A copper(II) tetrapyrazole-based complex of the composition of [Cu(tpyr)(H2O)(ONO2)]NO3 (1), where tpyr represents a tetradentate N-donor ligand formed by the condensation of 1H-pyrazole-5-carbaldehyde in NaOH/MeOH medium, has been prepared and characterized by elemental analysis, infrared spectroscopy, ultraviolet-visible spectroscopy, mass spectrometry, electron paramagnetic resonance and single-crystal X-ray diffraction. Spectrophotometric measurements demonstrated a remarkable peroxidase activity of the complex, which utilized hydrogen peroxide for the oxidation of phenolic compounds such as guaiacol or 3,5-dichloro-2-hydroxybenzene sulfonic acid. The optimum conditions for this reaction were found at pH 8 in ammonium bicarbonate buffer, although the activity was low but still detectable at pH 5-6 in ammonium acetate. As a peroxidase mimic, the complex exhibited enzyme-like Michaelis-Menten kinetics, showing a hyperbolic dependence of the reaction rate on hydrogen peroxide concentration. The determined Km and kcat values were 651 μmol·l-1 and 6.7 × 10-4 s-1, respectively, compared to 41 μmol·l-1 and 73 s-1 for horseradish peroxidase. EPR spectroscopy of the reaction mixture revealed no change in the copper (II) oxidation state during catalysis, suggesting that the oxidation of guaiacol may occur simultaneously with the reduction of hydrogen peroxide to water at the copper centre.

• Klíčová slova
• Copper(II), Crystal structure, MALDI-TOF, Peroxidase activity, Tetrapyrazole, XPS,
• MeSH
• biomimetické materiály * chemie   MeSH
• kinetika MeSH
• komplexní sloučeniny * chemie   chemická syntéza   MeSH
• krystalografie rentgenová MeSH
• měď * chemie   MeSH
• oxidace-redukce MeSH
• peroxid vodíku chemie   MeSH
• peroxidasa * chemie   MeSH
• pyrazoly * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• komplexní sloučeniny * MeSH
• měď * MeSH
• peroxid vodíku MeSH
• peroxidasa * MeSH
• pyrazoly * MeSH

OBJECTIVE: Despite availability of an array of antihypertensive drugs, malignant hypertension remains a life-threatening condition, and new therapeutic strategies for the treatment of malignant hypertension and malignant hypertension-associated organ damage are needed. The aim of the present study was to assess the effects of nitric oxide (NO)-independent soluble guanylyl cyclase (sGC) stimulator on the course of malignant hypertension. The second aim was to investigate if the treatment with sodium-glucose cotransporter type 2 (SGLT2) inhibitor would augment the expected beneficial actions of the sGC stimulation on the course of malignant hypertension. METHODS: As a model of malignant hypertension, Ren-2 transgenic rats (TGR) treated with nonspecific NO synthase inhibitor (Nω-nitro- l -arginine methyl ester, l -NAME) was used. Blood pressure (BP) was monitored by radiotelemetry, and the treatment was started 3 days before administration of l -NAME. RESULTS: The treatment with sGC stimulator BAY 41-8543, alone or combined with SGLT2 inhibitor empagliflozin, abolished malignant hypertension-related mortality in TGR receiving l -NAME. These two treatment regimens also prevented BP increases after l -NAME administration in TGR, and even decreased BP below values observed in control TGR, and prevented cardiac dysfunction and malignant hypertension-related morbidity. The treatment with the SGLT2 inhibitor empagliflozin did not further augment the beneficial actions of sGC stimulator on the course of malignant hypertension-related mortality. CONCLUSION: The treatment with NO-independent sGC stimulator displayed marked protective actions on the course of malignant hypertension-related mortality and malignant hypertension-related cardiac damage. This suggests that application of sGC stimulator could be a promising therapeutic means for the treatment of malignant hypertension.

• Klíčová slova
• malignant hypertension, renin–angiotensin system, sodium-glucose cotransporter type 2 inhibitor, soluble guanylyl cyclase stimulator,
• MeSH
• benzhydrylové sloučeniny farmakologie   MeSH
• glifloziny MeSH
• glukosidy farmakologie   terapeutické užití   MeSH
• hypertenze maligní * prevence a kontrola   farmakoterapie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu Rattus MeSH
• morfoliny MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• potkani transgenní MeSH
• pyrazoly * farmakologie   terapeutické užití   MeSH
• pyrimidiny * terapeutické užití   farmakologie   MeSH
• rozpustná guanylátcyklasa * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BAY 41-8543 MeSH Prohlížeč
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny MeSH
• glukosidy MeSH
• morfoliny MeSH
• NG-nitroargininmethylester MeSH
• pyrazoly * MeSH
• pyrimidiny * MeSH
• rozpustná guanylátcyklasa * MeSH

BACKGROUND: The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting. METHODS: Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests. RESULTS: A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS. CONCLUSIONS: In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.

