ACR open rheumatology最新文献

Objective: To assess the impact of renal replacement therapy in people with lupus nephritis (LN)-associated end-stage kidney disease (ESKD) and support the development of the 2024 American College of Rheumatology LN treatment guidelines.

Methods: We conducted a systematic literature review and meta-analysis to address three Population, Intervention, Comparison, and Outcome (PICO) questions related to renal replacement therapy for ESKD due to LN, including comparisons of kidney transplant versus dialysis, hemodialysis versus peritoneal dialysis, and preemptive kidney transplant versus no preemptive kidney transplant. Outcomes of interest included mortality, cardiovascular (CV) events, infections, lupus flares, disease-related damage, graft failure, and quality of life. We conducted a meta-analysis and analyzed hazard ratios for time-to-event analyses and risk ratios for dichotomous outcomes, as well as absolute risk estimates.

Results: Sixteen comparative observational studies addressed at least one of the three PICO questions. Kidney transplant was found to reduce the risks of all-cause mortality, CV mortality, infection-related mortality, and CV events compared with dialysis (high certainty). Dialysis modality (peritoneal vs hemodialysis) was not associated with mortality (high certainty) or with other outcomes of infection, CV complications, and systemic lupus erythematosus flares (low certainty). Preemptive kidney transplant was associated with lower risks of graft failure and mortality (low certainty).

Conclusion: This systematic review identified improved outcomes with kidney transplant versus dialysis for people with LN-associated ESKD and potential benefits of preemptive kidney transplant. This evidence supports the use of kidney transplant as a preferred renal replacement therapy for people with LN-ESKD.

Objective: Mycophenolate mofetil (MMF) can stabilize or improve lung function in systemic sclerosis-related interstitial lung disease (SSc-ILD). We hypothesized that combining MMF with pirfenidone (PFD) would produce a significantly more rapid and/or greater improvement in lung function.

Methods: A randomized (1:1), double-blind, placebo (PLA)-controlled phase 2 trial was conducted in SSc-ILD in which patients received PFD or PLA (801 mg three times daily) along with MMF (1,500 mg twice daily) for 18 months. The primary outcome was change in percent predicted forced vital capacity (FVC-%). Linear mixed-effects models assessed treatment differences in a modified intention-to-treat population.

Results: Only fifty-one of 150 intended subjects (34%) were randomized (MMF+PLA, n = 24; MMF+PFD, n = 27). The FVC-% improved from baseline to 18 months by 2.24 ± 1.35 (least-squares mean [LSM] ± SEM) in the MMF+PLA group and 2.09 ± 1.28 in the MMF+PFD group (LSM treatment difference -0.14; P = 0.93). Median time to achieve a ≥3% improvement in FVC-% was numerically faster in the MMF+PFD versus MMF+PLA group (12.3 vs 17.8 months, respectively), but the difference was not significant (P = 0.33). For secondary outcomes, only the change over 18 months in the Patient-Reported Outcomes Measurement Information System 29-item physical function score, favoring MMF+PFD, reached statistical significance (P = 0.04). Although other related patient-reported outcomes (PROs) numerically favored the MMF+PFD group, as did quantitative high-resolution computed tomography measures of ILD, the differences between groups did not reach statistical significance. Early withdrawals from study medication and adverse events of special interest were numerically greater with MMF+PFD (n = 8 vs 2 and n = 20 vs 7, respectively).

Conclusion: In this underpowered study, there was no statistically significant treatment difference in overall change in FVC-% between groups. MMF+PFD was not as well tolerated as MMF+PLA.

Objective: Rheumatoid arthritis (RA) is a heterogeneous disease, with patients experiencing varied disease courses and responses to treatment. The objective of this study was to apply topic modeling to RA patient electronic health record (EHR) data and determine (1) the clinical topics/subgroups in those with RA before initiation of a biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) and (2) whether the clinical topics were associated with subsequent RA treatment course.

Methods: We studied patients from a validated EHR-based RA cohort who initiated a b/tsDMARD between 2011 and 2019. Diagnoses codes, laboratory data, and medication prescriptions in the year before their first b/tsDMARD initiation were extracted. Latent Dirichlet allocation, a topic modeling method, was applied to define the underlying "topics" representing clinical subgroups. We used multinomial regression to test association between the clinical topic with four previously published treatment trajectories: tumor necrosis factor inhibitor (TNFi) persisters, TNFi to abatacept, and those prescribed multiple b/tsDMARDs enriched with tocilizumab or rituximab.

Results: From the data of 1,102 patients with RA, diagnoses codes, laboratory data, and prescriptions from the year before b/tsDMARD initiation resulted in four main clinical topics/subgroups: (A) RA codes/methotrexate (MTX), (B) arthralgia/osteoarthritis, (C) hypertension (HTN)/cardiovascular (CV) comorbidities, and (D) mood disorders. Those with RA codes/MTX topic were more likely to persist on TNFi. Conversely, those associated with the HTN/CV topic were more likely to cycle through multiple b/tsDMARDs.

Conclusion: Clinical topics derived from the EHR data of patients with RA before b/tsDMARD differentiated future RA treatment course. HTN/CV comorbidities were associated with a future need for multiple b/tsDMARD therapies.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease marked by progressive fibrosis and multi-organ involvement, most notably in the lungs. Among patients with rapidly progressive diffuse cutaneous SSc and interstitial lung disease (ILD), autologous hematopoietic stem cell transplantation (AHSCT) has emerged as one of the most effective disease-modifying strategies to confer a survival benefit in randomized trials. This review summarizes the evidence from randomized controlled trials, mechanistic studies, and real-world data to evaluate the role of AHSCT in SSc, with a focus on ILD and skin outcomes, immune reconstitution, and long-term efficacy. Current controversies, including conditioning intensity, CD34+ selection, and future directions in the field, are discussed.

Objective: Systemic autoimmune conditions are characterized by increased inflammation and high disease burden. Vagus nerve stimulation (VNS) is known to activate the cholinergic anti-inflammatory pathway and can serve as a potential therapeutic modality for autoimmune conditions. This study aimed to conduct a preregistered systematic review to determine the effect of VNS on inflammation in autoimmune conditions, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

Methods: The databases of Medline/PubMed, Web of Science, Scopus, and CENTRAL were searched until September 2, 2024. Data pertaining to changes in inflammatory blood biomarkers and clinical outcomes in patients with autoimmune conditions receiving VNS were extracted. Studies were included if they provided measurements of peripheral blood biomarkers and clinical outcomes. Study screenings and full-text article reviews were conducted in duplicate. The design of the included studies was assessed using the National Health Lung and Blood Institute guidelines.

Results: Twelve clinical trials studying the effect of VNS on rheumatoid arthritis, Crohn disease, polymyalgia rheumatica, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematous, and systemic sclerosis were reviewed. We found that >50% of studies found a reduction in the mean difference of pro-inflammatory cytokine levels before and after VNS (C-reactive protein decreased in 6 of 9 studies; tumor necrosis factor α decreased in 4 of 8 studies) with the most consistent reduction in IL-6 levels (6 of 7 studies).

Conclusion: Although it can be suggested that VNS can decrease markers of pro-inflammation in autoimmune diseases, more clinical studies with robust design and quality are needed to more confidently support VNS as a therapeutic option for autoimmune conditions.

Objective: To evaluate the long-term impacts of a 16-week remotely supervised exercise and weight loss intervention for rheumatoid arthritis (Supervised Weight Loss and Exercise Training in Rheumatoid Arthritis [SWET-RA]).

Methods: In total, 21 older adults with RA completed the SWET-RA parent trial; 17 of 21 completed an exit survey. Approximately two years after study completion, 14 of 19 eligible participants (mean age 68.9 years) returned for the SWET-RA Reunion. Reunion participants completed surveys on sustained health behaviors and barriers to maintenance. Clinical assessments were evaluated relative to pre-intervention values and included anthropometrics, RA disease activity (Disease Activity Score in 28 joints [DAS-28]), blood biomarkers, and patient-reported outcomes.

