• Keywords
• bempedová kyselina,
• MeSH
• Ezetimibe therapeutic use   MeSH
• Hypolipidemic Agents * administration & dosage   economics   pharmacology   therapeutic use   MeSH
• Cardiovascular Diseases * drug therapy   complications   mortality   prevention & control   MeSH
• Clinical Studies as Topic MeSH
• Drug Therapy, Combination methods   MeSH
• Diabetes Complications MeSH
• Congresses as Topic MeSH
• Blood Glucose drug effects   MeSH
• Cholesterol, LDL blood   drug effects   MeSH
• Humans MeSH
• Heart Disease Risk Factors MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use   MeSH
• Check Tag
• Humans MeSH

• Keywords
• inclisiran,
• MeSH
• Medication Adherence MeSH
• Cholesterol analysis   blood   MeSH
• Dyslipidemias * drug therapy   MeSH
• Ezetimibe pharmacology   therapeutic use   MeSH
• Hypolipidemic Agents * pharmacology   therapeutic use   MeSH
• Ischemic Stroke MeSH
• Drug Therapy, Combination MeSH
• Comorbidity MeSH
• Cholesterol, LDL drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Small Interfering pharmacology   therapeutic use   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology   therapeutic use   MeSH
• Life Style MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• Keywords
• Baricitinib,
• MeSH
• Alopecia Areata drug therapy   immunology   physiopathology   MeSH
• Alopecia * drug therapy   classification   physiopathology   MeSH
• Azetidines pharmacology   therapeutic use   MeSH
• Adrenal Cortex Hormones pharmacology   therapeutic use   MeSH
• 5-alpha Reductase Inhibitors pharmacology   therapeutic use   MeSH
• Lupus Erythematosus, Cutaneous drug therapy   physiopathology   MeSH
• Lichen Planus drug therapy   physiopathology   MeSH
• Humans MeSH
• Purines pharmacology   therapeutic use   MeSH
• Pyrazolones pharmacology   therapeutic use   MeSH
• Pyrazoles pharmacology   therapeutic use   MeSH
• Sulfonamides pharmacology   therapeutic use   MeSH
• Trichotillomania etiology   psychology   MeSH
• Check Tag
• Humans MeSH

Počet pacientov užívajúcich hypolipidemickú liečbu z roka na rok narastá. V celosvetovom meradle najčastejšie predpisovanými hypolipidemikami sú statíny, ktoré sa stali liekmi prvej línie, ako aj základným kameňom kombinovanej hypolipidemickej liečby. Suboptimálna adherencia ku hypolipidemickej liečbe je spojená so suboptimálnou kontrolou lipidového spektra, s nárastom kardiovaskulárnych ochorení a úmrtí, ako aj so zvyšujúcimi sa nákladmi na manažment liečby dyslipidémií a s ňou súvisiacich pridružených ochorení a komplikácií. Najčastejšou príčinou nonadherencie alebo prerušenia hypolipidemickej liečby býva svalová symptomatológia s následnou intoleranciou statínov, pre ktorú máme zadefinované presné postupy. Možnosťou pokračovania liečby je použitie kombinovanej hypolipidemickej liečby s použitím ezetimibu alebo kyseliny bempedoovej, prípadne ich fixných kombinácií. Recentne publikované predšpecifikované analýzy štúdie CLEAR-Outcomes dokázali, že kyselina bempedoová je účinná v redukcii ďalších (nasledujúcich) kardiovaskulárnych príhod, je účinná u pacientov s rôznymi stupňami poruchy tolerancie glukózy, bez zvýšenia rizika rozvoja novovzniknutého diabetes mellitus a môže byť bezpečne a efektívne použitá v kombinácii s ezetimibom u jedincov s intoleranciou statínov.

