Effectiveness and safety of a 26-week taper regimen of glucocorticoid in GCA patients: Results from a prospective cohort study.

OBJECTIVES: To assess the effectiveness and safety of the 26-week tapering regimen of glucocorticoids (GC) used in the GiACTA trial in a prospective cohort of treatment-naive, biopsy-proven GCA patients. METHODS: Patients with a new diagnosis of biopsy-proven GCA enrolled in the GC arm of the START project (molecular stratification of patients with GCA to tailor GC and tocilizumab therapy) were included. All patients were treated with the 26-week taper regimen of GC used in the GiACTA trial. The primary endpoint was the rate of relapse-free remission at week 52. The secondary endpoints were the proportion of patients with incident aortic damage, cumulative GC doses and GC-related adverse events (AE). RESULTS: 22 patients were included between December 2018 and February 2022. At week 52, 10 patients (45 %, 95 % CI 24-68) were in relapse-free remission. After a median (IQR) follow-up of 35 (22-40) months, 7 patients (32 %, 95 % CI 14-55) were in relapse-free remission. 18 patients with baseline large-vessel imaging underwent CT angiography at the end of the follow-up. No patients had evidence of new aortic dilation, significant progression of aortic damage or large vessel stenosis. 15/22 patients (68 %) had at least one relapse during follow-up. No patients developed visual or cerebrovascular manifestations during relapses. 15/22 (68 %) patients had at least one GC-related AE. CONCLUSIONS: A 26 week taper regimen of GC was effective and safe in inducing and maintaining remission in a sizeable proportion of newly diagnosed GCA patients. However, the frequency of GC-related adverse events was high.

Comparing treatment options for large vessel vasculitis.

INTRODUCTION: Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the major forms of large vessel vasculitis (LVV). Glucocorticoids represent the cornerstone of LVV treatment, however, relapses and recurrences frequently occur when they are tapered or stopped, determining a prolonged exposure to glucocorticoids and a subsequent increased risk of glucocorticoid-related side effects. Therefore, conventional and biologic immunosuppressive drugs have been proposed to obtain a glucocorticoid-sparing effect. AREAS COVERED: We searched PubMed® using the keywords 'giant cell arteritis/drug therapy' and 'Takayasu Arteritis/drug therapy' OR 'Takayasu Arteritis/surgery' This review focuses on the management of LVV, based on the current evidence while highlighting the differences in terms of therapeutic management of TAK and GCA. EXPERT OPINION: Conventional disease modifying anti-rheumatic drugs, such as methotrexate or azathioprine, are recommended in association to glucocorticoids for selected GCA and all TAK patients. Two randomized placebo-controlled trials recently demonstrated the efficacy of tocilizumab in reducing relapses and cumulative prednisone dosage in GCA patients with newly diagnosed or relapsing disease. Observational evidence and two small randomized controlled trials support the use of TNF-alpha inhibitors and tocilizumab as glucocorticoid-sparing agents in relapsing TAK, albeit high-quality evidence regarding the management of TAK is still lacking.

VEXAS Syndrome: A Case Series From a Single-Center Cohort of Italian Patients With Vasculitis.

OBJECTIVE: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) from a single-center cohort of Italian patients with vasculitis, using a clinically oriented phenotype-first approach. METHODS: We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment-resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin-activating enzyme E1 (UBA-1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. RESULTS: Seven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA-1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients. CONCLUSION: To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA-associated vasculitis reported herein warrants further investigation.

Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study.

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a transversal challenge. The INVIDIa study.

AIM: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. METHODS: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017. RESULTS: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001. CONCLUSION: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy.