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 non-specific 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 anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.

REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).

The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.

The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

ISRCTN18217497.

Cutaneous vascular anomalies and scars can cause significant physical and psychosocial difficulties for children, but can be ameliorated with pulsed dye laser (PDL) and neodymium-doped yttrium aluminium garnet (Nd:YAG) laser treatment. Given that multiple rounds of treatment are often required, and that the procedures are painful, achieving adequate analgesia is imperative in this setting. Paediatric procedural pain management guidelines suggest that multimodal non-pharmacological and pharmacological analgesia should be used for such procedures; however, the place of topical anaesthetic (TA) within this paradigm has not been adequately studied.

This feasibility and pilot trial will investigate the feasibility of performing a randomised, placebo-controlled trial assessing pain intensity in children receiving TA in conjunction with other multimodal analgesic methods for laser procedures. The primary objective of the trial will be to assess feasibility, and secondary objectives will be to assess pain intensity, acceptability of trial procedures to participating families and their clinical team, to assess the laser treatment response, and obtain data necessary for full-scale trial sample size calculations.

The trial will include 50 children aged 0–18 years old who are undergoing awake PDL and/or Nd:YAG laser treatment for scars or vascular anomalies. Patients will be randomised in a 1:1 ratio to receive either TA cream (lidocaine 2.5%/prilocaine 2.5% (Numit 5% cream, Ego Pharmaceuticals, Braeside, VIC, Australia)) or a placebo, along with our unit’s standard multimodal analgesic agents for laser treatment (including paracetamol, ibuprofen or oxycodone and intraprocedural sucrose solution or intranasal fentanyl). Investigators, participants and their caregivers, and clinicians will be blinded to participant allocation.

The primary outcome of the trial will be trial feasibility based on pre-specified criteria. The secondary outcome of pain intensity will be assessed by observer, caregiver and self-reported measures, and the secondary outcome of trial method acceptability with a Theoretical Framework of Acceptability questionnaire. The assessment of laser treatment response will be assessed with lesion-specific evaluation tools. Feasibility and acceptability data will be summarised using descriptive statistics. The association between treatment groups and pain scores, treatment groups and laser treatment response will be investigated using a univariable linear regression model, with the effect estimate reported as mean difference and 95% CI.

This trial has undergone ethical review and has been granted approval by the Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (ref HREC/23/QCHQ/91002) and the Griffith University Human Research Ethics Committee (ref 2023/308). The protocol has been prospectively registered in the Australian and New Zealand Clinical Trials Registry (ACTRN12623000494639). Results of this trial may be presented at scientific meetings and will be published in a peer-reviewed journal. Participating families that have indicated an interest in trial results will receive a plain-language summary of the trial results by email.

ACTRN12623000494639.