Clinical and experimental rheumatology最新文献

Objectives: To evaluate the cost-effectiveness of avacopan plus immunosuppressants versus glucocorticoid (GC)-based regimens for adults with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in China, and to estimate the maximum avacopan unit price consistent with willingness-to-pay (WTP) thresholds.

Methods: A nine-state Markov model (active disease; three remission states; three relapse states; end-stage renal disease [ESRD]; death) was developed from the Chinese healthcare system perspective. Baseline characteristics were derived from the ADVOCATE trial. The intervention was avacopan plus cyclophosphamide (CYC) or rituximab (RTX) with reduced-dose GCs; the comparator was CYC/RTX plus standard GCs. Treatment shares followed trial allocation (35.2% CYC; 64.8% RTX). Outcomes included total costs, life-years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs), using a WTP threshold of one time China's 2024 GDP per capita per QALY. Uncertainty was assessed through one-way, probabilistic, and scenario analyses. Threshold price analyses back calculated the avacopan unit price at WTPs of one time, 1.2 times, and 1.5 times GDP per capita.

Results: Avacopan increased QALYs (5.81 vs. 5.26) and LYs (8.25 vs. 7.77) and increased total costs ($73,478 vs. $70,110), yielding an ICER of $6,146/QALY. At a WTP of $13,445/QALY, avacopan was cost-effective; results were robust in sensitivity and scenario analyses. The maximum cost-effective price was $11.12-$12.70 per 10 mg at WTPs of 1.0-1.5 times GDP per capita.

Conclusions: Avacopan-based regimens are cost-effective versus GC-based therapy for GPA/MPA in China and support value-based pricing of $11.12-$12.70 per 10 mg.

Objectives: Vitamin D deficiency has been linked with several autoimmune diseases. Data are limited in anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV), and it is unknown whether vitamin D could have a therapeutic role in AAV.

Methods: The prospective, pragmatic, non-randomised exploratory PRAVDA study with ITT and pre-protocol analyses aimed to enrol >100 patients with AAV at the Vasculitis Clinic (Toronto, Canada) from January to July 2021. 25-hydroxyvitamin D [25(OH)D] was measured at baseline by ELISA. Patients with low 25(OH)D (<75 nmol/L at baseline) were asked to increase vitamin D supplementation by 1000 IU/day (to a maximum 2000 IU/day). 25(OH)D was measured again at month 12. The primary endpoint was 12-month disease relapse. Secondary analyses included correlations between vitamin D status and disease-specific clinical features.

Results: The study included 101 patients, 41 (40.6%) of whom had low baseline vitamin D levels and were asked to increase vitamin D3 intake. Of these patients, 32 had vitamin D level reassessed at month 12; 62.5% (20/32) had achieved normal levels. Relapse rates at month 12 were similar between patients with low (n=3/41; 7.3%) and normal (n=6/60; 10%; p=0.64) baseline vitamin D levels. However, no relapses were observed in patients who corrected baseline vitamin D deficiency.

Conclusions: These findings can help designing larger studies on vitamin D supplementation in AAV patients, focusing mostly on those vitamin D deficient at baseline.

Objectives: To report pregnancy outcome and neonatal immune parameters following early conception after maternal CD19 chimeric antigen receptor T-cell (CAR-T) therapy for refractory systemic lupus erythematosus (SLE).

Methods: Maternal and neonatal CAR-T cells were assessed by transgene polymerase chain reaction (PCR) at delivery. CD19+ B-cell counts and immunoglobulin levels were measured in maternal and neonatal blood at birth. Infant health outcomes were assessed during the first year of life.

Results: Conception occurred approximately seven weeks after CD19 CAR-T infusion. CAR-T cells were not detected in maternal peripheral blood or cord blood at delivery. Neonatal CD19+ B-cell counts and IgG levels were within age-appropriate reference ranges and exceeded maternal values, which remained subnormal. During one year of follow-up, the infant experienced no recurrent or severe infections.

Conclusions: This case represents the earliest reported pregnancy following CD19 CAR-T therapy for SLE and the first to include neonatal immune assessment at birth. No evidence of transplacental CAR-T transfer or clinically significant neonatal immunodeficiency was observed. Additional cases and long-term follow-up are required to guide reproductive counseling after CAR-T therapy.

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by persistent synovial inflammation. Janus kinase inhibitors (JAKi) are effective targeted therapies for RA, yet clinical responses vary. We aimed to identify genetic predictors of JAKi effectiveness in Taiwanese patients with RA.

Methods: In this retrospective study, 275 RA patients treated with tofacitinib, baricitinib, or upadacitinib in the Taiwan Precision Medicine Initiative (TPMI) were recruited and classified as Effective or Non-effective. Fifty-eight candidate single-nucleotide polymorphisms (SNPs) were evaluated using existing Taiwan Biobank v2 array data. We integrated cell-type-specific eQTL resources (scQTLbase) and single-cell RNA sequencing (scRNA-seq) to support gene-level associations.

