Cynthia S. Crowson

Objective: Glucocorticoids (GCs) remain the primary treatment for polymyalgia rheumatica (PMR) but are associated with substantial long‐term toxicity. Although sex‐based differences in GC‐related adverse effects have been suggested, they have not been well studied in PMR. Methods: We conducted a retrospective cohort study of patients with PMR treated between 2017 and 2024 within a multisite health system. Patients ≥50 years of age with at least two PMR International Classification of Diseases, Tenth Revision, codes and documented GC dosing for ≥75% of days during the first six months of treatment were included. Sex‐based differences in GC toxicity outcomes including incident or worsening hypertension, type 2 diabetes mellitus, and incidence of fragility fractures were evaluated using multivariable regression models adjusted for age, body mass index, treatment site, and baseline type 2 diabetes mellitus. Results: A total of 1,899 patients met inclusion criteria (915 female patients and 984 male patients; mean age 72.5 years). At one year, the cumulative GC exposure and composite toxicity was not statistically different between sexes. At three years, cumulative GC exposure was higher in female patients (4,419.5 mg prednisone equivalents compared to 4,106.2 mg in male patients, P = 0.042) as well as daily GC dose ( P = 0.037). Female patients had a higher incidence of fractures at three years (8.5% vs 3.2%, P ≤ 0.001) and incidence of giant cell arteritis (GCA; 7.6% vs 3.4%, P < 0.001). Conclusion: The median cumulative GC exposure in patients with PMR remains high, with higher exposure in female patients. Female patients were more likely to experience fracture and the development of GCA within the same time frame. image

To report population-level data describing long-term trends in remission, sustained remission and relapse among patients with rheumatoid arthritis (RA). We conducted a population-based inception cohort study of adults with incident RA in Olmsted County, Minnesota, USA, meeting 1987 or 2010 ACR criteria between 1990 and 2019. Patients were followed through 31 December 2023. We estimated cumulative incidence of first remission, sustained remission (≥6 months) and relapse after remission, accounting for competing risk of death. Cox models comparing calendar periods were adjusted for age, sex, baseline body mass index and serostatus. Among 1179 patients followed for a median of 9.4 years, 816 achieved remission and 630 achieved sustained remission. One-year remission, defined by our prespecified criteria, increased from 12.8% in 1990–1999 to 26.4% in 2010–2019. Median time to remission shortened from 6.4 years to 2.8 years. Despite these gains, relapse within 5 years after remission increased from 62.8% in 1990–1999 vs 79.2% in the 2010–2023 period. Remission in RA has become earlier and more frequent over time, but durability has not improved. Strategies to sustain remission remain a critical unmet need.

Objective: The aim of this study was to compare infection‐related hospitalization risk among patients with nonrenal systemic lupus erythematosus initiating commonly used immunosuppressants. Methods: We emulated a target trial using Optum Labs Data Warehouse claims to compare the risk of infection‐related hospitalization among patients initiating azathioprine, belimumab, methotrexate, or mycophenolic acid analogues (MPAAs) between March 2011 and September 2023. We excluded patients with prior lupus nephritis, solid‐organ or bone marrow transplantation, or rituximab/cyclophosphamide exposure. The primary outcome was time to first infection‐related hospitalization using intention‐to‐treat (ITT) and per‐protocol (PP) analyses. We applied inverse probability of treatment weighting to account for baseline covariates and fitted marginal structural Cox models incorporating time‐varying monthly glucocorticoid dose during follow‐up. Results: Among 6,168 patients, 24‐month cumulative incidence of infection‐related hospitalization was 10% (95% confidence interval [CI] 8–12) for azathioprine, 8% (95% CI 5–10) for belimumab, 10% (95% CI 8–11) for methotrexate, and 13% (95% CI 10–15) for MPAAs. In ITT analyses, MPAAs had higher risk than belimumab (hazard ratio [HR] 1.55, 95% CI 1.07–2.25) and methotrexate (HR 1.32, 95% CI 1.04–1.68). In PP analyses, azathioprine (HR 2.04, 95% CI 1.01–4.16) and MPAAs (HR 2.27, 95% CI 1.11–4.62) had higher risk compared with belimumab. After accounting for time‐varying monthly glucocorticoid dose, between‐treatment differences were no longer significant. Conclusion: Initial differences in the infection‐related hospitalization risk were attenuated after accounting for time‐varying glucocorticoid exposure. These findings highlight glucocorticoid exposure as an important factor associated with serious infection risk while recognizing that postbaseline glucocorticoid use may reflect both evolving disease activity and a pathway through which therapies influence infection risk. image