• Klíčová slova
• ARON-1 study, Axitinib plus pembrolizumab, Cabozantinib plus nivolumab, Immune-oncology combinations,
• MeSH
• anilidy * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• axitinib * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• karcinom z renálních buněk * farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   patologie   mortalita   MeSH
• nivolumab * terapeutické užití   farmakologie   aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři 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
• srovnávací studie MeSH
• Názvy látek
• anilidy * MeSH
• axitinib * MeSH
• cabozantinib MeSH Prohlížeč
• humanizované monoklonální protilátky * MeSH
• nivolumab * MeSH
• pembrolizumab MeSH Prohlížeč
• pyridiny MeSH

Patients with cardioembolic ischemic stroke are commonly prescribed direct oral anticoagulants (DOACs), such as dabigatran (a direct thrombin inhibitor) and factor Xa inhibitors (e.g., apixaban and rivaroxaban), or warfarin to reduce the risk of recurrent stroke. A major concern in anticoagulant therapy is the risk of intracerebral hemorrhage, which is associated with a high mortality rate. Cerebral microbleeds (MBs), small asymptomatic brain hemorrhages detectable by susceptibility-weighted imaging (SWI) on magnetic resonance imaging (MRI), are associated with increased hemorrhagic stroke risk. This study evaluated the incidence of new MBs during 1 year of anticoagulation therapy in patients after cardioembolic stroke. Patients indicated for anticoagulant therapy after cardioembolic stroke and monitored in the cerebrovascular outpatient clinic of our department underwent brain MRI at baseline and after 1 year of therapy. The occurrence of new MBs was assessed using SWI sequences. MBs were categorized based on location into 3 groups: deep (dMBs), lobar (lMBs), and infratentorial (iMBs). A total of 79 patients were included, 53 of whom were male (67.1%), with a median age of 71 years (IQR: 64-76). The majority of patients (n = 50, 63.3%) were treated with apixaban, 16 patients (20.3%) with dabigatran, and 13 patients (16.5%) with warfarin. Baseline MRI revealed MBs in 17 patients (21.5%), including dMBs in 2, lMBs in 16, and iMBs in 2 patients. Follow-up MRI showed new MBs in 8 patients (10.1%), with new dMBs in 1, lMBs in 5, and iMBs in 4 patients. No statistically significant differences were observed in MBs the incidence of new MBs between anticoagulant groups (P = .912). Over 1 year of anticoagulant therapy, new MBs were detected in 10.1% of patients, predominantly in lobar and infratentorial regions. No differences in the incidence of new MBs were identified between the different anticoagulant groups.

• Klíčová slova
• anticoagulation, microbleeds, stroke,
• MeSH
• antikoagulancia * škodlivé účinky   terapeutické užití   MeSH
• cerebrální krvácení * chemicky indukované   diagnostické zobrazování   epidemiologie   MeSH
• cévní mozková příhoda * prevence a kontrola   MeSH
• dabigatran škodlivé účinky   terapeutické užití   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• pyrazoly škodlivé účinky   terapeutické užití   MeSH
• pyridony škodlivé účinky   terapeutické užití   MeSH
• sekundární prevence * metody   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antikoagulancia * MeSH
• apixaban MeSH Prohlížeč
• dabigatran MeSH
• pyrazoly MeSH
• pyridony MeSH

PDGFRA is crucial to tumorigenesis and frequently genomically altered in high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detect PDGFRA mutations and/or amplifications in 15% of cases, suggesting PDGFRA as a therapeutic target. We reveal that the PDGFRA/KIT inhibitor avapritinib shows (1) selectivity for PDGFRA inhibition, (2) distinct patterns of subcellular effects, (3) in vitro and in vivo activity in patient-derived HGG models, and (4) effective blood-brain barrier penetration in mice and humans. Furthermore, we report preliminary clinical real-world experience using avapritinib in pediatric and young adult patients with predominantly recurrent/refractory PDGFRA-altered HGG (n = 8). Our early data demonstrate that avapritinib is well tolerated and results in radiographic response in 3/7 cases, suggesting a potential role for avapritinib in the treatment of HGG with specific PDGFRA alterations. Overall, these translational results underscore the therapeutic potential of PDGFRA inhibition with avapritinib in HGG.

