Hodson,4 Manpreet Wilkhu,2 Emily Williams,2 Elliot Turner,2 Andrew Allard,5 Tim Blake,6 Michele Bombardieri,7 Andrew P Cope,8 Shirish Dubey,9,10 Kulveer Mankia,11,12 Tamir Malley,13 Owen Moore,14 Miranda Payne,15 Ruth Plummer,16,17 Michael Tilby,18 Tania Tillett,19 Ernest Wong,20 Yin Wu,21,22 Andrew Filer,1,3 Arthur Pratt,17,23,24 Lalit Pallan,25 Victoria Homer2,3 To cite: Fisher BA, Rowe A, Hodson C, et al. Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitorinduced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids: REACT trial protocol. BMJ Open 2026;16:e116847 . doi:10 . 1136/ bmjopen-2026-116847 ► Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[bmjopen-2026-116847](bmjopen-2026-116847)) . CH since deceased. Received 14 January 2026 Accepted 12 February 2026 © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. For numbered affiliations see end of article. Correspondence to Dr Benjamin A Fisher; [b.fisher@bham.ac.uk](b.fisher@bham.ac.uk) ABSTRACT Introduction Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) . ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors. A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with nonspecific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes. Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front antiTNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ REACT tests the most widely used anti-TNF agent in the UK, adalimumab, which has the convenience of subcutaneous administration. ⇒ Adalimumab is being used without glucocorticoids, avoiding unnecessary over-immunosuppression. ⇒ The lack of placebo reduces burden, complexity and cost of the trial. ⇒ REACT has been co-developed with patient partners who co-designed the patient-centred ranked composite outcome that will be used as an exploratory outcome. ⇒ REACT does not use loading doses of adalimumab, which have been shown to

FAQs

What question does the REACT trial protocol address?

Whether initiating anti-TNF therapy with adalimumab earlier in ICI-IA management can more effectively and quickly control symptoms while reducing glucocorticoid exposure.

How is treatment allocation designed in the REACT trial?

Participants receive either standard of care with initial prednisolone (Arm A) or adalimumab without glucocorticoids (Arm B) in a two-arm, randomised controlled design.

What is the primary outcome of the trial at 24 weeks?

Glucocorticoid-free arthritis remission rate at 24 weeks, defined by no systemic or intra-articular glucocorticoid use within 4 weeks before assessment (except adrenal insufficiency) and absence of synovitis on clinical examination.

Sep 23, 2026

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