Background. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used as pharmacotherapy for type 2 diabetes mellitus and obesity.

Objective. This study aimed to characterize adverse reactions (ARs) and assess the disproportionality of reporting for GLP-1 agonists registered in the Russian Federation using the national pharmacovigilance database.

Materials and methods. We analyzed all reports submitted to the "Pharmacovigilance" database of the Roszdravnadzor Automated Information System between January 1, 2020, and December 31, 2025, concerning the use of dulaglutide, lixisenatide, liraglutide, semaglutide, tirzepatide, and exenatide. Reporting odds ratios (ROR) and proportional reporting ratios
(PRR) were calculated for the most frequent system organ classes of adverse reactions.

Results. A total of 181 reports concerning GLP-1 agonists were submitted to the Roszdravnadzor database, of which 154 were primary reports. The maximum number of reports (n = 101) was associated with semaglutide. Adverse reactions were mainly represented by type B reactions (allergic reactions, including injection site reactions) and type A reactions (gastrointestinal disorders: nausea, vomiting, abdominal pain). Among the seriousness criteria for all GLP-1 agonists, the clinical significance of the event predominated. There was no statistically significant disproportionality in reporting concerning the development of serious ARs, therapeutic ineffectiveness, ARs related to the system organ classes "gastrointestinal disorders" or "immune system disorders", cases of acute pancreatitis, or the frequency of therapy discontinuation due to AR development.

Conclusions. The assessment of the risks of ARs during GLP-1 agonist therapy based on the analysis of the Russian pharmacovigilance database is limited due to the extremely low frequency of reporting. Active monitoring is required for this drug class, in the form of post-authorization safety studies (PASS). A potential tool for this is the establishment of a Russian registry for patients receiving medication for obesity.

In real-world clinical practice, NSAID prescribing is frequently associated with risks of NSAID-induced gastropathy and nephrotoxicity, particularly when the pharmacokinetic profiles of these drugs in elderly patients are overlooked. A retrospective process audit of NSAID prescriptions was conducted from January 1 to October 1, 2025; the analysis included 149 medical records selected via simple random sampling. Deviations were classified in accordance with the Summary of Product Characteristics (SmPC), Order No. 1094n of the Russian Ministry of Health, and clinical audit principles (WHO, NICE). The assessment covered dosing deviations, duration of therapy, correctness of prescribing regimens, drug-drug interactions, and documentation defects. Formal defects were identified in the majority of patients (use of brand names — 83.9 %; omission of concentration — 50.3 %). Clinically significant deviations included undefined pro re nata regimens (22.1 %), excessive duration of therapy (18.1 %), exceeding the daily dose (16.8 %), and potentially hazardous drug-drug interactions (2.0 %); critical violations were recorded in 20.8 % of patients. The high prevalence of identified deviations highlights the need to update local pain management protocols.

Hypopituitarianism is a chronic disease based on insufficient secretion of hormones in the anterior pituitary gland. Clinical manifestations of hypopituitarism are varied, often the lack of tropic hormones does not have pronounced symptoms, but the impairment of the function of the pituitary depends on the severity of the hormone deficiency. The most common causes of primary pituitarism are pituitary adenoma and complications after surgery or radiation therapy to treat pituitary adenoma. In addition to the formation of a pituitary gland, various types of brain injury such as craniocerebral trauma, iatrogenic trauma during surgery or cranial radiation can also cause a pituitary syndrome. Hypopituitarism caused by radiation exposure to the brain is very rare, but cases have been reported in the literature of patients undergoing radiation therapy. Despite the relevance of this problem, the mechanism of development of pathology is not well researched. The patients who encountered iatrogenic hypopituitarism, as a result of long-term dynamic observation allowed to trace the similarity in the consistent development of symptoms, with each case being unique clinical picture.

Gene therapy is one of the most promising areas of modern medicine and requires the development of robust regulatory mechanisms due to the potential irreversibility of interventions and potential long-term risks.

The aim of the study was a comparative analysis of international and national regulations governing the development, clinical use, and post-marketing monitoring of gene therapy drugs.

