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.

Disseminated tuberculosis after anti-TNF alpha treatment: Do not blindly trust the IGRA test.

INTRODUCTION: Interferon gamma release assay (IGRA) is used to detect latent tuberculosis prior to biological treatments in the context of suspected inflammatory rheumatism. METHODS: We report the case of a 50-year-old woman with negative IGRA test before adalimumab introduction for presumed axial spondyloarthritis. RESULTS: The worsening of symptoms under treatment led to further investigations and the diagnostic of disseminated tuberculosis (TB) was later established with miliary and multiple bone locations such as spondylitis and sacroilitis. The patient's history revealed past exposure to tuberculosis. This observation illustrates the limitations of IGRA in such situation due to its variable performance for active TB diagnosis. CONCLUSION: Misdiagnosis is frequent in bone tuberculosis due to non-specific signs. We draw the attention to the importance of a global risk assessment prior to the introduction of biological treatment for suspected chronic inflammatory rheumatism and recall the risk factors for false-negative IGRA. An extended treatment course may be necessary after exposure to anti-TNF-alpha.

Individual contribution of grain outer layers and their cell wall structure to the mechanical properties of wheat bran.

The mechanical properties of wheat bran and the contribution of each constitutive tissue on overall bran properties were determined on a hard wheat (cv. Baroudeur) and a soft wheat (cv. Scipion). Manual dissection allowed three different layers to be separated from wheat bran, according to radial and longitudinal grain orientations, which were identified by confocal laser scanning microscopy as outer pericarp, an intermediate strip (comprising inner pericarp, testa, and nucellar tissue), and aleurone layer, respectively. Tissue microstructure and cell wall composition were determined. Submitted to traction tests, whole bran, intermediate, and aleurone layers demonstrated elastoplastic behavior, whereas pericarp exhibited elastic behavior. By longitudinal orientation, pericarp governed 50% bran elasticity (elastic strength and rigidity), whereas, in the opposite orientation, bran elastic properties were mostly influenced by the other tissues. Regardless of test orientation, the linear force required to bran rupture corresponded to the sum of intermediate and aleurone layer strengths. According to radial orientation, the intermediate strip governed bran extensibility, but according to longitudinal orientation, all tissues contributed until bran disruption. Tissues from both wheat cultivars behaved similarly. A structural model of wheat bran layers illustrated the detachment of pericarp from intermediate layer within radial bran strips.