OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.

• MeSH
• adalimumab terapeutické užití   MeSH
• ankylózující spondylitida * farmakoterapie   mortalita   MeSH
• antirevmatika * terapeutické užití   MeSH
• dospělí MeSH
• etanercept * terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• psoriatická artritida * farmakoterapie   mortalita   MeSH
• registrace * MeSH
• revmatoidní artritida * farmakoterapie   mortalita   MeSH
• senioři MeSH
• tendenční skóre * MeSH
• TNF-alfa * antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• adalimumab MeSH
• antirevmatika * MeSH
• etanercept * MeSH
• infliximab MeSH
• monoklonální protilátky MeSH
• TNF-alfa * MeSH

Patients with metastatic urothelial carcinoma (mUC) are typically elderly and often have other comorbidities that require the use of concomitant medications. In our study we evaluated the association of concomitant use of antibiotics (ATBs), proton pump inhibitors (PPIs), corticosteroids, statins, metformin and insulin with patient outcomes and we validated the prognostic role of a concomitant drug score in mUC patients treated with enfortumab vedotin (EV) monotherapy. Data from 436 patients enrolled in the ARON-2EV retrospective study were analyzed according to the concomitant medications used at baseline. Finally, the patients were stratified into three risk groups according to the concomitant drug score based on ATBs, corticosteroids and PPIs. Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Inferior survival outcomes were observed in ATB users compared to non-users (OS: 7.3 months, 95%CI 5.0 - 12.3 vs 13.7 months, 95%CI 12.2 - 47.3, p = 0.001; PFS: 5.1 months 95%CI 3.3 - 17.7 vs 8.3 months, 95%CI 7.1 - 47.3, p = 0.001) and also in corticosteroid users compared to non-users (OS: 8.4 months, 95%CI 6.6 - 10.0 vs 14.2 months, 95%CI 12.7 - 47.3, p < 0.001; PFS: 6.0 months 95%CI 4.6 - 7.9 vs 8.9 months, 95%CI 7.2 - 47.3, p = 0.004). In the Cox multivariate analysis, the concomitant drug score was a significant factor predicting both OS (HR = 1.32 [95% CI 1.03 - 1.68], p = 0.026) and PFS (HR = 1.23 [95% CI 1.01 - 1.51], p = 0.044). Our findings suggest detrimental impact of concomitant use of ATBs and corticosteroids on survival outcomes and the prognostic utility of the concomitant drug score in previously treated mUC patients receiving EV.

• Klíčová slova
• ARON-2EV study, Antibiotics, Concomitant drug score, Concomitant medication, Corticosteroids, Enfortumab vedotin, NCT05290038, Urothelial cancer,
• MeSH
• antibakteriální látky terapeutické užití   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• inhibitory protonové pumpy terapeutické užití   MeSH
• karcinom z přechodných buněk farmakoterapie   sekundární   patologie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky * terapeutické užití   MeSH
• nádory močového měchýře farmakoterapie   patologie   mortalita   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• urologické nádory farmakoterapie   patologie   mortalita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• enfortumab vedotin MeSH Prohlížeč
• hormony kůry nadledvin MeSH
• inhibitory protonové pumpy MeSH
• monoklonální protilátky * MeSH

BACKGROUND: Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody-drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune-checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real-world analysis comparing the effectiveness of EV to chemotherapy in this setting. METHODS: The data were extracted from the medical records of patients treated with EV or chemotherapy following pembrolizumab for recurrent or progressive aUC after platinum-based chemotherapy. Patients were assessed for overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and duration of response (DoR). RESULTS: Our analysis included 247 patients treated with EV (88, 36%) or chemotherapy (159, 64%). Median OS was 9.1 months (95%CI 7.2-10.7) in the overall study population, 13.6 months (95%CI 10.0-31.0) in patients receiving EV and 6.8 months (95%CI 6.0-8.9) in patients receiving chemotherapy (p < 0.001). The OS benefit of EV was not affected by primary tumour site and histology, metastatic sites, type of first platinum-based chemotherapy or response to pembrolizumab. In the EV cohort, the median PFS was significantly longer (8.8 months [95%CI 6.5-17.0] vs. 3.0 months [95%CI 2.6-3.7]) and the ORR was significantly higher (56% vs. 23%) than in the chemotherapy cohort. CONCLUSIONS: The results of our international analysis of real-world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum-based chemotherapy and anti-PD-1 pembrolizumab, regardless of commonly considered prognostic factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05290038.