Results: At study completion, most participants reported improvements in RA (n = 15) and intended to maintain health behaviors (n = 17). At the two-year Reunion, 50% engaged in aerobic activity regularly, whereas resistance training (21.4%) and dietary self-monitoring (14.3%) were less maintained. Barriers included lack of self-motivation and illness. In total, 10 of 14 participants experienced sustained improvements in RA disease activity without increasing medication. Among the 12 not increasing RA medication, DAS-28 C-reactive protein significantly improved (Δ = -1.0 ± SD 0.9, P = 0.002). Cardiometabolic risk, assessed via metabolic syndrome Z score, improved significantly for participants not increasing related medications (Δ = -1.6 ± SD 2.4, P = 0.05).

Conclusion: Two years post-intervention, only half of the older adults with RA maintained aerobic exercise, with fewer sustaining resistance exercise and self-monitoring dietary intake. Nonetheless, compared to pre-intervention, long-term improvements in RA disease activity and cardiometabolic risk were present. These findings support the inclusion of lifestyle programs in comprehensive RA management.

Chimeric antigen receptor (CAR) T-cell therapy, long transformative in oncology, is now rapidly emerging as a frontier in autoimmune rheumatic diseases, particularly systemic lupus erythematosus (SLE), driven by accumulating evidence of deep B-cell depletion, immune "resetting," and durable drug-free remission in early studies, yet its translation into rheumatology demands mastery of formidable logistical, regulatory, clinical, and ethical complexities that span institutional readiness, multidisciplinary team formation, stringent regulatory compliance, sophisticated operational workflows, comprehensive patient selection and education, meticulous clinical management of both classical toxicities (CRS, ICANS, ICAHT) and autoimmune-specific reactions such as LICATS, robust financial and resource planning, and long-term follow-up extending 15 years or more; successful implementation requires coordinated expertise among rheumatologists, hematologist-oncologists, cellular therapy units, pharmacists, research coordinators, and ICU-capable teams, all embedded within disciplined communication structures, harmonized SOPs, validated PROs, biorepository governance frameworks, and adherence to national and international cellular therapy standards; in parallel, investigators must anticipate bottlenecks such as apheresis access, manufacturing slot scarcity, competing trial enrollment, fluctuating SLE phenotypes, and heterogeneity-driven signal variability, while sustaining patient engagement over years through education, navigation support, and transparent risk/benefit communication; finally, collaboration with industry partners, clinical trial networks, and patient-advocacy organizations is essential for overcoming operational barriers, securing financial sustainability, and ensuring ethical stewardship, so that CAR T-cell clinical trials in autoimmunity can be executed safely, rigorously, and with maximal therapeutic promise for patients.

Objective: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is widely used for assessing disease activity in patients with axial spondyloarthritis (axSpA), particularly in settings where markers of inflammation are unavailable. As no consensus on BASDAI cut-off values exists for disease activity states in axSpA, we aimed to develop and validate such cut-offs against external criteria.

Methods: Routine care patients with axSpA initiating a biologic disease-modifying antirheumatic drug in eight European registries were included. Receiver operating characteristic analyses against external criteria were performed to determine optimal BASDAI values for separating remission, low disease activity (LDA), high disease activity (HDA), and very high disease activity (VHDA). Follow-up data at 6 months were used to select BASDAI cut-off values between remission and LDA and between LDA and HDA, whereas baseline data were used to select the cut-off for VHDA. The level of agreement between disease activity states based on BASDAI and Axial Spondyloarthritis Disease Activity Score (ASDAS) cut-off values was assessed using the proportion of discordance and weighted kappa.

Results: In this cohort of 4,633 patients, the optimal BASDAI cut-off values between remission, LDA, HDA and VHDA were estimated to be <1.3, <2.5, and >5.3. The proportions of discordance between BASDAI and ASDAS disease activity states were 27.6% (weighted κ = 0.48) in baseline data and 37.6% (weighted κ = 0.28) in 6-month data.

Conclusion: BASDAI cut-off values for separating remission, LDA, HDA and VHDA were estimated in >4,600 patients. These cut-off values can be used for assessing disease activity and monitoring patients with axSpA, particularly when laboratory markers are unavailable.