A systemic analysis of regulations from the European Union (EU), the United States, the United Kingdom, Japan, China, and the Russian Federation was conducted. It was found that in all legal systems examined, gene therapy is permitted exclusively for therapeutic purposes and is limited to interventions in somatic cells, while heritable genetic changes are prohibited or significantly limited. Regulatory models in the EU and the United States provide for accelerated registration procedures with mandatory long-term monitoring and the implementation of risk management plans. In the Russian Federation, gene therapy is regulated within the framework of pharmaceutical legislation, without classifying it as a separate category. These results demonstrate the need for further harmonization of international approaches to gene therapy regulation.

Background. Acute postoperative pain remains a significant clinical challenge despite advances in anaesthesiology. Multimodal analgesia with non-opioid analgesics is the standard of care. Intravenous (IV) ibuprofen and IV paracetamol are widely used, but their comparative efficacy has been insufficiently studied.

Objective. To perform a systematic review and indirect comparison (network meta-analysis) of the efficacy and safety of IV ibuprofen versus IV paracetamol in adult patients with moderate-to-severe acute postoperative pain.

Methods. A systematic search was conducted in PubMed/MEDLINE, Cochrane Central, Google Scholar, Semantic Scholar up to November 2025. Inclusion criteria: randomized controlled trials (RCTs) in adults comparing IV ibuprofen (800 mg q6h) or IV paracetamol (1000 mg q6h) combined with opioids against a control (placebo + opioids). The primary outcome was pain intensity reduction measured by the area under the curve of the visual analogue scale on movement (AUC–VASM) over 6–24 h. Secondary outcomes were opioid consumption, incidence of any adverse events (AEs), and postoperative nausea and vomiting (PONV). Risk of bias was assessed with the RoB 2.0 tool. Pairwise and network meta-analyses were performed using a random-effects model (DerSimonian — Laird). We calculated standardized mean differences (SMD) and risk ratios (RR) with 95 % confidence intervals (CI). Heterogeneity was evaluated with the I² statistic. A frequentist network meta-analysis was used for indirect comparison.

Results. Six RCTs (879 patients) were included: four on ibuprofen (n=726) and two on paracetamol (n=153). The risk of bias was low/unclear for ibuprofen trials and unclear/high for paracetamol trials. Pairwise meta-analysis confirmed the efficacy of both drugs versus placebo: for ibuprofen, SMD = –0.60 (95 % CI –0.78 to –0.42); for paracetamol, SMD = –0.53 (95 % CI –0.85 to –0.20). Network meta-analysis showed a statistically significant advantage of ibuprofen over paracetamol: SMD = –0.60 (95 % CI –0.78 to –0.42) in favour of ibuprofen, corresponding to a moderate effect size. The pooled reduction in AUC–VASM was 25.68 % (95 % CI 12.60–38.76) for ibuprofen and 13.68 % (95 % CI 7.74–19.62) for paracetamol. Opioid-sparing effects were comparable: 23.3 % vs 27.3 %, respectively. The incidence of any AEs and PONV with ibuprofen did not differ from placebo (RR=1.03, 95 % CI 0.96–1.10 and RR=0.94, 95 % CI 0.58–1.53). Safety data for paracetamol were limited.

Conclusion. Intravenous ibuprofen provides a statistically significant and clinically greater analgesic effect than IV paracetamol in the treatment of moderate-to-severe acute postoperative pain, with a comparable safety profile. These findings support the preferential use of IV ibuprofen in multimodal analgesia regimens for patients without contraindications to NSAIDs.

Relevance. Real-world evidence (RWE) can be widely used in cost-effectiveness analysis (CEA) and budget impact analysis (BIA) conducted to justify the inclusion of new medicines in restrictive drug lists. However, researches of RWE use experience in drug assessment in the Russian Federation is currently limited, which makes it necessary to conduct such a research.

Our goal is to analyze of the practice of using RWE in preparation of dossiers, conducting CEA and BIA for drugs proposed for inclusion in the restrictive drug lists in the Russian Federation.

Materials and methods. The practice of using RWE in a drug assessment was studied through a content analysis of 28 proposals for the inclusion of drugs in restrictive lists (vital and essential drugs list, high-cost nosology list) in 2022, published CEA (n=109) and BIA (n=82) which were used for drug inclusion in 2018–2024.