• Klíčová slova
• ARON‐2 study, NCT05290038, chemotherapy, enfortumab vedotin, pembrolizumab, real‐world data, sequencing, urothelial carcinoma,
• MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   aplikace a dávkování   MeSH
• inhibitory kontrolních bodů terapeutické užití   MeSH
• karcinom z přechodných buněk farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   aplikace a dávkování   MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• urologické nádory farmakoterapie   patologie   mortalita   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• enfortumab vedotin MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• inhibitory kontrolních bodů MeSH
• monoklonální protilátky MeSH
• pembrolizumab MeSH Prohlížeč

OBJECTIVE: Our goal was to assess the efficacy and safety of intravenous (IV) secukinumab for the treatment of adults with active axial spondyloarthritis (axSpA) in INVIGORATE-1. METHODS: INVIGORATE-1 (NCT04156620) was a randomized, double-blind, parallel-group, phase 3 trial in patients with active axSpA (either radiographic or nonradiographic). Patients were randomized one to one to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks) or IV placebo for 16 weeks. After week 16, patients randomized to placebo were switched to IV secukinumab (3 mg/kg every four weeks), and patients randomized to secukinumab continued treatment through week 52. The primary endpoint was the Assessment of SpondyloArthritis International Society (ASAS40) response at week 16. Safety was evaluated through week 60. RESULTS: Among patients initially randomized to IV secukinumab (n = 264) or placebo (n = 262), 86.0% and 88.9% completed the entire 60-week study period, respectively. A higher proportion of patients receiving secukinumab versus placebo met the primary endpoint (ASAS40 response) at week 16 (40.9% vs 22.9%; P < 0.0001). By week 24, patients who switched from placebo to secukinumab at week 16 achieved ASAS40 response rates comparable to those in patients originally randomized to secukinumab. All secondary efficacy endpoints were met at week 16, and responses were sustained through week 52. No new or unexpected safety signals were observed with IV secukinumab. CONCLUSION: IV secukinumab was effective for the treatment of adults with active axSpA over 52 weeks. The safety profile was consistent with that in previous reports on subcutaneous secukinumab.

• MeSH
• antirevmatika aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• axiální spondyloartritida * farmakoterapie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• intravenózní podání MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antirevmatika MeSH
• humanizované monoklonální protilátky * MeSH
• monoklonální protilátky MeSH
• secukinumab MeSH Prohlížeč

We performed retrospective analysis of relapsed/refractory multiple myeloma (RRMM) patients previously exposed to daratumumab treated with ixazomib, lenalidomide, dexamethasone (IRd) regimen in real clinical practice. Our aim was to evaluate efficacy of IRd in these patients and select a subset of patients that would benefit from this treatment the most. In total, we analyzed 43 daratumumab-exposed RRMM patients treated in our center. Minimal response or better was achieved by 53.5% of patients from the cohort. Median progression free survival (PFS) was 4.56 months (95% CI: 2.56, 8.03) and median overall survival (OS) was 28.92 months (95% CI: 5.4, NR). Duration of response (DOR) was evaluable in 28 patients and reached a median of 21.3 months (95% CI: 6.85, NR). Next, we evaluated hazard ratios (HR) for OS and PFS. There was improved OS in patients that were not-triple refractory or worse (HR = 0.39, 95%Cl (0.14; 1.10), p = .07) and in patients, that had less than three previous lines of treatment (LOT) (HR = 0.13, 95%Cl (0.03; 0.6) p = .003). Similar to OS, there was improved PFS in patients, that were not triple-refractory or worse (HR = 0.52, 95%Cl (0.25; 1.10), p = .08). We concluded, that the best survival benefit for RRMM patients pretreated with daratumumab to IRd regimen was observed in patients that were not triple-refractory and had less than three previous lines of treatment (LOT). The DOR in these patients was 21.3 months (95% CI: 6.85, NR).

