Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages. Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs-in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive. Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.

Background: The novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single spray (MP-AzeFlu) was compared with a first-line intranasal antihistamine spray (AZE) in Russian seasonal allergic rhinitis (SAR) patients. Methods: Moderate-to-severe SAR/rhinoconjunctivitis patients (n = 149; aged 18–65 years) were randomized to receive MP-AzeFlu (137/50 μg AZE/FP per spray) or AZE (137 μg/spray), both as 1 spray/nostril twice daily, in a multicenter, open-label, 14-day, parallel-group trial. The primary outcome was change from baseline in morning and evening reflective total nasal symptom score (rTNSS). Secondary end points included: change from baseline in reflective total ocular symptom score (rTOSS), reflective total of 7 symptom scores (rT7SS), 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score, and EuroQol-5D (EQ-5D) questionnaire score. Results: When compared with AZE-treated patients, those treated with MP-AzeFlu experienced significantly greater reductions in rTNSS (difference: –2.47; 95% confidence interval [CI] –3.65 to –1.30; p < 0.001), rTOSS (difference: –1.62; 95% CI –2.32 to –0.92; p < 0.001), and rT7SS (difference: –4.34; 95% CI –5.98 to –2.70; p < 0.001). Superior relief observed on day 2 with MP-AzeFlu versus AZE was sustained throughout the study. MP-AzeFlu-treated patients experienced a greater improvement in QoL than AZE-treated patients as measured by overall RQLQ score (mean ± SD 2.91 ± 1.08 vs. 2.05 ± 1.15) and EQ-5D score (mean ± SD 87.4 ± 10.3 vs. 83.0 ± 12.8). MP-AzeFlu was well tolerated. Conclusions: MP-AzeFlu was superior to AZE in reducing moderate-to-severe SAR symptoms, providing earlier and more complete symptom relief.

OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to &lt;75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c &lt;7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c &lt;7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

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