Results. In the dossier, real-world studies were used primarily for descriptive purposes, to characterize the proposed drug, current treatment practice, and the therapeutic area. In published CEAs RWE was most often used to increase the completeness of costs taken into account (34 % of uses), increase the accuracy of cost calculations (24 %), and take effectiveness into account when calculating the cost-effectiveness ratios (19 %). In the BIA RWE was most often used to calculate the target patient population (51 % of evidence uses), increase the accuracy of cost calculations (22 %), and more fully account for costs (18 %). RWE characterized the proposed drug and/or comparator in only 44 % of cases in CEAs and 22 % in BIAs; in the remaining cases, it described patients, characteristics of medical care, or the use of medical interventions after or as a result of the use of the compared medicinal products. The use of RWE from other countries is prevalent in CEAs (62 % of uses) and accounts for a significant share in the BIAs (31 % of uses).

Conclusions. In drug assessment RWE is used for a wide range of purposes and characterizes a wide range of parameters for the drugs under scope, target patient groups, treatment patterns, and the long-term outcomes of using the drug. The identified specific features of the RWE use practice differ from expectations, according to which its use should be focused primarily on the compared drugs and describe their effectiveness and safety. It was shown that RWE most often did not describe compared drugs and did not address their efficacy and safety. The significant share of non-local RWE necessitates
the development of measures aimed at increasing the volume of local RWE.

Introduction. CDK4/6 inhibitors in combination with endocrine therapy (ET) represent the current standard of care for patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2 — ) locally advanced or metastatic breast cancer (LABC, MBC). Evidence of the clinical efficacy of CDK4/6 inhibitors has been obtained from a series of randomized clinical trials (RCTs) as well as from real-world clinical practice (RWCP) studies in various countries.

Objective. The aim of the ICEDORA study was to analyze the clinical and demographic characteristics and treatment patterns of patients with HR+ HER2– LABC and MBC receiving CDK4/6 inhibitors in RWCP in Moscow (Russia).

Materials and methods. ICEDORA is a non-interventional, retrospective study based on the analysis of data from patients who received CDK4/6 inhibitors in Moscow. Clinical characteristics and treatment details were extracted from primary medical documents (outpatient charts and medical histories) for all patients with HR+ HER2– breast cancer who received ribociclib, palbociclib, or abemaciclib from January 2020 to the end of December 2022. Differences between treatment groups were assessed using the log-rank test. Overall survival (OS) was calculated from the time of breast cancer diagnosis to patient death using the Kaplan-Meier method.

Results. A total of 2,051 patients were included in the analysis. Based on the CDK4/6 inhibitor administered, selected based on clinical assessment in routine clinical practice, the overall population was divided into three treatment groups: 58.7 % of patients received palbociclib, 34.7 % received ribociclib, and 6.6 % received abemaciclib. The median age in the overall population and in the ribociclib and palbociclib groups was 58 years; in the abemaciclib group, it was higher (62 years). In 83.5 % of cases, the human epidermal growth factor receptor 2 (Her2/neu) status was negative, and the
groups were homogeneous regarding this parameter. Ki-67 and estrogen receptor (ER) levels were significantly higher in the abemaciclib group. Among all patients (2,051), 42.1 % were diagnosed with de novo MBC (stage IV). The distribution of disease stages was comparable across groups. The groups differed significantly in the number of metastases due to a larger proportion of patients with a single metastasis in the abemaciclib group (31.9 %) compared to the ribociclib (19.0 %) and palbociclib (16.6 %) groups, where more than one metastatic site was more common. Comorbidity was observed in 90 % of patients. Caution is necessary when interpreting the study results due to differences in the baseline characteristics of patients receiving the different drugs.

Conclusion. The ICEDORA study represents one of the most extensive analyses of the clinical and demographic characteristics and treatment patterns of patients with HR+ HER2– LABC receiving CDK4/6 inhibitors in RWCP. The study clearly demonstrated that comparing the effectiveness of ribociclib, palbociclib, and abemaciclib in the RWCP setting is challenging due to differences in patient clinical and demographic characteristics. Larger, multicenter data with balanced cohorts and long-term follow-up are needed.