The number of patients using hypolipidemic treatment is increasing from year to year. On a global scale, the most frequently prescribed hypolipidemic drugs are statins, which have become first-line drugs as well as the cornerstone of combined hypolipidemic therapy. Suboptimal adherence to hypolipidemic treatment is associated with suboptimal control of the lipid spectrum, with an increase in cardiovascular disease and death, as well as with increasing costs for the management of dyslipidemia treatment and associated diseases and complications. The most common cause of non-adherence or interruption of hypolipidemic treatment is muscle symptomatology with subsequent statin intolerance, for which we have defined precise procedures. The possibility of continuing the treatment is the use of combined hypolipidemic treatment with the use of ezetimibe and/or bempedoic acid, or their fixed combinations. Recently published pre-specified analyzes of the CLEAR-Outcomes trial proved that bempedoic acid is effective in reducing further (subsequent) cardiovascular events, is effective in patients with various degrees of impaired glucose tolerance, without increasing the risk of developing new-onset diabetes mellitus and can be safely and effectively used in combination with ezetimibe in individuals with statin intolerance.

• Keywords
• studie CLEAR OUTCOMES, kyselina bempedoová,
• MeSH
• Dyslipidemias * drug therapy   MeSH
• Ezetimibe * administration & dosage   therapeutic use   MeSH
• Cardiovascular Diseases drug therapy   prevention & control   MeSH
• Drug Therapy, Combination MeSH
• Dicarboxylic Acids * administration & dosage   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

• MeSH
• Antirheumatic Agents * therapeutic use   MeSH
• Azetidines * MeSH
• Janus Kinase Inhibitors * therapeutic use   MeSH
• Tumor Necrosis Factor Inhibitors therapeutic use   MeSH
• Humans MeSH
• Purines * MeSH
• Pyrazoles * MeSH
• Arthritis, Rheumatoid * drug therapy   MeSH
• Sulfonamides * MeSH
• Tumor Necrosis Factor-alpha MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

BACKGROUND: Resistance to endocrine therapies in hormone receptor-positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer. METHODS: SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing. FINDINGS: Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n=74), 150 mg (n=73), 300 mg (n=20), or fulvestrant (n=73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16·6 months (IQR 12·9-19·4) for the camizestrant 75 mg group, 16·3 months (12·9-18·3) for the camizestrant 150 mg group, and 14·7 months (12·7-20·1) for the fulvestrant 500 mg group. Median progression-free survival was 7·2 months (90% CI 3·7-10·9) with camizestrant 75 mg, 7·7 months (5·5-12·9) with camizestrant 150 mg, and 3·7 months (2·0-6·0) with fulvestrant. The hazard ratio for camizestrant 75 mg versus fulvestrant was 0·59 (90% CI 0·42-0·82; p=0·017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0·64 (0·46-0·89; p=0·0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred. INTERPRETATION: Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer. FUNDING: AstraZeneca.

• MeSH
• Estrogen Receptor Antagonists administration & dosage   therapeutic use   MeSH
• Administration, Oral MeSH
• Azetidines MeSH
• Adult MeSH
• Fulvestrant * administration & dosage   MeSH
• Antineoplastic Agents, Hormonal administration & dosage   therapeutic use   MeSH
• Isoquinolines MeSH
• Middle Aged MeSH
• Humans MeSH
• Breast Neoplasms * drug therapy   pathology   mortality   MeSH
• Postmenopause * MeSH
• Receptor, ErbB-2 * analysis   metabolism   MeSH
• Receptors, Estrogen * metabolism   analysis   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

• MeSH
• Ezetimibe pharmacology   therapeutic use   MeSH
• Drug Therapy, Combination MeSH
• Cholesterol, LDL * drug effects   MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Heart Disease Risk Factors MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Comment MeSH
• Overall MeSH

Alopecia areata je autoimunitní onemocnění, které způsobuje nezjizvené vypadávání vlasů. Rozsah alopecie se liší od malé skvrnky po úplnou ztrátu vlasů na hlavě a těle, což může mít velký psychosociální dopad na postižené osoby. Dosud používané léčebné metody zahrnovaly nespecifická imunosupresiva, jako jsou kortikosteroidy, cyklosporin a metotrexát, nebo topické imunomodulátory, jako jsou difencypron, dithranol a dibutylester kyseliny skvarové. Nedostatek konzistentních výsledků, nepříznivý profil vedlejších účinků a obtíže s aplikací jsou hlavními problémy těchto léčebných postupů, což omezuje jejich použití. S rostoucími poznatky o patogenezi onemocnění se objevují nové léčebné možnosti s nadějnými výsledky. Cílem tohoto přehledu je shrnout roli, účinnost a bezpečnost moderních metod, které jsou již ve využití nebo jsou předmětem klinických studií u alopecia areata.

