Lancet Rheumatology最新文献

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.

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.

Background: 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.

Methods: Six patients with severe diffuse systemic sclerosis with an insufficient response to at least two treatments were consecutively recruited at the Department of Internal Medicine 3, University Hospital Erlangen (Erlangen, Germany) to receive CD19-targeting CAR T-cell treatment (1 × 10⁶ CAR T cells per kg bodyweight). Events were predefined by progression of interstitial lung disease, onset of congestive heart failure, onset of renal failure, onset of arterial hypertension, or initiation of new immunosuppressive or antifibrotic therapy. Event-free time or treatment intensification after study entry was the primary outcome. Key secondary outcomes included changes in the modified Rodnan Skin Score (mRSS), imaging (a component of the assessment of lung fibrosis), laboratory assessments, patient-reported outcomes, and a modified version of the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline, 3 months, 6 months, 9 months, and 12 months.

Findings: Between April 20, 2022, and Nov 8, 2023, six patients with severe diffuse systemic sclerosis (median age 42 years [IQR 36-53]; four men and two women; all White European) were recruited and received CD19-targeted CAR T-cell therapy. The median follow-up time was 487 days (IQR 342-585). No events occurred within the observational period. Probability of improvement in the ACR-CRISS score increased to a median of 100% (IQR 100-100) at 6 months. Median mRSS decreased by 31% (IQR 29-38), corresponding to a median of 8 points (IQR 7-13) within 100 days. The extent of disease on CT scan decreased by a median of 4% (IQR 3-4) due to reduction of ground-glass opacities while the reticular pattern remained stable. Forced vital capacity improved by a median of 195 mL (IQR 18-275) at the latest observational timepoint.

Interpretation: We provide the first evidence that CD19-targeting CAR T-cell therapy might intercept with the progression of fibrotic organ manifestations in patients with systemic sclerosis.

Funding: Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN-Foundation Erlangen, IZKF Erlangen, and Bundesministerium für Bildung und Forschung.

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.