• Klíčová slova
• daratumumab, ixazomib, relapsed/refractory multiple myeloma,
• MeSH
• chemorezistence * MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• glycin * analogy a deriváty   aplikace a dávkování   terapeutické užití   MeSH
• lenalidomid * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * farmakoterapie   mortalita   MeSH
• monoklonální protilátky * terapeutické užití   aplikace a dávkování   MeSH
• opakovaná terapie MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sloučeniny boru * aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• daratumumab MeSH Prohlížeč
• dexamethason * MeSH
• glycin * MeSH
• ixazomib MeSH Prohlížeč
• lenalidomid * MeSH
• monoklonální protilátky * MeSH
• sloučeniny boru * MeSH

There is no specific treatment for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a disease that is very rare in the pediatric population. We report the case of a 15-year-old boy who presented with mildly reduced kidney function and nephrotic syndrome. Kidney biopsy revealed PGNMID with monoclonal deposits of IgG3 with kappa light chain restriction. Flow cytometry showed a significant CD38 plasma cell population in the peripheral blood in the absence of other signs of hematological malignancy. The patient was treated with a 6-month course of daratumumab, a monoclonal antibody targeting CD38. There was a significant reduction in proteinuria and normalization of kidney function. Based on positive experience with adults, daratumumab should also be studied in children with PGNMID.

• Klíčová slova
• Adolescent, Daratumumab, Proliferative glomerulonephritis with monoclonal IgG deposits, Proteinuria,
• MeSH
• antigeny CD38 imunologie   analýza   MeSH
• biopsie MeSH
• imunoglobulin G * krev   MeSH
• ledviny patologie   imunologie   účinky léků   MeSH
• lidé MeSH
• membranoproliferativní glomerulonefritida * farmakoterapie   imunologie   patologie   MeSH
• mladiství MeSH
• monoklonální protilátky * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antigeny CD38 MeSH
• daratumumab MeSH Prohlížeč
• imunoglobulin G * MeSH
• monoklonální protilátky * MeSH

OBJECTIVES: Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi-centre, Phase 1, single-agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)-modified anti-CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc-gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM. METHODS: This study comprised two parts: Part-A (dose-escalation involving anti-CD38 mAb pre-treated and naïve patients) and Part-B (dose expansion). Primary endpoints were maximum tolerated dose and recommended Phase 2 dose (RP2D). RESULTS: Thirty-seven heavily pre-treated patients were treated in Part A. Part-B (dose-expansion) was not studied. Seven dose-limiting toxicities were reported at DL3, DL5, DL6, and DL7. RP2D was determined to be 5-7·5 mg/kg. Most common treatment-emergent adverse events were infusion-related reactions in 70·3% (26/37) patients. Grade ≥3 thrombocytopenia was reported in 48·6% (18/37). Overall response rate was 70% in anti-CD38 mAb naïve and 4% in anti-CD38 pre-treated patients, with a median progression-free survival of 7·62 (95%CI: 2·858; not calculable) months and 2·79 (95%CI: 1·150; 4·172) months and, respectively. CONCLUSIONS: The efficacy of SAR442085 was promising in anti-CD38 mAb naïve patients but did not extend to the larger cohort of anti-CD38 mAb pre-treated patients. This observation, along with transient high-grade thrombocytopenia, could potentially limit its clinical use.

• Klíčová slova
• Fc‐engineered, anti‐CD38, daratumumab, isatuximab, multiple myeloma, relapsed/refractory,
• MeSH
• antigeny CD38 antagonisté a inhibitory   imunologie   MeSH
• chemorezistence MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• maximální tolerovaná dávka MeSH
• mnohočetný myelom * farmakoterapie   mortalita   MeSH
• monoklonální protilátky aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• recidiva MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• multicentrická studie MeSH
• Názvy látek
• antigeny CD38 MeSH
• humanizované monoklonální protilátky MeSH
• monoklonální protilátky MeSH

BACKGROUND: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy. OBJECTIVE: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2EV study. PATIENTS AND METHODS: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. RESULTS: Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia. CONCLUSIONS: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab.

• MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   farmakologie   MeSH
• karcinom z přechodných buněk farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• monoklonální protilátky * terapeutické užití   farmakologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   farmakologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• urologické nádory farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• avelumab MeSH Prohlížeč
• enfortumab vedotin MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• monoklonální protilátky * MeSH

BACKGROUND: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy. METHODS: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs. III) and receipt of prophylactic cranial irradiation (yes vs. no). Results of the first planned interim analysis of the two primary end points of overall survival and progression-free survival (assessed on the basis of blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1) with durvalumab as compared with placebo (data cutoff date, January 15, 2024) are reported; results in the durvalumab-tremelimumab group remain blinded. RESULTS: A total of 264 patients were assigned to the durvalumab group, 200 to the durvalumab-tremelimumab group, and 266 to the placebo group. Durvalumab therapy led to significantly longer overall survival than placebo (median, 55.9 months [95% confidence interval {CI}, 37.3 to not reached] vs. 33.4 months [95% CI, 25.5 to 39.9]; hazard ratio for death, 0.73; 98.321% CI, 0.54 to 0.98; P = 0.01), as well as to significantly longer progression-free survival (median 16.6 months [95% CI, 10.2 to 28.2] vs. 9.2 months [95% CI, 7.4 to 12.9]; hazard ratio for progression or death, 0.76; 97.195% CI, 0.59 to 0.98; P = 0.02). The incidence of adverse events with a maximum grade of 3 or 4 was 24.4% among patients receiving durvalumab and 24.2% among patients receiving placebo; adverse events led to discontinuation in 16.4% and 10.6% of the patients, respectively, and led to death in 2.7% and 1.9%. Pneumonitis or radiation pneumonitis with a maximum grade of 3 or 4 occurred in 3.1% of the patients in the durvalumab group and in 2.6% of those in the placebo group. CONCLUSIONS: Adjuvant therapy with durvalumab led to significantly longer overall survival and progression-free survival than placebo among patients with limited-stage small-cell lung cancer. (Funded by AstraZeneca; ADRIATIC ClinicalTrials.gov number, NCT03703297.).

• MeSH
• adjuvantní chemoterapie škodlivé účinky   MeSH
• analýza přežití MeSH
• chemoradioterapie * škodlivé účinky   MeSH
• doba přežití bez progrese choroby * MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * terapeutické užití   škodlivé účinky   MeSH
• Kaplanův-Meierův odhad MeSH
• kraniální ozáření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom plic * farmakoterapie   mortalita   MeSH
• monoklonální protilátky * terapeutické užití   škodlivé účinky   MeSH
• nádory plic * farmakoterapie   mortalita   patologie   terapie   MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• durvalumab MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• monoklonální protilátky * MeSH
• protinádorové látky imunologicky aktivní MeSH
• tremelimumab MeSH Prohlížeč

BACKGROUND AND AIMS: It is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH. METHODS: This study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well. RESULTS: Although apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment. CONCLUSION: This study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients.

• Klíčová slova
• ADP receptor, Acetylsalicylic acid, Antiplatelet, Dyslipidemia, Ticagrelor, Vorapaxar,
• MeSH
• agregace trombocytů * účinky léků   MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II * krev   terapie   farmakoterapie   MeSH
• inhibitory agregace trombocytů * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   farmakologie   MeSH
• PCSK9 inhibitory * MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 * imunologie   MeSH
• senioři MeSH
• separace krevních složek * MeSH
• trombocyty účinky léků   metabolismus   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory agregace trombocytů * MeSH
• monoklonální protilátky MeSH
• PCSK9 inhibitory * MeSH
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 * MeSH