• Klíčová slova
• PDGFRA alteration, PDGFRA amplification, PDGFRA inhibitor, PDGFRA mutation, avapritinib, brain penetrance, diffuse midline glioma, glioblastoma, high-grade glioma, tyrosine kinase inhibitor,
• MeSH
• dítě MeSH
• dospělí MeSH
• gliom * farmakoterapie   genetika   patologie   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• inhibitory proteinkinas * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory mozku * farmakoterapie   genetika   patologie   MeSH
• předškolní dítě MeSH
• protinádorové látky * farmakologie   terapeutické užití   MeSH
• pyrazoly * farmakologie   terapeutické užití   MeSH
• pyrroly MeSH
• růstový faktor odvozený z trombocytů - receptor alfa * genetika   antagonisté a inhibitory   metabolismus   MeSH
• stupeň nádoru MeSH
• triaziny MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• avapritinib MeSH Prohlížeč
• inhibitory proteinkinas * MeSH
• protinádorové látky * MeSH
• pyrazoly * MeSH
• pyrroly MeSH
• růstový faktor odvozený z trombocytů - receptor alfa * MeSH
• triaziny MeSH

Heart failure (HF) is a leading cause of morbidity and mortality, often driven by prolonged exposure to pathological stimuli such as pressure and volume overload. These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren-2 transgenic (TGR) rats and a volume-overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41-8543 (3 mg/kg/day) for 30 weeks, while normotensive Hannover Sprague-Dawley rats served as controls. At the study endpoint (40 weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP-2, TGF-β, and SMAD2/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR-ACF rats receiving sGC stimulators. Notably, all untreated TGR-ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.

• Klíčová slova
• heart failure with reduced ejection fraction, reactive oxygen/nitrogen species, renin‐angiotensin system, soluble guanylate cyclase stimulator,
• MeSH
• agonisté guanylátcyklasy * farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• morfoliny MeSH
• oxidační stres účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• pyrazoly * farmakologie   terapeutické užití   MeSH
• pyrimidiny * farmakologie   terapeutické užití   MeSH
• remodelace komor účinky léků   MeSH
• rozpustná guanylátcyklasa * metabolismus   MeSH
• srdeční selhání * farmakoterapie   etiologie   patofyziologie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté guanylátcyklasy * MeSH
• BAY 41-8543 MeSH Prohlížeč
• morfoliny MeSH
• pyrazoly * MeSH
• pyrimidiny * MeSH
• rozpustná guanylátcyklasa * MeSH

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-treated patients; median PFS was 44.1 months in BR-treated patients (hazard ratio [HR], 0.29; one-sided P = .0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P = .0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P < .0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.

• MeSH
• bendamustin hydrochlorid * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• chronická lymfatická leukemie * farmakoterapie   genetika   mortalita   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• piperidiny * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• pyrazoly * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• pyrimidiny * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• rituximab * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři 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 III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• bendamustin hydrochlorid * MeSH
• piperidiny * MeSH
• pyrazoly * MeSH
• pyrimidiny * MeSH
• rituximab * MeSH
• zanubrutinib MeSH Prohlížeč

Chronic Kidney Disease (CKD) is associated with heightened risk of thrombosis. Prescription of anticoagulants is key to manage it; however, CKD patients have shown an increased risk of bleeding under anticoagulation therapy compared to non-CKD patients. We hypothesized that the sex could modify the metabolism of indoxyl sulfate (IS), a uremic toxin and Apixaban. Our intoxication model shows that higher doses of IS and apixaban accumulate in the plasma of female mice because of expression differences in efflux transporters and cytochromes in the liver, ileum and kidneys, when compared to males. Furthermore, we found that accumulation of apixaban in females contributes to increased bleeding. Transcriptional analysis of liver samples revealed elevated Sult1a1 but reduced Abcg2 and Cyp3a11 in female mice, while in the kidneys the expression rates of Oat1 and Oat3 were respectively lower and higher than those observed in males, potentially affecting drug clearance. Whole proteomics liver analysis confirmed the previous transcriptional results at the protein level and revealed that sex had a major influence in regulating both coagulation and drug metabolism pathways. Thus, our findings underline the need for inclusive clinical and preclinical trials to accurately reflect sex-specific metabolic variations, and to consider CKD-specific changes to optimize dosing, minimize side effects, and improve patient outcomes.

