Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.

OBJECTIVES: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies. METHODS: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose. RESULTS: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors. CONCLUSIONS: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.

[Easing the patients' trajectories from private practice to hospital: One-year experiment of the RAPIDO project]. / Fluidification du parcours ville-hôpital : analyse de la trajectoire des patients impliqués dans le dispositif RAPIDO après un an de mise en place.

INTRODUCTION: Internal medicine departments manage patients referred by emergency departments or private practitioners. Considering the overcrowding of emergency departments and lack of beds for inpatients, this specialty must be part of an "ambulatory shift", particularly by strengthening the links between community and hospital medicine. Our objective was to evaluate a new care pathway in internal medicine at Nîmes university hospital. METHODS: Our department has developed the RAPIDO project (Réseau d'Aide à la PrIse en Charge Diagnostique et d'Orientation). The referring general practitioner contacts a senior internist on a dedicated phone line. After careful evaluation, he may offer a consultation within 15 days. A summary report is then given to the patient. RESULTS: Between November 2020 and November 2021, 254 patients were seen via RAPIDO. The average call-consultation time period was 6.4 (±4.5) days, for symptoms lasting for 2 weeks to 3 months in 43% (n=109) of cases. The reason for the call was a suspicion of systemic disease in 28% of cases (n=84), or a dysfunction of an organ in 16%. A diagnosis was made in 89% of cases. The budget of the whole procedure was balanced. CONCLUSION: A quick internal medicine consultation pathway for general practitioners seems to be a relevant, feasible and economically viable healthcare trajectory, which can be transposed to any type of healthcare institution, as soon as sufficient human resources are dedicated.

Patients' Baseline Characteristics, but Not Tocilizumab Exposure, Affect Severe Outcomes Onset in Giant Cell Arteritis: A Real-World Study.

Objectives: Giant cell arteritis (GCA) is associated with severe outcomes such as infections and cardiovascular diseases. We describe here the impact of GCA patients' characteristics and treatment exposure on the occurrence of severe outcomes. Methods: Data were collected retrospectively from real-world GCA patients with a minimum of six-months follow-up. We recorded severe outcomes and treatment exposure. In the survival analysis, we studied the predictive factors of severe outcomes occurrence, including treatment exposure (major glucocorticoids (GCs) exposure (>10 g of the cumulative dose) and tocilizumab (TCZ) exposure), as time-dependent covariates. Results: Among the 77 included patients, 26% were overweight (BMI ≥ 25 kg/m2). The mean cumulative dose of GCs was 7977 ± 4585 mg, 18 patients (23%) had a major GCs exposure, and 40 (52%) received TCZ. Over the 48-month mean follow-up period, 114 severe outcomes occurred in 77% of the patients: infections­29%, cardiovascular diseases­18%, hypertension­15%, fractural osteoporosis­8%, and deaths­6%. Baseline diabetes and overweight were predictive factors of severe outcomes onset (HR, 2.41 [1.05−5.55], p = 0.039; HR, 2.08 [1.14−3.81], p = 0.018, respectively) independently of age, sex, hypertension, and treatment exposure. Conclusion: Diabetic and overweight GCA patients constitute an at-risk group requiring tailored treatment, including vaccination. The effect of TCZ exposure on the reduction of severe outcomes was not proved here.