Matteson, Eric L.

ObjectiveThe objective of this study is to compare biologic drug discontinuation rates for older‐ versus younger‐onset rheumatoid arthritis (YORA) because this is a key outcome measure that could impact prescribing practices.MethodsWe performed a retrospective medical record review of all patients who fulfilled the 1987 American College of Rheumatology (ACR) criteria for adult‐onset rheumatoid arthritis (RA) in 1999‐2013 among residents of a geographically defined area, with follow‐up until death, migration, or July 1, 2017. Discontinuation rates were estimated using cumulative incidence adjusted for the competing risk of death.ResultsA total of 240 cases of elderly‐onset rheumatoid arthritis (EORA) and 366 cases of YORA were identified (65% and 73% female, respectively; P = 0.025). Cumulative incidence of biologic initiation was lower among the EORA cohort compared with the YORA cohort (18% vs 33%, respectively, at 10 years after RA incidence; P < 0.001). Among those treated with a biologic, years from RA diagnosis to first biologic treatment was not significantly different between the two groups (P = 0.62). Drug survival of first biologic was 64% at 1 year (95% confidence interval [CI]: 45%‐77%) and 53% at 2 years (95% CI: 33%‐66%) for EORA, compared with 61% at 1 year (95% CI: 50%‐69%) and 45% at 2 years (95% CI: 34%‐53%) for YORA (P = 0.75). Concurrent glucocorticoid use at initiation of first biologic was statistically and significantly associated with a lower risk of discontinuation in EORA (hazard ratio 0.21; 95% CI: 0.08‐0.53) but not in YORA (interaction P = 0.04).ConclusionDrug survival rates of biologic medications did not differ significantly between patients with EORA and YORA.

Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that characteristically causes joint inflammation and damage. In addition, many patients develop extraarticular manifestations which may cause significant comorbidity and premature mortality.Some respiratory tract involvement of the upper and lower airways and parenchymal disease features are unique to RA, including cricoarytenoid arthritis and RA pulmonary nodulosis, and others, especially the interstitial parenchymal involvement, occur in many other idiopathic and autoimmune diseases. The pathophysiology of lung disease is not well understood. Rheumatoid lung disease may even predate the onset of joint disease, and could be triggered by chronic airway and alveolar epithelial injury. Chronic systemic inflammation and risk factors such as cigarette smoking, infection, host genetics, and immune dysregulation are contributors. Treatment of the respiratory disease is directed at reducing the systemic inflammation of RA. Less well understood is the management of the interstitial lung disease of RA, for which antifibrotic and immune suppressive agents may be helpful. The management of RA-related lung disease is perhaps the major remaining hurdle in reduction of the disease burden related to extraarticular manifestations of this disease.

Objective To estimate the annual incidence and prevalence of and frequency of mortality associated with antiphospholipid syndrome ( APS ). Methods An inception cohort of patients with incident APS in 2000–2015 from a geographically well‐defined population was identified based on comprehensive individual medical records review. All cases met the 2006 Sydney criteria for APS (primary definition) or had a diagnosis of APS confirmed by physician consensus (secondary definition). Levels of lupus anticoagulant, IgM and IgG anticardiolipin antibodies, and anti–β2‐glycoprotein I antibodies were tested in a centralized laboratory. Incidence rates were age‐ and sex‐adjusted to the 2010 US white population. Prevalence estimates were obtained from the incidence rates, assuming that there was no increased mortality associated with APS and that migration in or out of the area was independent of disease status. Results Among this cohort in 2000–2015, 33 cases of incident APS , as defined by the Sydney criteria, were identified (mean age of patients 54.2 years; 55% female, 97% white). The annual incidence of APS in adults ages ≥18 years was 2.1 (95% confidence interval [95% CI ] 1.4–2.8) per 100,000 population. Incidence rates were similar in both sexes. The estimated prevalence of APS was 50 (95% CI 42–58) per 100,000 population, and was similar in both sexes. Six patients (18%) had a concurrent diagnosis of systemic lupus erythematosus. The most frequent clinical manifestation was deep vein thrombosis. The overall frequency of mortality among patients with APS was not significantly different from that in the general population (standardized mortality ratio 1.61, 95% CI 0.74–3.05). Conclusion APS occurred in ~2 persons per 100,000 population per year. The estimated prevalence was 50 per 100,000 population. Overall mortality was not notably different from that observed in the general population.

Interleukin (IL)-17 is a T helper 17 cytokine implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Although IL-17A has a well-established role in murine pulmonary fibrosis models, its role in the tissue remodeling and fibrosis occurring in idiopathic pulmonary fibrosis (IPF) and RA-associated interstitial lung disease (RA-ILD) is not very well defined. To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with IPF and RA-ILD to determine IL-17A receptor (IL-17RA) expression. Both normal and pathogenic IPF lung fibroblasts express functional IL-17RA and respond to IL-17A stimulation with cell proliferation, generation of extracellular matrix (ECM) proteins, and induction of myofibroblast transdifferentiation. Small interfering RNA (siRNA) silencing of IL-17RA attenuated this fibroblast response to IL-17A on ECM production. These fibroblast responses to IL-17A are dependent on NF-κB-mediated signaling. In addition, inhibiting Janus activated kinase (JAK) 2 by either siRNA or a selective pharmacological inhibitor, AZD1480—but not a JAK1/JAK3 selective inhibitor, tofacitinib—also significantly reduced this IL-17A-induced fibrogenic response. Lung biopsies of RA-ILD patients demonstrate significantly higher IL-17RA expression in areas of fibroblast accumulation and fibrosis, compared with either IPF or normal lung tissue. These observations support a direct role for IL-17A in lung fibrosis that may be particularly relevant in the context of RA-ILD.