• MeSH
• antikoagulancia MeSH
• chronická renální insuficience metabolismus   MeSH
• indican * metabolismus   MeSH
• játra metabolismus   MeSH
• ledviny metabolismus   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pyrazoly * metabolismus   farmakokinetika   MeSH
• pyridony * metabolismus   farmakokinetika   MeSH
• sexuální faktory MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikoagulancia MeSH
• apixaban MeSH Prohlížeč
• indican * MeSH
• pyrazoly * MeSH
• pyridony * MeSH

PURPOSE: Tropomyosin receptor kinase (TRK) fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients. EXPERIMENTAL DESIGN: We conducted an international retrospective cohort study of patients with TRK fusion-driven central nervous system tumors. RESULTS: A total of 119 patients were identified. The median age at the time of diagnosis was 4.5 years. The majority were reported to have a histology consistent with a diagnosis of high-grade glioma (HGG; 57.1%) followed by low-grade glioma (LGG; 27.7%). Pediatric patients had a better prognosis, with a median overall survival of 185.5 months compared with 24.8 months in adults (P < 0.0001). Patients with LGG also had a better outcome when compared with HGG (P = 0.0012). The objective response was 68.8% with larotrectinib compared with 38.1% for nontargeted treatment. CONCLUSIONS: Children with LGG had a favorable outcome compared with adult glioma and HGG. TRK inhibitors seem to improve tumor control.

• MeSH
• dítě MeSH
• dospělí MeSH
• fúze genů * MeSH
• fúzní onkogenní proteiny * genetika   MeSH
• gliom * genetika   farmakoterapie   patologie   mortalita   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory centrálního nervového systému * genetika   mortalita   patologie   farmakoterapie   diagnóza   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• pyrazoly terapeutické užití   aplikace a dávkování   MeSH
• pyrimidiny terapeutické užití   aplikace a dávkování   MeSH
• receptor trkA * genetika   MeSH
• receptor trkB genetika   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fúzní onkogenní proteiny * MeSH
• inhibitory proteinkinas MeSH
• larotrectinib MeSH Prohlížeč
• pyrazoly MeSH
• pyrimidiny MeSH
• receptor trkA * MeSH
• receptor trkB MeSH

INTRODUCTION: Alopecia areata is a common autoimmune disease which results in reversible hair loss. Janus kinase inhibitors are prescribed for severe alopecia areata with encouraging results. There are no studies comparing the efficacy and safety of Janus kinase inhibitors to traditional treatment options, such as topical immunomodulators and traditional immunosuppressants. AIMS: To retrospectively compare the efficacy and safety of baricitinib, an approved Janus kinase inhibitor, to other treatments for severe AA during a 6-month treatment period. MATERIALS/METHODS: We included patients with newly presenting, relapsing or treatment-resistant alopecia areata with Severity of Alopecia Tool (SALT) score ≥ 50, for the period between July 2021 and July 2023. Medical histories were reviewed and possible side effects were recorded. Primary endpoints were SALT ≤ 20 and SALT ≤ 10 after 6 months of treatment. RESULTS: Seventy-five patients (53 females) were divided into three groups: topical immunomodulators (51 patients); baricitinib (19 patients); and a group receiving pulsed intramuscular corticosteroids or traditional immunosuppressants (11 patients). Twenty-one patients received more than one treatment options within 2 years. After 6 months, the baricitinib group showed superior efficacy with 32% and 26% of patients achieving SALT ≤ 20 and SALT ≤ 10, compared to 12% and 9% in both other groups. Baricitinib demonstrated better secondary outcomes (50% and 90% reduction from initial SALT scores). All treatments exhibited mild-to-moderate and expected side effects. Weight gain, which had not been reported in clinical trials for alopecia areata, was observed in three baricitinib-treated patients. CONCLUSION: Baricitinib was superior to traditional treatments for severe alopecia areata after 6 months. Weight gain concerned 16% of patients receiving baricitinib.

• Klíčová slova
• JAK inhibitors, alopecia areata, baricitinib, baricitinib efficacy, baricitinib safety,
• MeSH
• alopecia areata * farmakoterapie   diagnóza   MeSH
• azetidiny * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• imunosupresiva * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• inhibitory Janus kinas * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• puriny * škodlivé účinky   aplikace a dávkování   MeSH
• pyrazoly * škodlivé účinky   aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• sulfonamidy * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• azetidiny * MeSH
• baricitinib MeSH Prohlížeč
• imunosupresiva * MeSH
• inhibitory Janus kinas * MeSH
• puriny * MeSH
• pyrazoly * MeSH
• sulfonamidy * MeSH