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.

Objectives: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. Methods: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. The cumulative GC doses were calculated, and the main GC-related AEs were collected during the follow-up. Results: After a median follow-up duration of 35.6 (2–111) months, the median cumulative GC dose in the 139 patients was 9184 (1770–24,640) mg, and 131 patients (94%) presented at least one GC-related AE. Infections (63%) were the most frequently reported GC-related AE, followed by metabolic events (63%), including weight gain in 51% of them. Cardiovascular and neuropsychiatric events occurred in 51% and 47% of patients, respectively. Osteoporotic fractures, muscular involvement, digestive events, geriatric deterioration, skin fragility, ophthalmologic complications and hypokalaemia were reported in 9 g. Longer GC durations were associated with cataract occurrence (p = 0.01), weight gain (p = 0.03) and all-grade infections (p = 0.048), especially herpes zoster occurrence (p = 0.003). Neuropsychiatric and metabolic events appeared within the first months after GC introduction, whereas herpes zoster recurred, and most cardiovascular AEs emerged after 1 year. Geriatric events, especially osteoporotic fractures, occurred 2 years after GC introduction. Conclusion: This study highlights how frequent GC-related AEs are and the impact of prolonged GC and cumulative doses.

Objective: To assess patients’ self-reported glucocorticoid (GC)-related adverse events (AEs) in a GCA population. Methods: A questionnaire was sent to the 100 patients most recently diagnosed with GCA in a tertiary centre. This questionnaire included open- and close-ended questions on the disease and GC effects. Eight primary AE areas were analysed: cardiovascular, metabolic, muscle, cognitive and psychologic, bone, cutaneous and hairiness, infective and visual complications. Including derivative subitems from preceding areas, a total of 18 GC-related AEs were analysed separately and according to GC duration. Results: Ninety patients were analysed and 89 (99%) reported at least one GC-related AE [median 6 (range 1–11)]. Cognitive and psychological changes, primarily insomnia (72%), affected 90% of patients. Cutaneous changes and muscle loss affected 70% of patients, with frequent impairment of physical autonomy (P = 0.007) associated with this event. Metabolic issues, especially weight gain (40%) and diabetes mellitus (20%), affected 49% of patients. Conversely, vision troubles and bone fractures were mentioned by 42% and 9% of patients, respectively, and more frequently in patients who received GCs for >18 months (P = 0.01 and P = 0.007, respectively). Cardiovascular changes and infections affected 30% and 26% of patients, respectively. Conclusion: This real-life study of GC tolerance assessed using a self-evaluation provides pragmatic and updated data reminding us that GC tolerance remains more noteworthy than ever. This study suggests carefully monitoring GC-related AEs during follow-up and encourages GC-sparing strategies in some patients.

Our aim was to describe the main features of amyloid goiter in adults with amyloidosis secondary to familial Mediterranean fever. Therefore, we analyzed cases from a French cohort of familial Mediterranean fever patients with amyloidosis and from literature review. Forty-two cases were identified: 9 from the French cohort and 33 from literature review. Ninety percent of patients were on hemodialysis for renal amyloidosis before the development of goiter. The goiter grew up rapidly in 88% of cases; 75.6% of patients were euthyroid, 58% displayed dyspnea, and 44.8% dysphagia. Various features were seen on ultrasound, from diffuse to multinodular goiter. When it was performed, fine-needle aspiration biopsy almost always revealed amyloidosis. Thirty-one patients underwent thyroidectomy: to manage compressive symptoms (72%) or rule out malignancy (27%). Histology showed mature adipose tissue in 64% of cases and lymphocytic infiltration in 21.4%. In conclusion, amyloid goiter in familial Mediterranean fever preferentially occurs in patients with end stage renal failure. Fine-needle aspiration biopsy seems to be a sensitive exam for diagnosis, but thyroidectomy remains sometimes necessary to rule out malignancy or release compressive symptoms.

Few comparative data exist on early infections secondary to remission-induction therapy (RIT) with rituximab (RTX) versus cyclophosphamide (CYC) in newly diagnosed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. We compared and analysed the rates and predictors of severe infection in such patients within the first 6 months following RIT. From the Caen University Hospital databases, we included all consecutive adults newly diagnosed with ANCA-positive granulomatosis with polyangiitis or microscopic polyangiitis between January 2006 and December 2019. We compared rates of survival without severe infection and survival without infections of any severity within 6 months of RIT and used a multivariate Cox analysis to identify predictors of infection. We included 145 patients, 27 in the RTX and 118 in the CYC group. Patients in the RTX group more frequently had pneumococcal vaccination (p < 0.01) and creatinine < 150 µmol/L; other characteristics were comparable between the two groups. Overall, 37 severe infections and 65 infections of any severity were recorded. Rates of survival without severe infection were similar in both groups (p = 0.69), but survival without infections of any severity was lower in the RTX group (p = 0.005). In multivariate analysis, risk factors at diagnosis for severe infections included chronic urinary tract disease, dialysis, and absence of trimethoprim–sulfamethoxazole prophylaxis (p < 0.01 each). Within 6 months of RIT, rates of survival without severe infection were similar in newly diagnosed ANCA-positive AAV patients treated with RTX or CYC, but survival rates without infections of any severity appeared to be lower with RTX treatment.