In patients with systemic sclerosis, interstitial lung disease (ILD) is the leading cause of mortality. Early detection of progressive ILD associated with systemic sclerosis is warranted for timely adjustment of management strategies and improved prognosis. We aimed to investigate the validity of home spirometry to detect a decline in pulmonary function in patients with systemic sclerosis-associated ILD.

Inflammation is an important risk factor, a potential therapeutic target for cognitive decline and dementia, and an inherent feature of autoimmune and immune-mediated rheumatic diseases. The risk of cognitive impairment and dementia is increased in individuals with immune-mediated rheumatic diseases, particularly in those with cardiovascular risk factors and cardiovascular disease. Immunomodulatory medications have been associated with a reduced risk of dementia, but whether this effect is mediated through their anti-inflammatory immunomodulating properties or other mechanisms, such as cardiovascular risk reduction, is unclear. A better understanding of the role of chronic inflammation as a modifiable risk factor for cognitive performance in rheumatic diseases will help inform opportunities for the management of cognitive impairment in people with rheumatic diseases and other chronic inflammatory diseases. In this Series paper, we discuss the epidemiology, risk factors, and current evidence on the role of immunomodulatory medications in cognitive impairment and dementia in people with rheumatic diseases.

Frailty represents a dynamic multisystem state of reduced physiological reserve that increases vulnerability to adverse health outcomes. Frailty occurs prematurely in adults with immune-mediated rheumatic diseases and is emerging as an important risk factor for adverse outcomes in these conditions. In this Series paper, we present a conceptual overview of frailty and its prevalence among patients with immune-mediated rheumatic diseases. We discuss putative mechanisms of frailty relevant to these diseases, tools for frailty measurement, and potential implications of frailty assessment for clinical care. We also explore the complex inter-relationship between frailty, inflammation, and disease activity in immune-mediated rheumatic diseases. As insight is gained into the epidemiology and mechanisms of frailty among patients with immune-mediated inflammatory rheumatic diseases, the possibility of targeting frailty with an intervention that could complement standard disease-modifying therapies to prevent adverse outcomes and improve health-related quality of life becomes closer to reality.

CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis. We present a detailed analysis of the effects of CD19-targeting CAR T-cell therapy in patients with systemic sclerosis.

The global population is ageing and the rheumatology workforce should be prepared to take care of the inevitable complexities of ageing patients. We can learn from our colleagues and experts in geriatrics about how best to manage multimorbidity, polypharmacy, geriatric syndromes, and shifting priorities of older patients in the context of delivering care for rheumatic diseases. One approach to learning and adopting key ageing constructs within rheumatology practice is to incorporate the established Geriatric 5Ms-principles fundamental to caring for older adults. In this Series paper we discuss the 5Ms in the context of rheumatology practice (1) multicomplexity: assessing and managing multimorbidity and challenging biopsychosocial situations, (2) medications: ensuring that medications do not interfere with the other Ms, (3) mind: managing neurocognitive disorders and comorbid mental health conditions, (4) mobility: ensuring older adults can move independently and safely, and (5) what matters most: aligning care with an older adult's specific goals.

Chimeric antigen receptor (CAR) T cells have recently shown remarkable promise in treating rheumatic diseases, including systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies, and systemic sclerosis. Currently, there are 37 clinical trials registered for CAR T-cell therapy in rheumatic diseases and many more are being planned. Much of this enthusiasm is justifiable, but widespread adoption of CAR T-cell therapy in rheumatology faces several barriers. The trajectory of autoimmune diseases differs from malignancies and a surprisingly narrow population could be eligible for CAR T-cell therapy. Current CAR T-cell approaches rely on B-cell depletion, which has a mixed record of success for many diseases. The high cost of CAR T-cell therapy and potential safety concerns, such as cytokine release syndrome and long-term infection risks, also pose substantial challenges. Moving forward, more targeted CAR T-cell approaches, such as antigen-specific chimeric autoantibody receptors or chimeric autoantigen T-cell receptors, could offer greater efficacy and safety in treating rheumatic diseases.

The effect of nirmatrelvir-ritonavir on post-COVID-19 outcomes for individuals who are immunocompromised is understudied. We aimed to examine the association of nirmatrelvir-ritonavir with post-acute sequelae and mortality among patients who are immunocompromised and admitted to hospital with COVID-19.

Proximod is a selective agonist of sphingosine-1-phosphate receptor-1 (S1PR1). It acts by redirecting lymphocytes from the circulation to secondary lymph nodes, and is under development as an immunomodulator for rheumatoid arthritis. We aimed to evaluate the safety, pharmacokinetics, and preliminary efficacy of proximod in healthy volunteers and patients with rheumatoid arthritis.

IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease. Absence of disease awareness among primary care physicians and specialists without expertise in IgG4-related disease remains the main cause of diagnostic delay. We aimed to identify red flags that might increase the suspicion of IgG4-related disease in primary and secondary care settings. A task force of experts in IgG4-related disease from the European Reference Network for Rare Connective Tissue Diseases (ERN-ReCONNET), patient representatives, and primary care physicians derived potential red flags for IgG4-related disease through a systematic literature search and a level of agreement exercise. Five red flags reached 100% agreement among experts: swelling in one or more organ system; pancreatic and biliary tree involvement; increased serum IgG4; IgG4 plasma cell tissue infiltration; and obliterative phlebitis. Red flags for IgG4-related disease are intended for use in primary and secondary care to improve referral to centres of expertise and prompt early diagnosis.

The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE.

With rising health-care expenditures and workforce shortages, sustainable alternatives to traditional outpatient follow-up strategies are required to optimise care efficiency. We aimed to investigate the cost-effectiveness and clinical effectiveness of patient-initiated follow-up (PIFU) supported by asynchronous telemedicine for patients with spondyloarthritis compared with usual care in daily practice.