Objective: To evaluate the efficacy of cytokine‐directed therapies in VEXAS (vacuoles, E1 enzyme, X‐linked, autoinflammatory somatic) syndrome using previously proposed treatment response criteria. Methods: All patients with genetically confirmed VEXAS syndrome who received targeted therapies with JAK inhibitors (JAKi), tumor necrosis factor α inhibitors (TNFαi), or interleukin‐1 (IL‐1) or IL‐6 inhibitors were identified. Clinical and biochemical data were recorded for patients at time of targeted therapy initiation, and at 3‐, 6‐, and 12‐month follow‐up time points. Treatment response was labeled as complete response (CR; normalization of C‐reactive protein [CRP], prednisone 50% improvement in CRP, >50% prednisone dose reduction, improvement or resolution of disease features), treatment failure (TF; worsening CRP, increasing prednisone, worsening of disease features), or no response (not meeting criteria for CR, PR, or TF). Results: Overall, 52 patients received an IL‐1i, IL‐6i, or JAKi therapy. At six‐month follow‐up, 3 of 19 IL‐6i patients experienced CR, 4 of 19 experienced PR, and 7 of 19 experienced TF. 2 of 17 patients receiving JAKi experienced CR, 3 of 17 experienced PR, and 6 of 17 experienced TF. No patients receiving IL‐1i or TNFαi experienced CR, and only 1 of 5 IL‐1i patients experienced PR. Among those still receiving biologic therapy at 12 months, only 1 of 11 receiving IL‐6i and 0 of 7 receiving JAKi experienced CR. Conclusion: IL‐6i and JAKi therapies demonstrated limited, unsustained efficacy for management of VEXAS syndrome. IL‐1i and TNFαi therapies were not efficacious. Useful application of previously reported treatment response criteria was demonstrated, but future incorporation of hematologic parameters may be beneficial.

Objective: This study evaluated sequential multi-site fine-tuning of large language models (LLMs), simulating incremental deployment across institutions for extracting mobility functional status from unstructured clinical notes. Materials and Methods: We assembled a corpus of 600 clinical notes from 3 institutions, yielding 3810 annotated note sections (1200 training; 2610 testing). Building upon our previously established LLM mobility extraction pipeline, which utilized optimized prompt engineering, we applied parameter-efficient low-rank adaptation (LoRA) fine-tuning. We evaluated sequential multi-site fine-tuning, where the model is trained locally and only the updated LoRA weights are transferred to the next site. We compared this against joint fine-tuning, which requires pooling all multi-site patient data centrally before training. Performance was measured by micro F1-scores for 2 distinct subtasks: mobility extraction and impairment classification. Results: Sequential multi-site fine-tuning yielded comparable results to centralized joint fine-tuning for mobility extraction (F1, 0.861 vs 0.894) and impairment classification (F1, 0.912 vs 0.900). Both sequential and joint fine-tuning outperformed an untuned 70B model. Additionally, single-site LoRA models showed robust cross-site generalization. Discussion: Sequential multi-site fine-tuning offers a resource-friendly approach to adapt LLMs to clinical environments. By retaining previously acquired knowledge without severe interference, this strategy allows for local fine-tuning at each institution without the need to pool or share sensitive patient data required for joint fine-tuning. Conclusion: Sequential multi-site fine-tuning provides a viable solution for the scalable, incremental deployment of LLMs across institutions, showing promising generalizability for clinical information extraction from electronic health record narratives.

Objective: We aim to identify risk factors to enable stratification of patients' susceptibility to inflammatory arthritis immune‐related adverse events (IA‐irAEs). This retrospective study mainly examines whether preexisting osteoarthritis (OA) increases the likelihood of de novo IA‐irAEs. Methods: The prevalence of OA among immune checkpoint inhibitor (ICI)–treated patients who developed IA‐irAE, those who developed other types of irAEs but not IA (non‐IA irAEs), and those who did not develop any irAEs (non‐irAEs) were compared. Electronic medical records were reviewed to extract demographic, clinical, and laboratory data. Group comparisons and logistic regression analyses were performed. Results: A total of 181 de novo IA‐irAE patients, 140 non‐IA irAE patients, and 170 non‐irAE patients were included. The prevalence of OA was significantly higher in the IA‐irAE group (69%) than in the non‐IA irAE group (48%) and the non‐irAE group (48%) (both P < 0.001). The IA‐irAE group demonstrated a higher frequency of multisite OA, with more predominant hand involvement (62%) than the non‐IA irAE with OA group (13%) and the non‐irAE with OA group (13%) (both P < 0.001). A family history of autoimmune disease (AID) (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.02–4.05), preexisting OA (OR 2.88, 95% CI 1.85–4.52), and melanoma (OR 2.63, 95% CI 1.56–4.47) were identified as risk factors for the development of IA‐irAE. Conclusion: OA was more prevalent among ICI‐treated patients developing IA‐irAE than those who were not. Hand OA was the most common OA pattern in IA‐irAE patients. Preexisting OA, melanoma, and a family history of AID were associated with IA‐irAE.

Rheumatoid arthritis (RA) is associated with a wide spectrum of comorbidities that substantially influence quality of life and long-term outcomes. These include extra-articular manifestations, cardiovascular disease, cerebrovascular accidents, dementia, malignancy, infection, mental health disorders and osteoporosis. Patterns of comorbidity in RA have evolved over the past three decades, with declining prevalence of some complications alongside persistently high or increasing burdens of interstitial lung disease, anxiety and depression. Shifts in the comorbidity landscape probably reflect advances in RA management, including the expanded use of biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) and a widespread adoption of treat-to-target strategies. Consideration of comorbidity-specific epidemiology, the potential effect of DMARDs on comorbidity risk and opportunities to address both RA and comorbid disease are increasingly relevant in clinical care. Preventive strategies, including selected enhanced screening approaches such as those for cervical cancer, interstitial lung disease, cardiovascular disease and osteoporosis, form an important component of comprehensive RA management. Awareness of the changing comorbidity landscape could support more integrated and individualized care for people with RA.