Conectar
In individuals at-risk of rheumatoid arthritis (RA), to investigate how joint tenderness and patient-reported joint pain (PRJP) relate to ultrasound abnormalities and assess whether these exploratory results could be used to assist future evaluation of symptom/signs-guided ultrasound scanning approaches in this population.
This is a cross-sectional analysis from a Leeds (UK) cohort of anti-cyclic citrullinated peptide (anti-CCP) positive individuals with new musculoskeletal complaints and no clinical arthritis. Assessments included physical examination, a mannequin where participants ticked joints that were painful and ultrasound scans of wrists, metacarpo-phalangeal joints 1–5 (MCPs1-5), proximal interphalangeal joints 1–5 (PIPs1-5), elbows, knees, ankles, metatarso-phalangeal joints 1–5 (MTPs1-5), finger flexor tendons (2-5) and extensor carpi ulnaris. Grey scale (GS), power Doppler (PD), tenosynovitis and erosions were assessed. A generalised estimating equations model was used to evaluate potential associations between tenderness/PRJP and ultrasound findings at the joint-level, adjusting for age and sex. Positive and negative predictive values for ultrasound changes were calculated.
323 participants were analysed. Joint tenderness was associated with ultrasound abnormalities, predominantly PD in wrists, MCPs, PIPs, elbows, knees and MTPs. GS and erosions were also associated with tenderness, but to a lesser degree. Association of PRJP with ultrasound abnormalities was more inconsistent and mostly for GS in the feet (all p≤0.05). Absence of symptoms and signs had a negative predictive value between 97% and 100% in all joints, except in wrists; which was slightly lower.
In anti-CCP positive individuals at risk of RA, tenderness, predominantly in the small joints, was associated with local inflammatory changes on ultrasound. The association of PRJP and ultrasound was limited. In the absence of tenderness, the presence of PD, tenosynovitis or erosions was uncommon. These findings may inform future studies evaluating symptom/sign-guided ultrasound assessment approaches in at-risk populations.
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.
An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.
This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.
No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.
CRD42025644244.
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