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.

• MeSH
• alopecia areata * farmakoterapie   MeSH
• azetidiny * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• hormony kůry nadledvin terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• imunologické faktory aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva * škodlivé účinky   terapeutické užití   aplikace a dávkování   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   terapeutické užití   MeSH
• pyrazoly * škodlivé účinky   aplikace a dávkování   terapeutické užití   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

• MeSH
• diferenciální diagnóza MeSH
• hormony kůry nadledvin aplikace a dávkování   MeSH
• imunosupresiva aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci choroidey komplikace   MeSH
• odchlípení sítnice komplikace   MeSH
• progrese nemoci MeSH
• pseudotumor orbity * diagnostické zobrazování   farmakoterapie   komplikace   patologie   MeSH
• skleritida * diagnostické zobrazování   komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Fingolimod is a first-in-class, orally administered drug indicated for the treatment of relapsing-remitting multiple sclerosis. It acts as an immunomodulator, is classified as a "disease-modifying therapy", and its main mechanism of action is the modulation of sphingosine-1-phosphate receptors. In this prospective pilot study, whole blood concentrations of fingolimod and fingolimod phosphate obtained during routine health care were measured. In this study, we aimed to determine whether therapeutic monitoring of fingolimod and fingolimod phosphate concentrations can help personalise pharmacotherapy for patients with multiple sclerosis. METHOD: The study group consisted of 73 patients treated with oral fingolimod (0.5 mg) once daily. Blood samples were collected between July 2021 and January 2022. The whole blood concentrations of fingolimod and fingolimod phosphate were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The relationship between the measured concentrations and the absolute peripheral blood lymphocyte count was evaluated. RESULTS: Fingolimod concentrations ranged from 0.61 to 6.21 μg/L, and fingolimod phosphate concentrations from 0.48 to 4.28 μg/L. Significantly higher concentrations of the active metabolite, fingolimod phosphate, and a significantly higher fingolimod phosphate/fingolimod concentration ratio were observed in women. The sum of fingolimod and fingolimod phosphate concentrations was significantly higher in the subgroup of patients with a lower absolute peripheral blood lymphocyte count. CONCLUSION: Although all patients were treated with the same dose of fingolimod (0.5 mg orally daily), a 10-fold difference was observed in the achieved whole blood concentrations of fingolimod and fingolimod phosphate. This wide inter-individual variability may lead to potential toxicity or suboptimal concentrations, with the risk of further deterioration in the clinical condition of patients with multiple sclerosis. Therefore, fingolimod is a suitable candidate for therapeutic drug monitoring, including monitoring patient adherence to treatment.

• MeSH
• dospělí MeSH
• fingolimod hydrochlorid * krev   aplikace a dávkování   farmakologie   MeSH
• imunosupresiva * krev   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• monitorování léčiv metody   MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   krev   MeSH
• roztroušená skleróza farmakoterapie   krev   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: ANCA-associated vasculitis (AAV) is a rare, life-threatening disease which may result in serious pulmonary and kidney damage. Cyclophosphamide or rituximab and high-dose glucocorticoids significantly improved patient outcomes, but at the expense of severe complications. Moreover, many patients still relapse and bear a significant burden of both disease- and treatment-related complications. Alternative complement pathway and C5a receptor signaling were demonstrated to play an important role in AAV pathogenesis. Avacopan is selective C5a receptor inhibitor successfully tested in renal AAV as glucocorticoid-sparing agent. AREAS COVERED: Pharmacokinetic/pharmacodynamic properties, clinical efficacy and safety of avacopan, available clinical trials and real-world experience with avacopan. EXPERT OPINION: In the phase 3 trial avacopan was shown to be non-inferior at six and superior at 12 months compared to high-dose glucocorticoids and either cyclophosphamide or rituximab in patients with active AAV. Treatment with avacopan was well tolerated and associated with improved quality of life. In patients with severe renal AAV, renal function improved more in avacopan-treated than in high-dose glucocorticoid-treated patients. Avacopan could thus replace high-dose glucocorticoids to avoid glucocorticoid-related toxicity and to improve long term renal outcome. As avacopan is CYP 3A4 inhibitor and substrate, drug-drug interactions must be considered during the treatment.

• MeSH
• ANCA-asociované vaskulitidy * farmakoterapie   MeSH
• aniliny MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   farmakologie   MeSH
• glukokortikoidy * aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   farmakologie   MeSH
• kombinovaná farmakoterapie MeSH
• kvalita života * MeSH
• kyseliny nipekotinové MeSH
• lidé MeSH
• receptor pro anafylatoxin C5a antagonisté a inhibitory   MeSH
• rituximab škodlivé účinky   aplikace a dávkování   farmakologie   MeSH
• stupeň závažnosti nemoci MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH

Mycophenolate mofetil (MMF) is an immunosuppressant drug approved for prophylaxis of transplant rejection in patients undergoing solid organ transplantation and is further employed in management of various autoimmune disorders. MMF exhibits notable pharmacokinetic inter- and intraindividual variability necessitating tailored therapeutic approaches to achieve optimal therapeutic outcomes while mitigating risks of adverse effects. The objective of this review was to summarize factors that influence the pharmacokinetics of MMF and its active metabolite mycophenolic acid in order to deduce recommendations for personalized treatment strategies. Presumed predictors were analysed in relation to each of the four pharmacokinetic phases, providing tools and targets for MMF dosing optimization amenable to clinical implementation.

