Effectiveness and safety of filgotinib in rheumatoid arthritis patients: data from the GISEA registry.

OBJECTIVES: The aim of this study was to evaluate the effectiveness and safety profile of filgotinib, a JAK1 preferential inhibitor, in rheumatoid arthritis (RA) patients included in Italian GISEA (Group for the Study of Early Arthritis) registry. METHODS: Data from RA patients treated with filgotinib, recorded in the GISEA registry, were analysed. Disease activity scores and patient-reported outcomes (PROs) were assessed at baseline, as well as during 12-month follow-up. A difficult-to-treat (D2T) RA patient was defined according with EULAR criteria. Retention rate of filgotinib was estimated by the Kaplan-Meier method and factors influencing drug discontinuation were estimated by Cox regression models. RESULTS: 246 RA patients (female 89%, 57.6±12.2 years old) started filgotinib, mostly as second (22%) or further (43.9%) b/tsDMARDs line of treatment. At 3 and 12 months, 18.8% and 27.5% of patients achieved Clinical Diseases Activity Index based remission and 30.1% and 37.7% obtained a visual analogue scale of pain ≤20 (all p<0.01 vs. baseline). Filgotinib survival rate was 84.5% at the 6-month and 75.8% at 12-month follow-up, and was comparable either in monotherapy or combination therapy, and irrespective of glucocorticoid intake. b/tsDMARD naive patients had the lowest hazard ratio (HR) of filgotinib discontinuation (HR 0.29, 95%CI 0.14-0.64), while D2T-RA the highest (HR 1.82, 95%CI 1.01-3.3). Eight patients (3.3%) discontinued filgotinib due to adverse events. CONCLUSIONS: In an Italian real-life setting, filgotinib is confirmed to be safe and with a good effectiveness profile both in monotherapy and without glucocorticoids.

Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry.

Objectives: An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. Methods: RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. Results: A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). Conclusion: We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory.

The Systemic Score May Identify Life-Threatening Evolution in Still Disease: Data from the GIRRCS AOSD-Study Group and the AIDA Network Still Disease Registry.

OBJECTIVE: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. RESULTS: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. CONCLUSION: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.

Autoantibody-negative rheumatoid arthritis: still a challenge for the rheumatologist.

Increased research over the past 30 years has greatly improved the understanding of the pathophysiological mechanisms and clinical aspects of autoantibody-positive rheumatoid arthritis, resulting in improved management and outcomes. In contrast, the subset of rheumatoid arthritis that does not have autoantibodies (such as rheumatoid factor and anti-citrullinated protein autoantibodies) remains less well defined in its pathogenic mechanisms. Autoantibody-negative rheumatoid arthritis continues to pose diagnostic challenges, might respond differently to therapies, and appears to be burdened with different comorbidities and outcomes. The clear separation of rheumatoid arthritis according to serotypes is still a subject of uncertainty and controversy, and studies specifically focused on comparing rheumatoid arthritis and rheumatoid arthritis-like arthritides that do not have autoantibodies remain scarce. The purpose of this Review is to summarise the peculiarities that make autoantibody-negative rheumatoid arthritis different from its autoantibody-positive counterpart, with the aim of generating debate and stimulating further research on this challenging condition.