Results: In this cohort (Effective, n=217; Non-effective, n=58), CCL2 rs1024611/rs4586 and ITPA rs1127354 were the top nominal candidates (all p<0.05). In scQTLbase (GRCh38), rs1024611 associated with higher CCL2 in dendritic cells, and rs1127354 with higher ITPA in CD14+ monocytes. scRNA-seq showed higher CCL2 in Non-effective patients (p<0.001), predominantly across M0/M1/M2 monocytes. ITPA was higher in Effective patients (p=0.018), most notably in M2 monocytes (p<0.001), with elevated ITPA also observed in M1 monocytes of Non-effective patients (p 0.004).

Conclusions: Our data prioritise CCL2 and ITPA as candidate pharmacogenetic signals for JAKi response. Given the use of a persistence-based effectiveness endpoint and the exploratory nature of secondary EULAR-based outcome assessments, independent replication using standardised ACR/EULAR outcomes is warranted.

Objectives: Juvenile idiopathic arthritis (JIA) leads to significant long-term morbidity from articular and extra-articular complications, yet the burden of comorbidities in adults with long-standing disease is not well characterised. This study aimed to determine the prevalence and incidence of key comorbidities in adults with JIA and assess their association with demographic and clinical features.

Methods: We performed a national multicentre retrospective cohort study using data from adults with JIA, defined by the 2001 ILAR criteria, enrolled in the Portuguese Rheumatic Diseases Register (Reuma.pt). Demographic and clinical data, along with comorbidities, were collected. Comorbidities included cardiovascular disease, hypertension, dyslipidaemia, diabetes, thyroid disease, amyloidosis, inflammatory bowel disease, allergy and asthma, osteoporosis, psychiatric disease, and autoimmune disease. Rare conditions were grouped into broader categories. Extra-articular JIA manifestations were excluded. Incidence rates were calculated as the number of new events per 1,000 person-years (95% CI), and prevalence was assessed using frequencies.

Results: The cohort included 748 patients, 65.6% female, with a median age of 27.7 years and a median disease duration of 20.6 years. Oligoarticular JIA was the most common subtype (29.9%). Autoimmune diseases had the highest incidence rate (7.1/1,000 person-years), followed by hypertension (5.1/1,000 person-years) and psychiatric disease (4.0/1,000 person-years). Hypertension (9%), psychiatric disease (8%), and osteoporosis (5%) were the most prevalent comorbidities. Biologic DMARD use was associated with reduced risk of psychiatric disease (OR=0.38, p=0.03), and no significant association with malignancy or infection was found.

Conclusions: JIA patients with long-standing disease frequently develop comorbidities, particularly hypertension. Biologic therapy seems to reduce the risk of comorbidities. Long-term monitoring of comorbidities in JIA patients is paramount.

Central memory T (TCM) cells are a cornerstone of the adaptive immune system, serving as a long-lived, self-renewing stem-like population that provides durable immunological protection. Primarily residing in secondary lymphoid organs, TCM cells are characterised by robust proliferative potential, multipotent differentiation capacity, and metabolic reliance on oxidative phosphorylation. These attributes are crucial for mediating rapid and effective secondary immune responses.Recent advances have elucidated the complex molecular circuitry governing TCM cells' fate decisions, focusing on the transcription factor networks and epigenetic modifications that preserve their characteristic stemness. In the context of disease, TCM cells play a dual role: they are a vital source of effector cells for combating infections and malignancies, yet they can also contribute to the chronic inflammation that drives autoimmune disorders including systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, and Sjögren's disease.This functional dichotomy underlies their considerable clinical significance. Notably, TCM cells represent a preferred cellular source for chimeric antigen receptor T (CAR-T) cell therapy in both oncology and emerging autoimmune indications, serve as a predictive biomarker for the efficacy of immune checkpoint inhibitors, and act as a key indicator of vaccine effectiveness.This review comprehensively examines TCM cells, covering their biological features, developmental mechanisms, and recent clinical applications in cancer immunotherapy, autoimmune diseases, and cellular therapies, while outlining future therapeutic directions.

Objectives: Interstitial lung disease (ILD) is one of the most common manifestations of systemic sclerosis (SSc), with most patients requiring treatment with immunosuppressive or anti-fibrotic agents to control ILD progression. Since gastrointestinal (GI) tract complications are widespread in this patient setting, we focused on their prevention and management.

Methods: We conducted a modified Delphi study following best practices for consensus studies. We involved 20 expert rheumatologists from 8 Italian regions in two online rounds conducted between April and September 2024.

Results: An agreement of at least two-thirds of panellists was achieved on most topics explored, including the need for a preliminary evaluation of GI status in patients with SSc-ILD undergoing anti-fibrotic therapy (100% agreement), taking into account the presence of pre-existing diarrhoea (100%), weight loss (95%) and nausea/loss of appetite (100%), the definition of specific tests and exams for these conditions, the need of informing patients on potential GI complications (100%) and nutritional preventive advice (85%), and the monitoring of GI status during anti-fibrotic therapy (100%), at 3-month intervals (75%). Further, dose-reduction of anti-fibrotic therapy and, if needed, temporary discontinuation, was agreed in presence of side effects including diarrhoea (95%) or weight loss (85%). In the presence of nausea or loss of appetite, dose-reduction was also agreed, with no immediate need for drug discontinuation (90%).

Conclusions: This study provided a detailed list of expert-based recommendations to guide everyday clinical practice of SSc-ILD, though prospective validation is needed to confirm their effectiveness in preventing and managing GI side effects.