• MeSH
• imunosupresiva * farmakokinetika   aplikace a dávkování   MeSH
• individualizovaná medicína MeSH
• kyselina mykofenolová * farmakokinetika   aplikace a dávkování   MeSH
• lidé MeSH
• rejekce štěpu prevence a kontrola   MeSH
• transplantace orgánů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Roztroušená skleróza je nejčastějším získaným chronickým zánětlivým demyelinizačním onemocněním CNS. Do diferenciální diagnostiky roztroušené sklerózy patří akutní diseminovaná encefalomyelitida, jež je monofázickým autoimunitním demyelinizačním onemocněním. Klinicky se akutní diseminovaná encefalomyelitida projevuje encefalopatií a multifokálním postižením. V rozlišení těchto dvou jednotek nám kromě klinického nálezu může pomoci magnetická rezonance a likvorologické vyšetření. Formou kazuistiky popisujeme vzácnou tumoriformní variantu roztroušené sklerózy, která se v úvodu projevila epileptickým záchvatem a encefalopatií.

Multiple sclerosis is the most common acquired chronic inflammatory demyelinating disease of the central nervous system. The diffferential diagnosis of multiple sclerosis includes acute disseminated encephalomyelitis, which is a monophasic autoimmune demyelinating disease. Clinically, acute disseminated encephalomyelitis is manifested by encephalopathy and multifocal involvement. In addition to clinical findings, magnetic resonance imaging and cerebrospinal fluid examination can hepl us to differentiate these two entities. This case report describes a rare variant of tumefactive multiple sclerosis, which was initially presented with epileptic seizure and encephalopathy.

• Klíčová slova
• ofatumumab,
• MeSH
• akutní diseminovaná encefalomyelitida diagnóza   terapie   MeSH
• demyelinizační autoimunitní nemoci CNS MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• roztroušená skleróza * diagnóza   farmakoterapie   MeSH
• záchvaty etiologie   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• chronická kritická ischemie končetin diagnóza   farmakoterapie   MeSH
• hydroxymethylglutaryl-CoA-reduktasy imunologie   škodlivé účinky   MeSH
• imunosupresiva aplikace a dávkování   terapeutické užití   MeSH
• inhibitory agregace trombocytů aplikace a dávkování   terapeutické užití   MeSH
• komorbidita MeSH
• lidé MeSH
• myozitida chemicky indukované   terapie   MeSH
• nemoci svalů * chemicky indukované   terapie   MeSH
• senioři MeSH
• statiny * škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

Although severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid (SARS-CoV-2 mRNA) vaccines are effective in kidney transplant recipients (KTRs), their immune response to vaccination is blunted by immunosuppression. Other tools enhancing vaccination response are therefore needed. Interestingly, aligning vaccine administration with circadian rhythms (chronovaccination) has been shown to boost immune response. However, its applicability in KTRs, whose circadian rhythms are likely disrupted by immunosuppressants, remains unclear. To assess the impact of vaccination timing on seroconversion in the KTRs population, we analyzed data from 553 virus-naïve KTRs who received 2 doses of messenger ribonucleic acid (mRNA) vaccine. Bayesian logistic regression was employed, adjusting for previously identified predictors of seroconversion, including allograft function, maintenance immunosuppressants, or time since transplantation. SARS-CoV-2 immunoglobulin G (IgG) levels were measured with a median of 47 days after the second dose. The results did not reveal a reliable effect of timing of the first dose but did indicate that earlier timing for the second dose brings a notable benefit-every 1-hour delay in the application was associated with a 16% reduction in the odds of seroconversion (OR 0.84, 95% CI 0.71, 0.998). Similar results were obtained from quantile regression modeling IgG levels. In conclusion, morning vaccination is emerging as a promising and easily implementable strategy to enhance vaccine response in KTRs.

• MeSH
• chronické selhání ledvin chirurgie   imunologie   MeSH
• cirkadiánní rytmus imunologie   MeSH
• COVID-19 * prevence a kontrola   imunologie   MeSH
• dospělí MeSH
• humorální imunita * MeSH
• imunoglobulin G krev   imunologie   MeSH
• imunosupresiva aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• příjemce transplantátu MeSH
• protilátky virové * krev   imunologie   MeSH
• rejekce štěpu imunologie   prevence a kontrola   MeSH
• SARS-CoV-2 * imunologie   MeSH
• senioři MeSH
• transplantace ledvin * MeSH
• vakcinace MeSH
• vakcíny proti COVID-19 * imunologie   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti- N -glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models. METHODS: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg. RESULTS: CD3 + T cell depletion <100/mm 3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected. CONCLUSIONS: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.

• MeSH
• antilymfocytární sérum * imunologie   MeSH
• dospělí MeSH
• galaktosyltransferasy MeSH
• imunosupresiva aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocytární deplece metody   MeSH
• prasata MeSH
• rejekce štěpu imunologie   prevence a kontrola   MeSH
• T-lymfocyty imunologie   účinky léků   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH

BACKGROUND: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti- N -glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models. METHODS: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg. RESULTS: CD3 + T cell depletion <100/mm 3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected. CONCLUSIONS: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.

• MeSH
• antilymfocytární sérum * imunologie   MeSH
• dospělí MeSH
• galaktosyltransferasy MeSH
• imunosupresiva aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocytární deplece metody   MeSH
• prasata MeSH
• rejekce štěpu imunologie   prevence a kontrola   MeSH
• T-lymfocyty imunologie   účinky léků   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH