Effectiveness of antimicrobial therapy for community-acquired pneumonia in real clinical practice

Background. Community-acquired pneumonia (CAP) remains one of the most common infectious diseases, occupying an important place in the structure of mortality worldwide.Aim. To evaluate the effectiveness of antimicrobial therapy for community-acquired pneumonia in hospitalized patients in real clinical practice.Materials and methods. A retrospective, observational study was conducted, which included 236 patients hospitalized for community-acquired pneumonia at the Regional Clinical Hospital in Ryazan in 2019. Based on these case histories, an analysis of the effectiveness of the initial empiric antimicrobial therapy was performed.Results. The initial empiric antimicrobial therapy in 73% of cases included administration of ceftriaxone, in 45% of cases – levofloxacin, in 14% of cases – azithromycin. It was found that initial antimicrobial therapy was effective in 58% of patients who did not require replacement for the antibiotic. A need for a change in the treatment regimen was significantly associated with an increase in the length of hospitalization (p < 0.001), heart rate upon admission (p = 0.032), myelocyte count in the complete blood count (p < 0.001), and urea and blood creatinine levels (p = 0.004 and p = 0.044, respectively). The selected antimicrobial therapy regimen was significantly associated with the expected treatment effectiveness (p = 0.039). The choice of levofloxacin in monotherapy or in combination with ceftriaxone was accompanied by a decrease in the relative risk of replacing the antimicrobial, compared with other treatment regimens (odds ratio (OR) = 0.86 (95% confidence interval (CI): 0.55–1.34) and OR = 0.57 (95% CI: 0.37–0.87), respectively).Conclusion. Empiric antimicrobial therapy for community-acquired pneumonia in real clinical practice complies with current recommendations, however, at the same time, its ineffectiveness persists. Respiratory fluoroquinolones are most effective in treating pneumonia in hospitalized patients.

Short-Term Safety and Efficacy of Onasemnogene Abeparvovec in 10 Patients with Spinal Muscular Atrophy: Cohort Study

Background. The efficacy and safety of onasemnogene abeparvovec have been demonstrated in patients with spinal muscular atrophy (SMA) in several clinical and observational studies. Gene replacement therapy results in Russian patients with SMA is not investigated yet.Objective. The aim of the study is to study the safety and efficacy of onasemnogene abeparvovec in children with SMA in real clinical practice.Methods. The study included patients with proximal 5q SMA administered with onasemnogene abeparvovec. Diagnosis was verified by biallelic deletion in the 7th exon of the SMN1 gene. Gene replacement therapy was administered according to the decision of neurologists consensus in case of the absence of antibodies to the adeno-associated serotype 9 virus. The therapy safety was estimated via clinical and laboratory data from the hospital (at least 7 days) and from outpatient departments (at least 60 days). Efficacy was estimated via CHOP INTEND scale and mastering new motor skills ≥ 6 months after therapy onset.Results. Treatment outcomes were studied in 10 SMA patients aged 19 months (15; 21). All patients developed at least one clinical manifestation (hyperthermia, vomiting, lethargy and/or loose stool) associated with drug administration during the first week of follow-up. Increased hepatic transaminases activity and monocytosis was recorded in all patients, thrombocytopenia — in 9, neutropenia — in 5, increased troponin I concentration — in 3. In three cases it was necessary to increase the oral prednisolone dose of to 2 mg/kg, in one case — the dexamethasone pulse therapy dose. The therapy efficacy was monitored ≥ 6 months after therapy onset via the CHOP INTEND scale in 2 patients (scores increased by 32 and 19 points, respectively), and via mastering new motor skills in 8 patients (positive dynamics was noted in 7 cases).Conclusion. The onasemnogene abeparvovec is relatively safe and quite effective for using in real clinical practice

The use of guselkumab in psoriatic arthritis: evidence from real clinical practice

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine and enthesis from the group of spondyloarthritis that develops in patients with psoriasis. Guselkumab is a biologic disease-modifying antirheumatic drug, an inhibitor of interleukin 23, which has been shown to be effective in the treatment of plaque psoriasis and PsA.Objective: to evaluate the effectiveness of guselkumab treatment in PsA patients.Patients and methods. The study included 16 patients with PsA. All patients received 100 mg of guselkumab subcutaneously at weeks 0, 4, 12, 20. Disease activity and treatment efficacy were assessed at weeks 0, 12 and 24 using the DAS28, ASDAS, BASDAI, DAPSA activity indices, the index of the extent and severity of psoriasis PASI.Results and discussion. During treatment, patients with PsA showed a pronounced positive dynamics of the indices of disease activity and an improvement in the skin condition. Before the treatment with guselkumab, the mean value of the DAS28 index was 4.26±0.64, DAPSA – 37.94±9.45, ASDAS – 2.7±0.65, and BASDAI – 5.49±1.39, after 12 weeks of treatment these indicators decreased to 3.03±0.49; 17.06±4.58; 1.64±0.33 and 3.48±0.66, respectively, and after 24 weeks (after the 4th injection) – to 2.32±0.18; 11.31±2.18; 1.22±0.27 and 2.62±0.78, respectively (p<0.05 for all cases). Before treatment, the average PASI index reached 30.99±15.43, after 12 weeks – 4.55±4.82, and after 24 weeks – 1.05±1.46 (p<0.05). During treatment, a significant improvement in the main manifestations of the disease was noted: regression of peripheral arthritis, spondylitis, and skin rashes.The treatment was well tolerated during the 24 weeks of the study, and no serious adverse events were reported.Conclusion. The data from real clinical practice indicate that guselkumab is highly effective and safe in the treatment of PsA.

Efficacy and safety of anti-CGRP(r) monoclonal antibodies in real clinical practice: preliminary analysis after three months of therapy

Monoclonal antibodies inhibiting calcitonin gene related peptide (CGRP) or its receptor have been widely used for migraine prophylactic therapy for the past three years. Evaluation of their efficacy and safety of therapy in real clinical practice is needed.Objective: to evaluate the efficacy and safety of Erenumab, a monoclonal antibody inhibiting the CGRP receptor during three months of therapy.Patients and methods. Sixty-eight patients (58 women and 10 men, mean age 37±10.4 years) with episodic or chronic migraine who were treated with Erenumab were observed. Patients were assessed with MIDAS, WPAI, and HADS scales; the presence of cutaneous allodynia was evaluated with ASC-12 questionnaire. Patients kept a headache diary and marked adverse events during the whole treatment period.Results and discussion. 47 patients (69%) had chronic migraine and 32 (71.9%) had medication overuse headache. In 48 patients (70%) after 3 injections of Erenumab the number of days with migraine decreased by 50% or more. In 7 patients (10%), the reduction in headache days was more than 75%; 20 (29%) did not experience sufficient effect after three months of therapy. Nineteen adverse events were noted in 15 (22%) patients. Severe constipation led to discontinuation of treatment in two patients (3%).Conclusion. The study showed the efficacy and safety of Erenumab for migraine prophylaxis in both patients with episodic and chronic migraine.

EVALUATION OF THE EFFICACY AND SAFETY OF ETANERCEPT USE IN PATIENTS WITH NON-SYSTEMIC JUVENILE ARTHRITIS: 10-YEAR EXPERIENCE OF USE IN A FEDERAL CENTER

TNF-α inhibitors are used in the treatment of non-systemic variants of juvenile idiopathic arthritis (JIA) in case of ineffectiveness or intolerance to methotrexate. Despite 20 years of experience of using of etanercept in pediatric rheumatology, a long-term study of the efficacy and safety of the drug in real clinical practice remains necessary. Objective of the study: to study the efficacy and safety of etanercept for treatment of various non-systemic JIA subtypes in real clinical practice. Materials and methods of research: data from the case histories of 375 patients (242 girls and 133 boys) with articular forms of JIA for 2010–2020 were included in a retrospective, open, uncontrolled, nonrandomized, continuous multicenter cohort study. The age of debut was 6.3 (2.9; 10.7) years. Demographic characteristics, subtypes of arthritis, indicators of laboratory activity of inflammation, and outcomes were estimated: achievement of remission, exacerbation, and switching from etanercept to another genetically engineered biological drug (GEBD) were assessed. Results: remission was recorded in 78.9% on average after 6 months. The factors that determine the likelihood of achieving remission were the absence of previous therapy with GEBD (p=0.001) and compliance with therapy – OR=2.5 (95% CI: 1.3; 4.7), p=0.006. Exacerbations were recorded in 29.5% and were associated with the presence of the HLA B27 antigen – OR=2.6 (95% CI: 1.1; 6.0), p=0.028, antinuclear factor seropositivity (p=0.060). Change of etanercept to another GEBD was made in 17.4% of children and was associated with a failure to achieve remission – OR=7.7 (95% CI: 4.0–14.3), p=0.000001, with previous exacerbations – OR=14,8 (5.3; 41.2), p=0.0000001 and the development of de novo uveitis – OR=2.4 (95% CI: 1.1–5.3), p=0.038. The arthritis subtype and the presence of concomitant methotrexate therapy did not significantly affect treatment outcomes. Conclusion: achievement of remission, compliance with therapy, history of previous therapy with GEBD, exacerbation of JIA and development of de novo uveitis determined the main outcomes of etanercept therapy. The JIA subtype, as well as concomitant therapy with methotrexate, did not significantly affect the outcomes of the disease, which makes it possible to consider etanercept therapy a very effective and safe method of treating JIA as a genetically engineered first-line therapy of any variants of articular forms of JIA, even in monotherapy with ineffectiveness or intolerance to methotrexate.

Target therapy of luminal HER2-negative advanced breast cancer with PIK3CA mutation: combination of alpelisib plus fulvestrant in real clinical practice

Introduction. Сombination of alpelisib plus fulvestrant is approved in patients with hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer (ABC) after progression on hormonotherapy. Efficacy data of alpelisib in heavily pretreated patients with HR+/HER-2-, PIK3CA-mutated advanced breast cancer are limited, only results from phase I trial are available. Here we report our results of alpelisib efficacy in 19 heavily pretreated patients.Object: to evaluate efficacy and safety of combination alpelisib plus fulvestrant in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer in initial and later lines of therapy in real clinical practice.Materials and methods. Combination of alpelisib plus fulvestrant was investigated in 19 patients with HR+/HER2-, PIK3CAmutated ABC, alpelisib at a dose of 300 mg per day plus fulvestrant at a dose of 500 mg i.m. every 28 days and once on day 15. Treatment continued until disease progression or unacceptable toxicity.Results. From February 2021 19 patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer were treated with alpelisib plus fulvestrant. The data cut off is October 2021. Median lines of treatment in advanced disease was five, including 19 (100%) patients received CDK4/6, 14 (74%) – fulvestrant and/or everolimus and 15 (79%) – chemotherapy. 4 (21%) received alpelisib in a second line, 15 (79%) – in subsequent lines. Median progression-free survival was 7 months. The response was evaluated in 18 patients: partial response was achieved in 5 (28%) patients, stable disease – in 9 (50%), disease progression – 4 (22%). The most frequent adverse events were hyperglycemia – 74% (grade 3 – 22%), creatinine increased – 42% and rash – 37% (grade 3 – 22%). Only one patient has discontinued the treatment due to Quincke`s edema.Conclusions. Combination of alpelisib with fulvestrant is an effective option both in initial and later lines of therapy in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer including fulvestrant, CDK4/6 inhibitors and/or everolimus – pretreated patients.