Alopecia areata is an autoimmune disease that causes unscarred hair loss. The extent of alopecia varies from small patches to complete loss of hair on the head and body, which can have a major psychosocial impact on the affected person. Treatment methods used so far have included non-specific immunosuppressants such as corticosteroids, cyclosporine and methotrexate, or topical immunomodulators such as diphencypron, dithranol and squaric acid dibutylester. The lack of consistent results, the adverse side-effect profile and the difficulty of application are the main problems of these treatments, which limit their use. With increasing knowledge of the pathogenesis of the disease, new treatment options are emerging with promising results. The aim of this review is to summarize the role, efficacy and safety of modern treatments already in use or under clinical development in alopecia areata.

• Keywords
• baricitinib,
• MeSH
• Alopecia Areata * drug therapy   MeSH
• Azetidines pharmacology   therapeutic use   MeSH
• Biological Therapy methods   MeSH
• Janus Kinase Inhibitors pharmacology   therapeutic use   MeSH
• Humans MeSH
• Purines pharmacology   therapeutic use   MeSH
• Pyrazoles pharmacology   therapeutic use   MeSH
• Sulfonamides pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH

Za poslední dekády se scénář léčby roztroušené sklerózy (RS) radikálně změnil. Rostoucí dostupnost účinné terapie modifikující chorobu (DMT) posunula terapeutické cíle od snížení počtu relapsů a nárůstu invalidity až k absenci známek aktivity onemocnění jak klinických, tak na magnetické rezonanci. Volba terapie je stále složitější a měla by se řídit odpovídajícími znalostmi mechanismu účinku jednotlivých léků, účinností a jejich bezpečnostním profilem. Vzhledem k tomu, že DMT ovlivňují zejména zánětlivou složku nemoci dominující v počátcích RS, časné zahájení léčby je klíčové. Recentní doporučení se kloní k časnému zahájení terapie s vyšší účinností. Využití skupiny modulátorů S1P receptorů jako léků první volby v léčbě RS by tak mohlo vést ke stabilizaci většího počtu pacientů již od počátku nemoci, a tím ke zlepšení jejich dlouhodobé prognózy.

Over the last decades, the scenario of multiple sclerosis (MS) treatment has changed radically. The increasing availability of effective disease-modifying therapies (DMTs) has shifted therapeutic targets from a reduction in relapses and increase in disability to the absence of signs of disease activity both clinically and on MRI. The choice of therapy is increasingly complex and should be guided by adequate knowledge of the mechanism of action of each drug, its efficacy and safety profile. Since DMTs mainly affect the inflammatory component of the disease predominant in early MS, early initiation of treatment is crucial. Recent recommendations lean towards early initiation of therapy with higher efficacy. Thus, the use of the S1P receptor modulator family of drugs as the first choice in the treatment of MS could lead to the stabilization of more patients from the onset of the disease and thus improve their long-term prognosis.

• Keywords
• ozanimod, ponesimod, siponimod,
• MeSH
• Antirheumatic Agents administration & dosage   therapeutic use   MeSH
• Azetidines administration & dosage   therapeutic use   MeSH
• Benzyl Compounds therapeutic use   MeSH
• Fingolimod Hydrochloride administration & dosage   adverse effects   therapeutic use   MeSH
• Inflammatory Bowel Diseases drug therapy   MeSH
• Indans administration & dosage   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Sphingosine 1 Phosphate Receptor Modulators * administration & dosage   adverse effects   therapeutic use   MeSH
• Oxadiazoles therapeutic use   MeSH
• Multiple Sclerosis drug therapy   MeSH
• Thiazoles administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Ezetimibe pharmacology   therapeutic use   MeSH
• Hyperlipoproteinemia Type II * genetics   MeSH
• Cholesterol, LDL genetics   adverse effects   MeSH
• Humans MeSH
• Proprotein Convertase 9 pharmacology   therapeutic use   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology   therapeutic use   MeSH
• Check Tag
• Humans MeSH