Assuntos
Antirreumáticos , Artrite Reumatoide , Azetidinas , Purinas , Pirazóis , Sulfonamidas , Humanos , Artrite Reumatoide/tratamento farmacológico , Feminino , Purinas/efeitos adversos , Purinas/uso terapêutico , Purinas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Azetidinas/uso terapêutico , Azetidinas/efeitos adversos , Azetidinas/administração & dosagem , Pessoa de Meia-Idade , Adulto , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Masculino , Estudos de Coortes , Adulto Jovem , Adolescente , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Gravidez , Países Escandinavos e Nórdicos/epidemiologia , Sistema de Registros , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/epidemiologia , IdosoAssuntos
Histiocitose Sinusal , Rim , Osteólise , Fibrose Retroperitoneal , Feminino , Humanos , Pessoa de Meia-Idade , Diagnóstico Diferencial , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Osteólise/diagnóstico , Osteólise/tratamento farmacológico , Osteólise/genética , Tomografia Computadorizada por Raios X , Biópsia , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/genética , Histiocitose Sinusal/patologia , MAP Quinase Quinase 1/genética , Mutação , Azetidinas/uso terapêutico , Piperidinas/uso terapêutico , Nefrectomia , Fibrose Retroperitoneal/diagnóstico , Fibrose Retroperitoneal/tratamento farmacológico , Fibrose Retroperitoneal/genéticaRESUMO
Janus Kinase (JAK) inhibitors have emerged as a novel category of medications to treat a variety of immune-mediated conditions. However, limited insight exists regarding the impact of safety concerns on their usage and prescribing practices. Therefore, the objective of this study was to describe the utilization of JAK-inhibitors in Canada, both nationally and within individual provinces. We used data from IQVIA's Compuscript database. We conducted a repeated cross-sectional study of all JAK-inhibitor units dispensed in retail pharmacies (tofacitinib, ruxolitinib, baricitinib, and upadacitinib) within the ten Canadian provinces from July 1, 2016, to June 30, 2022. Throughout Canada, outpatient pharmacies dispensed an estimated total of 26,126,409 JAK-inhibitor units between 2016 and 2022, averaging 9,431 units dispensed per 100,000 population. All provinces had increasing rates of JAK-inhibitor units dispensed over time, whereby between July 2021 to June 2022, New Brunswick exhibited the highest rates (27,696 units per 100,000), and Prince Edward Island demonstrated the lowest rates (10,065 units per 100,000). In this study, utilization of JAK-inhibitors increased in Canada over the study period, evident at both provincial and national levels. Variability in JAK-inhibitor utilization between provinces underscores the necessity for further investigations to ascertain appropriate usage practices. Key Points ⢠From 2016 to 2022, an estimated total of 26,126,409 JAK-inhibitor units were dispensed in retail pharmacies across Canada, with an average rate of 9,431 units dispensed for every 100,000 people in the population. ⢠Tofacitinib was the most dispensed JAK-inhibitor during the entire study period, making up 76% of all units dispensed. Ruxolitinib, upadacitinib, and baricitinib made up 16%, 7.9%, and 1.1% of the JAK-inhibitor units dispensed, respectively. ⢠The variance in provincial adoption of JAK-inhibitors across Canada might be influenced by several factors, including drug coverage availability, disease prevalence, and physician prescribing patterns.
Assuntos
Azetidinas , Inibidores de Janus Quinases , Piperidinas , Padrões de Prática Médica , Purinas , Pirazóis , Pirimidinas , Pirróis , Sulfonamidas , Humanos , Estudos Transversais , Canadá , Padrões de Prática Médica/estatística & dados numéricos , Inibidores de Janus Quinases/uso terapêutico , Sulfonamidas/uso terapêutico , Pirazóis/uso terapêutico , Azetidinas/uso terapêutico , Pirimidinas/uso terapêutico , Piperidinas/uso terapêutico , Purinas/uso terapêutico , Pirróis/uso terapêutico , Nitrilas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Benzamidas/uso terapêuticoRESUMO
Cardiac fibrosis is characterized by the over-proliferation, over-transdifferentiation and over-deposition of extracellular matrix (ECM) of cardiac fibroblasts (CFs). Cardiac sympathetic activation is one of the leading causes of myocardial fibrosis. Meanwhile, cardiac fibrosis is often together with cardiac inflammation, which accelerates fibrosis by mediating inflammatory cytokines secretion. Recently, the Janus kinase/signal transducer and activator of transcription (JAK/STAT3) signaling pathway has been confirmed by its vital role during the progression of cardiac fibrosis. Thus, JAK/STAT3 signaling pathway is thought to be a potential therapeutic target for cardiac fibrosis. Baricitinib (BR), a novel JAK1/2 inhibitor, has been reported excellent effects of anti-fibrosis in multiple fibrotic diseases. However, little is known about whether and how BR ameliorates cardiac fibrosis caused by chronic sympathetic activation. Isoproterenol (ISO), a ß-Adrenergic receptor (ß-AR) nonselective agonist, was used to modulate chronic sympathetic activation in mice. As expected, our results proved that BR ameliorated ISO-induced cardiac dysfunction. Meanwhile, BR attenuated ISO-induced cardiac fibrosis and cardiac inflammation in mice. Moreover, BR also inhibited ISO-induced cardiac fibroblasts activation and macrophages pro-inflammatory secretion. As for mechanism studies, BR reduced ISO-induced cardiac fibroblasts by JAK2/STAT3 and PI3K/Akt signaling, while reduced ISO-induced macrophages pro-inflammatory secretion by JAK1/STAT3 and NF-κB signaling. In summary, BR alleviates cardiac fibrosis and inflammation caused by chronic sympathetic activation. The underlying mechanism involves BR-mediated suppression of JAK1/2/STAT3, PI3K/Akt and NF-κB signaling.
Assuntos
Azetidinas , Fibroblastos , Fibrose , Camundongos Endogâmicos C57BL , Purinas , Pirazóis , Sulfonamidas , Animais , Fibrose/tratamento farmacológico , Azetidinas/farmacologia , Azetidinas/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Masculino , Fibroblastos/efeitos dos fármacos , Purinas/farmacologia , Purinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Camundongos , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Miocárdio/patologia , Isoproterenol , Células Cultivadas , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Inflamação/tratamento farmacológico , Citocinas/metabolismo , Humanos , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
PURPOSE OF REVIEW: To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD. RECENT FINDINGS: Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi's abrocitinib (ABRO), baricitinib (BARI), and upadacitinib (UPA), are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10 years with moderate-to-severe AD. Fortunately, major safety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred. There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.
Assuntos
Dermatite Atópica , Inibidores de Janus Quinases , Humanos , Dermatite Atópica/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/administração & dosagem , Criança , Adolescente , Purinas/uso terapêutico , Administração Oral , Azetidinas/uso terapêutico , Azetidinas/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Pirimidinas/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Resultado do TratamentoRESUMO
Lichen planus is a chronic auto-inflammatory disease that primarily affects mucocutaneous regions. There are many variants of lichen planus including cutaneous, oral, nail, follicular, and erosive forms. Without any disease-specific treatment options, multi-variant lichen planus can be a challenging disease to manage. We present a 61-year-old woman with multivariant lichen planus that was refractory to numerous systemic and topical therapies. Subsequently, her cutaneous and vulvovaginal lesions improved with the use of oral baricitinib and the erosive oral lesions improved with topical ruxolitinib.
Assuntos
Azetidinas , Líquen Plano , Nitrilas , Purinas , Pirazóis , Pirimidinas , Sulfonamidas , Humanos , Feminino , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Nitrilas/uso terapêutico , Pessoa de Meia-Idade , Purinas/uso terapêutico , Purinas/administração & dosagem , Azetidinas/uso terapêutico , Azetidinas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Pirimidinas/uso terapêutico , Pirimidinas/administração & dosagem , Líquen Plano/tratamento farmacológico , Líquen Plano/patologia , Administração OralAssuntos
Anticorpos Monoclonais Humanizados , Azetidinas , Tratamento Farmacológico da COVID-19 , Pirazóis , Respiração Artificial , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Estudos de Coortes , Pirazóis/uso terapêutico , Pessoa de Meia-Idade , Idoso , Azetidinas/uso terapêutico , Azetidinas/administração & dosagem , Purinas/uso terapêutico , Sulfonamidas/uso terapêutico , COVID-19RESUMO
So far, only a small number of medications are effective in progressive multiple sclerosis (MS). The sphingosine-1-phosphate-receptor (S1PR)-1,5 modulator siponimod, licensed for progressive MS, is acting both on peripheral immune cells and in the central nervous system (CNS). So far it remains elusive, whether those effects are related to the neurotrophin brain derived neurotrophic factor (BDNF). We hypothesized that BDNF in immune cells might be a prerequisite to reduce disease activity in experimental autoimmune encephalomyelitis (EAE) and prevent neurotoxicity. MOG35-55 immunized wild type (WT) and BDNF knock-out (BDNFko) mice were treated with siponimod or vehicle and scored daily in a blinded manner. Immune cell phenotyping was performed via flow cytometry. Immune cell infiltration and demyelination of spinal cord were assessed using immunohistochemistry. In vitro, effects on neurotoxicity and mRNA regulation were investigated using dorsal root ganglion cells incubated with EAE splenocyte supernatant. Siponimod led to a dose-dependent reduction of EAE scores in chronic WT EAE. Using a suboptimal dosage of 0.45 µg/day, siponimod reduced clinical signs of EAE independent of BDNF-expression in immune cells in accordance with reduced infiltration and demyelination. Th and Tc cells in secondary lymphoid organs were dose-dependently reduced, paralleled with an increase of regulatory T cells. In vitro, neuronal viability trended towards a deterioration after incubation with EAE supernatant; siponimod showed a slight rescue effect following treatment of WT splenocytes. Neuronal gene expression for CCL2 and CX3CL1 was elevated after incubation with EAE supernatant, which was reversed after siponimod treatment for WT, but not for BNDFko. Apoptosis markers and alternative death pathways were not affected. Siponimod exerts both anti-inflammatory and neuroprotective effects, partially related to BDNF-expression. This might in part explain effectiveness during progression in MS and could be a target for therapy.
Assuntos
Azetidinas , Compostos de Benzil , Fator Neurotrófico Derivado do Encéfalo , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Feminino , Camundongos , Azetidinas/farmacologia , Azetidinas/uso terapêutico , Compostos de Benzil/farmacologia , Compostos de Benzil/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacologia , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologiaRESUMO
PURPOSE: Heterozygous STAT1 Gain-of-Function (GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC) among Inborn Errors of Immunity. Clinically, these mutations manifest as a broad spectrum of immune dysregulation, including autoimmune diseases, vascular disorders, and malignancies. The pathogenic mechanisms of immune dysregulation and its impact on immune cells are not yet fully understood. In treatment, JAK inhibitors have shown therapeutic effectiveness in some patients. METHODS: We analyzed clinical presentations, cellular phenotypes, and functional impacts in five Taiwanese patients with STAT1 GOF. RESULTS: We identified two novel GOF mutations in 5 patients from 2 Taiwanese families, presenting with symptoms of CMC, late-onset rosacea, and autoimmunity. The enhanced phosphorylation and delayed dephosphorylation were displayed by the patients' cells. There are alterations in both innate and adaptive immune cells, including expansion of CD38+HLADR +CD8+ T cells, a skewed activated Tfh cells toward Th1, reduction of memory, marginal zone and anergic B cells, all main functional dendritic cell lineages, and a reduction in classical monocyte. Baricitinib showed therapeutic effectiveness without side effects. CONCLUSION: Our study provides the first comprehensive clinical and molecular characteristics in STAT1 GOF patient in Taiwan and highlights the dysregulated T and B cells subsets which may hinge the autoimmunity in STAT1 GOF patients. It also demonstrated the therapeutic safety and efficacy of baricitinib in pediatric patient. Further research is needed to delineate how the aberrant STAT1 signaling lead to the changes in cellular populations as well as to better link to the clinical manifestations of the disease.
Assuntos
Candidíase Mucocutânea Crônica , Mutação com Ganho de Função , Imunofenotipagem , Pirazóis , Fator de Transcrição STAT1 , Humanos , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Candidíase Mucocutânea Crônica/genética , Candidíase Mucocutânea Crônica/diagnóstico , Candidíase Mucocutânea Crônica/terapia , Masculino , Feminino , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Azetidinas/uso terapêutico , Purinas/uso terapêutico , Criança , Adolescente , Taiwan , AdultoRESUMO
INTRODUCTION: The transition from fingolimod (FIN) to siponimod (SIP) for Multiple Sclerosis (MS) treatment in the occurrence of Secondary Progressive Multiple Sclerosis (SPMS) diagnosis has increasingly attracted considerable interest in the recent literature. METHODS: We evaluated the efficacy and safety of a direct switch from FIN to SIP in nine MS patients who had switched directly from FIN to SIP due to SPMS diagnosis at the Multiple Sclerosis Center of the University Hospital Policlinico of Bari. RESULTS AND CONCLUSION: Real-world results from our cohort demonstrated that the direct switch from FIN to SIP in patients transitioning in SP course is associated with clinical and disability progression stability, with a favorable safety profile.
Assuntos
Compostos de Benzil , Cloridrato de Fingolimode , Esclerose Múltipla Crônica Progressiva , Humanos , Cloridrato de Fingolimode/uso terapêutico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Compostos de Benzil/uso terapêutico , Azetidinas/uso terapêutico , Nortropanos , Imunossupressores/uso terapêutico , Substituição de Medicamentos , Progressão da Doença , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Resultado do TratamentoRESUMO
Covid-19 disease is implicated in increased mortality among immunocompromised patients. The JAK inhibitor, baricitinib (bar), or the IL-6 inhibitor, tocilizumab (toc), demonstrated a survival benefit in patients with severe disease.However, evidence supporting their use in immunocompromised patients with severe Covid-19 is scarce.We aimed to assess clinical outcomes of bar/toc treatment in immunocompromised patients. A multi-center registry of consecutive immunocompromised patients hospitalized due to severe Covid-19 during the Omicron variant dominance period. After excluding patients who did not require high oxygen supply, patients treated with bar/toc were compared to patients treated by standard of care (SOC). Primary outcome was in hospital mortality. Secondary outcomes were 30 and 60 day mortality, super-infection and thromboembolic events. Among an overall 228 immunocompromised patients hospitalized in six Israeli hospitals with severe Covid-19, 112 patients required high oxygen support, of whom 48 (43%) were treated with bar/toc. In-hospital mortality rates were exceptionally high and did not significantly differ between bar/toc and SOC treated patients (62.5% vs. 64.1%, p = 1.0). A logistic regression analysis revealed that advanced age and incomplete vaccination were predictors of in-hospital mortality. Patients treated with bar/toc had no excess of suspected super-infection (62.8% vs. 60.7%, p = 0.84) or thromboembolic events (8.3% vs 3.1%, p = 0.39). In immunocompromised patients with severe Covid-19 and a high oxygen demand, bar/toc therapy was not associated with reduced mortality or with a higher rate of associated complications, compared to SOC. Larger prospective studies should better address efficacy and safety.
Assuntos
Anticorpos Monoclonais Humanizados , Azetidinas , Tratamento Farmacológico da COVID-19 , COVID-19 , Mortalidade Hospitalar , Hospedeiro Imunocomprometido , Purinas , Pirazóis , SARS-CoV-2 , Sulfonamidas , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/terapia , Sulfonamidas/uso terapêutico , Azetidinas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Pirazóis/uso terapêutico , SARS-CoV-2/imunologia , Purinas/uso terapêutico , Resultado do Tratamento , Imunomodulação/efeitos dos fármacos , Idoso de 80 Anos ou maisAssuntos
Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Estudos Prospectivos , China , Feminino , Masculino , Adulto , Resultado do Tratamento , Janus Quinase 1/antagonistas & inibidores , Adolescente , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Índice de Gravidade de Doença , Adulto Jovem , Pirazóis/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Sulfonamidas/uso terapêutico , Pessoa de Meia-Idade , Azetidinas/uso terapêutico , Nitrilas/uso terapêutico , Piperidinas/uso terapêutico , Criança , Compostos Heterocíclicos com 3 Anéis , PurinasAssuntos
Azetidinas , Purinas , Pirazóis , Sulfonamidas , Vitiligo , Humanos , Azetidinas/uso terapêutico , Azetidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Vitiligo/terapia , Vitiligo/tratamento farmacológico , Purinas/administração & dosagem , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Masculino , Feminino , Adulto , Administração Oral , Pessoa de Meia-Idade , Terapia Combinada , FototerapiaRESUMO
Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA.
Assuntos
Alopecia em Áreas , Inibidores de Janus Quinases , Metanálise em Rede , Humanos , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/imunologia , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/administração & dosagem , Resultado do Tratamento , Administração Oral , Purinas/administração & dosagem , Purinas/efeitos adversos , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Azetidinas/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Imunoterapia/métodos , Imunoterapia/efeitos adversos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Ciclopropanos/uso terapêutico , Índice de Gravidade de Doença , PirazóisRESUMO
INTRODUCTION: Epidermolysis Bullosa Pruriginosa (EBP) is a persistent, recurring disease that seriously affects quality of life. Fewer than 100 cases of EBP have been reported to date. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling, and inhibition of this pathway using Janus kinase (JAK) inhibitors might be a useful therapeutic strategy for these diseases. PATIENT CONCERNS: A male patient, 28 years of age, was admitted to our hospital because of recurrent papules, nodules, and intense itching on the trunk and extremities for 12 years. Repeated large and intense itching has seriously affected the patient normal life. DIAGNOSIS: The patient was diagnosed with EBP based on examination results. INTERVENTIONS: Oral baricitinib tablets (2 mg, once a day)â +â Oral desloratadine citrate disodium tablets (8.8 mg, once a day) combined with topical compound flumethasone ointment and Fucidin cream. OUTCOMES: The patient skin rashes had subsided and flattened remarkable, and his itching was markedly relieved. The visual analogue scale (VAS) itching score of the patient gradually declined from 8 to 9 points to 2 to 3 points. CONCLUSION: This study confirms that baricitinib is effective and feasible in treating EBP, especially in remarkable relieving itching, which rendered new ideas for therapeutic approaches for EBP in the future.
Assuntos
Azetidinas , Purinas , Pirazóis , Sulfonamidas , Humanos , Purinas/uso terapêutico , Masculino , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Azetidinas/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Epidermólise Bolhosa Distrófica/tratamento farmacológico , Administração OralRESUMO
BACKGROUND: Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. METHODS: We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. RESULTS: Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). CONCLUSIONS: In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.
Assuntos
Artrite Reumatoide , Azetidinas , Inibidores de Janus Quinases , Piperidinas , Purinas , Pirazóis , Sulfonamidas , Humanos , Artrite Reumatoide/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Azetidinas/uso terapêutico , Azetidinas/efeitos adversos , Estudos Retrospectivos , Idoso , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Purinas/uso terapêutico , Purinas/efeitos adversos , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Triazóis/uso terapêutico , Triazóis/efeitos adversos , Fatores de Risco , Adulto , PiridinasRESUMO
Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.
Assuntos
Azetidinas , Tratamento Farmacológico da COVID-19 , COVID-19 , Quimioterapia Combinada , Unidades de Terapia Intensiva , Metilprednisolona , Purinas , Pirazóis , SARS-CoV-2 , Sulfonamidas , Humanos , Purinas/uso terapêutico , Purinas/administração & dosagem , Masculino , Feminino , Azetidinas/uso terapêutico , Azetidinas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , COVID-19/mortalidade , COVID-19/complicações , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/administração & dosagem , Resultado do Tratamento , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/administração & dosagemRESUMO
Myasthenia gravis (MG) is an autoimmune disease that targets neuromuscular junctions. While immunotherapy remains the cornerstone of treatment, the effects of Janus kinase (JAK) inhibitors on MG remain underexplored. In this report, we describe the case of a 58-year-old woman with ocular myasthenia gravis who received treatment with the JAK inhibitor, baricitinib for alopecia areata. The patient presented with left eyelid ptosis and an inadequate response to steroids and pyridostigmine, along with symptoms of alopecia areata. Following diagnosis, we initiated a treatment regimen consisting of baricitinib for six months. After initiation of baricitinib, we observed a complete resolution of the patient's MG symptoms, accompanied by hair regrowth, even when steroids were tapered and pyridostigmine was discontinued. Furthermore, the titer of the anti-acetylcholine receptor antibody was decreased. This report represents the first reported case of anti-acetylcholine receptor antibody-positive MG that was successfully treated through the inhibition of JAK activity.
Assuntos
Azetidinas , Miastenia Gravis , Purinas , Pirazóis , Sulfonamidas , Humanos , Miastenia Gravis/tratamento farmacológico , Azetidinas/uso terapêutico , Feminino , Pessoa de Meia-Idade , Sulfonamidas/uso terapêutico , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Resultado do Tratamento , Receptores Colinérgicos/imunologiaRESUMO
Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5 months versus 33.5 months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points ⢠An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. ⢠Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. ⢠The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.
Assuntos
Corticosteroides , Artrite Reumatoide , Azetidinas , Herpes Zoster , Inibidores de Janus Quinases , Humanos , Artrite Reumatoide/tratamento farmacológico , Herpes Zoster/induzido quimicamente , Herpes Zoster/prevenção & controle , Herpes Zoster/epidemiologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Fatores de Risco , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Azetidinas/efeitos adversos , Azetidinas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Piperidinas/administração & dosagem , Incidência , Pirazóis/efeitos adversos , Purinas/efeitos adversos , Pirimidinas/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , COVID-19/epidemiologia , Adulto , SARS-CoV-2 , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêuticoRESUMO
BACKGROUND: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. METHODS: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. RESULTS: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner. CONCLUSIONS: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period.