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Abstract Background Molecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of dermatological diseases. These therapies modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. This review aims to provide an updated summary of targeted immune therapies for inflammatory skin diseases, considering their pathophysiology, efficacy, dosage, and safety profiles. Methods The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted on PubMed over the past 10 years, focusing on randomized clinical trials, case reports, and case series related to targeted immune therapies in dermatology. Eligibility criteria were applied, and data were extracted from each study, including citation data, study design, and results. Results We identified 1360 non-duplicate articles with the initial search strategy. Title and abstract review excluded 1150, while a full-text review excluded an additional 50 articles. The review included 143 studies published between 2012 and 2022, highlighting 39 drugs currently under investigation or in use for managing inflammatory skin diseases. Study limitations The heterogeneity of summarized information limits this review. Some recommendations originated from data from clinical trials, while others relied on retrospective analyses and small case series. Recommendations will likely be updated as new results emerge. Conclusion Targeted therapies have revolutionized the treatment of chronic skin diseases, offering new options for patients unresponsive to standard treatments. Paradoxical reactions are rarely observed. Further studies are needed to fully understand the mechanisms and nature of these therapies. Overall, targeted immune therapies in dermatology represent a promising development, significantly improving the quality of life for patients with chronic inflammatory skin diseases.
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Atopic dermatitis (AD) is a complex and heterogeneous skin disease for which achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, aiming to advance our understanding of the diverse molecular profiles implicated. Although traditionally characterized as a TH2-driven disease, extensive research has recently revealed the involvement of TH1, TH17, and TH22 immune pathways as well as the interplay of pivotal immune molecules, such as OX40, OX40 ligand (OX40L), thymic stromal lymphopoietin, and IL-33. This review explores the mechanistic effects of treatments for AD, focusing on mAbs and Janus kinase inhibitors. It describes how these treatments modulate immune pathways and examines their impact on key inflammatory and barrier biomarkers.
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Dermatite Atópica , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Humanos , Citocinas/imunologia , Citocinas/metabolismo , Inibidores de Janus Quinases/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , AnimaisRESUMO
BACKGROUND: Molecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of dermatological diseases. These therapies modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. This review aims to provide an updated summary of targeted immune therapies for inflammatory skin diseases, considering their pathophysiology, efficacy, dosage, and safety profiles. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted on PubMed over the past 10 years, focusing on randomized clinical trials, case reports, and case series related to targeted immune therapies in dermatology. Eligibility criteria were applied, and data were extracted from each study, including citation data, study design, and results. RESULTS: We identified 1360 non-duplicate articles with the initial search strategy. Title and abstract review excluded 1150, while a full-text review excluded an additional 50 articles. The review included 143 studies published between 2012 and 2022, highlighting 39 drugs currently under investigation or in use for managing inflammatory skin diseases. STUDY LIMITATIONS: The heterogeneity of summarized information limits this review. Some recommendations originated from data from clinical trials, while others relied on retrospective analyses and small case series. Recommendations will likely be updated as new results emerge. CONCLUSION: Targeted therapies have revolutionized the treatment of chronic skin diseases, offering new options for patients unresponsive to standard treatments. Paradoxical reactions are rarely observed. Further studies are needed to fully understand the mechanisms and nature of these therapies. Overall, targeted immune therapies in dermatology represent a promising development, significantly improving the quality of life for patients with chronic inflammatory skin diseases.
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Terapia de Alvo Molecular , Dermatopatias , Humanos , Anticorpos Monoclonais/uso terapêutico , Dermatologistas , Inibidores de Janus Quinases/uso terapêutico , Dermatopatias/tratamento farmacológicoRESUMO
Inborn errors of immunity (IEI) or primary immune deficiencies (PIDD) are caused by variants in genes encoding for molecules that are relevant to the innate or adaptive immune response. To date, defects in more than 450 different genes have been identified as causes of IEI, causing a constellation of heterogeneous clinical manifestations ranging from increased susceptibility to infection, to autoimmunity or autoinflammation. IEI that are mainly characterized by autoinflammation are broadly classified according to the inflammatory pathway that they predominantly perturb. Among autoinflammatory IEI are those characterized by the transcriptional upregulation of type I interferon genes and are referred to as interferonopathies. Within the spectrum of interferonopathies, genetic defects that affect the proteasome have been described to cause autoinflammatory disease and represent a growing area of investigation. This review is focused on describing the clinical, genetic, and molecular aspects of IEI associated with mutations that affect the proteasome and how the study of these diseases has contributed to delineate therapeutic interventions.
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Autoimunidade , Complexo de Endopeptidases do Proteassoma , Humanos , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Autoimunidade/genética , Mutação/genética , SíndromeRESUMO
OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.
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Antimaláricos , Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/efeitos adversos , Antimaláricos/efeitos adversos , Estudos de Coortes , Artrite Reumatoide/epidemiologia , Antirreumáticos/efeitos adversos , Produtos Biológicos/uso terapêuticoRESUMO
Difficult-to-treat Rheumatoid Arthritis (RA-D2T) is a condition in which patients do not achieve the treatment target despite multiple advanced therapies, more others features. Aims: to estimate the frequency of RA-D2T in a cohort comprehensively evaluated (clinical, serology, imaging), and to analyze the associated characteristics. In a second part, the frequency of RA-D2T after 1 year of follow-up, analyzing the predictive variables at baseline and therapeutic behavior. Cross-sectional and prospective study, consecutive RA were included, then those who completed the one-year follow-up were evaluated. RA-D2T frequency was estimated (DAS28-CDAI-SDAI-Ultrasonography (US)-HAQ) at baseline and 1 year. The variables associated and those baseline predictive characteristics of D2T at 1 year, and their independent association by logistic regression were analyzed. The treatment approach was described. Two hundred seventy-six patients completed the evaluation, frequency of RA-D2T (all scores): 27.5%. Anemia, RF high titers and higher HAQ score were independent associated. At year, 125 competed follow-up. RA-D2T (all scores): 33%, D2T-US and D2T-HAQ were 14 and 18.4% (p 0.001). Predictive baseline characteristics D2T (all score): ACPA + (OR: 13.7) and X-ray erosion (OR: 2.9). D2T-US: X-ray erosion (OR: 19.7). Conventional DMARDs, corticosteroids and TNF-blockers were the drugs most used by D2T patients, Jaki were the most used in the switch. We showed different frequencies of RA-D2T according to different objective parameters (scores, images) and their association with patient characteristics. In turn, predictive variables (erosions-ACPA) for RA-D2T at 1 year were analyzed. It was shown that the Jaki were the most used drug in these patients.
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Antirreumáticos , Artrite Reumatoide , Humanos , Estudos Prospectivos , Estudos Transversais , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Corticosteroides/uso terapêutico , Índice de Gravidade de DoençaRESUMO
With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.
Con el avance de los conocimientos en relación con la fisiopatogenia de la dermatitis atópica (DA) se han desarrollado varias formas terapéuticas nuevas. Asimismo, existen nuevos lineamientos para el autocuidado. Por otro lado, aún existe un subdiagnóstico de la DA en México. Así, se vio la necesidad de desarrollar una guía nacional, con base amplia entre las diferentes agrupaciones médicos que atienden pacientes con DA. Se desarrolló la Guía de DA para México (GUIDAMEX) con la metodología ADAPTE, con el aval y la participación de diez sociedades médicas nacionales, desde médicos del primer contacto hasta alergólogos y dermatólogos. A lo largo del escrito se contestan preguntas clínicas clave que llevan a recomendaciones y sugerencias para el diagnóstico de la DA (incluyendo diagnóstico diferencial con síndromes de inmunodeficiencia), el reconocer de las comorbilidades y complicaciones, las medidas generales (tratamiento no farmacológico) incluyendo la educación terapéutica, el tratamiento de los brotes y el tratamiento de mantenimiento. Este último abarca las medidas generales de evitar agravantes, el tratamiento de primera línea reparador de la barrera cutánea, de segunda línea (manejo proactivo tópico), hasta la fototerapia y el tratamiento sistémico de la tercera línea, incluyendo dupilumab y los inhibidores de la cinasa de Jano.
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Dermatite Atópica , Humanos , Dermatite Atópica/terapia , Dermatite Atópica/tratamento farmacológico , México , Comorbidade , Diagnóstico Diferencial , Fototerapia/métodosRESUMO
OBJECTIVES: Evaluate the importance of treatment sequencing in SELECT-COMPARE, assessing potential differences between starting upadacitinib or adalimumab therapy following inadequate MTX response. METHODS: Patients from SELECT-COMPARE were randomized to upadacitinib 15 mg once daily, placebo or adalimumab 40 mg. Per protocol, patients with <20% improvement in tender or swollen joint counts (weeks 14, 18, 22) or failure to achieve Clinical Disease Activity Index (CDAI) low disease activity (LDA) at week 26 were blindly switched from upadacitinib to adalimumab or vice versa. Treatment outcomes, including clinical remission/LDA, physical function, pain and a novel combined endpoint for deep response, were evaluated through 48 weeks and corresponding time-averaged response rates determined. Data were analysed by initial randomized group regardless of any subsequent switch in therapy. RESULTS: This post hoc analysis included 651 patients initially randomized to upadacitinib (of whom 252 switched to adalimumab) and 327 patients initially randomized to adalimumab (of whom 159 switched to upadacitinib). At week 48, patients randomized to either therapy demonstrated similar achievement of most treatment endpoints. Greater improvements in the total time spent in a lower disease state were observed for initial upadacitinib vs initial adalimumab therapy across most clinical and patient-reported outcomes through 48 weeks, and the median time to DAS28(CRP) <2.6/≤3.2 occurred 6-8 weeks earlier among those randomized to upadacitinib. CONCLUSION: Following a modified treat-to-target strategy, rates of CDAI remission/LDA and DAS28(CRP) <2.6/≤3.2 at 48 weeks were similar, regardless of starting therapy. However, patients initially receiving upadacitinib reached treatment targets more quickly and spent more time in clinical targets over the initial 48 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02629159.
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Antirreumáticos , Artrite Reumatoide , Humanos , Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Objetivos , Método Duplo-Cego , Artrite Reumatoide/tratamento farmacológico , Resultado do Tratamento , Quimioterapia CombinadaRESUMO
Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.
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A dermatite atópica (DA) é uma doença cutânea inflamatória, crônica, comum, complexa e de etiologia multifatorial, que se manifesta clinicamente com prurido muitas vezes incapacitante, lesões recorrentes do tipo eczema, xerose e que pode evoluir para liquenificação. Embora o conhecimento sobre a sua fisiopatologia venham crescendo nos últimos anos, ainda as formas graves são frequentes e representam um desafio para o clínico. Para o presente guia realizou-se revisão não sistemática da literatura relacionada à DA grave refratária aos tratamentos habituais com o objetivo de elaborar um documento prático e que auxilie na compreensão dos mecanismos envolvidos na DA, assim como dos possíveis fatores de risco associados à sua apresentação. A integridade da barreira cutânea é um dos pontos fundamentais para a manutenção da homeostase da pele. Além dos cuidados gerais: evitação dos agentes desencadeantes e/ou irritantes, o uso de hidratantes, suporte emocional, entre outros, o uso de agentes anti-inflamatórios/imunossupressores de uso tópico e/ou sistêmico também foi revisado. A aquisição de novos agentes, os imunobiológicos e as pequenas moléculas, melhorou a terapêutica para os pacientes com formas graves de DA, sobretudo as refratárias aos tratamentos convencionais.
Atopic dermatitis is a chronic, common, and complex inflammatory skin disease with a multifactorial etiology. It manifests clinically with often disabling pruritus, recurrent eczema-like lesions, and xerosis, and can progress to lichenification. Although understanding of the disease's pathophysiology has been growing in recent years, severe forms are still frequent and represent a challenge for clinicians. A non-systematic review of the literature on severe atopic dermatitis refractory to conventional treatment was conducted to develop the present guide, whose purpose is to help clarify the mechanisms involved in the disease and possible risk factors. The integrity of the skin barrier is fundamental for maintaining skin homeostasis. In addition to general care, patients should avoid triggering and/or irritating agents and moisturizers and seek emotional support, etc.; the use of topical and/or systemic anti-inflammatory/immunosuppressive agents was also reviewed. New agents, immunobiologicals, and small molecules have led to a broader range of therapies for patients with severe forms of the disease, especially cases refractory to conventional treatment.
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Humanos , Sociedades Médicas , Imunoglobulina E , Ciclosporina , Corticosteroides , Inibidores de Calcineurina , Anticorpos MonoclonaisRESUMO
A dermatite atópica é a doença inflamatória cutânea mais prevalente mundialmente. A via JAK/STAT tem papel importante no mecanismo da doença e as pequenas moléculas inibidores de JAK são fármacos com grande potencial de uso na dermatite atópica. Foi realizada uma revisão sistemática da literatura na base de dados PubMed, utilizando os termos "atopic dermatitis" e/ou "JAK inhibitors" e/ou "small molecules" entre 2017 e 2022. Foram incluídos os resultados disponíveis de estudos de fase 3, avaliando o uso de inibidores de JAK em apresentações tópicas e sistêmicas. Entre 646 estudos, foram selecionados 37 em humanos que avaliaram a eficácia e segurança dos inibidores de JAK. Os resultados do uso, quando bem indicados, mostraram-se positivos e em alguns casos superiores a outros tratamentos já preconizados para o controle da dermatite atópica, com um bom perfil de segurança.
Atopic dermatitis is the most common inflammatory skin disease worldwide. The JAK/STAT pathway plays an important role in the disease mechanism, and small-molecule JAK inhibitors are drugs with great potential for use in atopic dermatitis. We systematically reviewed PubMed using the search terms "atopic dermatitis" AND/OR "JAK inhibitors" AND/OR "small molecules" for studies published between 2017 and 2022. Results from phase III trials evaluating both topical and systemic application of JAK inhibitors were included. Of 646 studies retrieved, 37 evaluating the efficacy and safety of JAK inhibitors in humans were selected for analysis. When properly indicated, the use of JAK inhibitors yielded positive results, some of which were superior to those of recommended treatments for the control of atopic dermatitis, with a good safety profile.
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HumanosRESUMO
OBJECTIVE: One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modifying antirheumatic drugs (cDMARD and/or bDMARD) failed. METHODS: We searched for randomized controlled trials comparing efficacy and safety of jakinibs for RA treatment using the Web of Science, Scopus, PubMed, and clinicaltrials.gov databases with the terms: "rheumatoid arthritis" OR "arthritis rheumatoid" OR "RA" AND "inhibitor" OR "jak inhibitor" AND "clinical trial" OR "treatment" OR "therapy". RESULTS: All jakinibs achieved good results in ACR 20, 50, 70 and with CRP-DAS28 for LDA and remission, upadacitinib showed better results compared to the others. In ESR-DAS28 for remission, tofacitinib achieved the best result. Regarding the safety of all jakinibs, peficitinib, baricitinib and filgotinib did not register deaths in their studies unlike tofacitinib that presented 11 deaths. Despite all benefits of jakinibs, the use in patients with severe liver and kidney disease should be avoided. CONCLUSIONS: Jakinibs in monotherapy or in combination with methotrexate can be considered a viable alternative in the treatment of moderate-to-severe RA. Even after failures with combination of cDMARDS and bDMARDS, jakinibs demonstrated efficacy.
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Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Inibidores de Janus Quinases/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/enzimologia , Azetidinas/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Quimioterapia Combinada , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Inibidores de Janus Quinases/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Metotrexato/administração & dosagem , Piperidinas/administração & dosagem , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Sulfonamidas/administração & dosagem , Resultado do TratamentoRESUMO
Alopecia areata (AA) is a chronic and autoimmune disease frequently characterized by a challenge management between dermatologists. At present, JAK-inhibitors have demonstrated encouraging results in AA treatment. Therefore, this study reports a case of alopecia universalis in a patient with rheumatoid arthritis (RA), whose methotrexate therapy shown unsatisfactory response in RA control. After the introduction of 10 mg (oral route) per day of tofacitinib, a JAK-inhibitor, an improvement of almost 50% in severity alopecia tool score occurred with maintained response even after 3 months of medication suspension. From this time, we corroborate the effectiveness of JAK-inhibitors presented in the scientific literature. In addition, we inquiry the real impact of methotrexate on JAK-start signaling inhibition in AA pathophysiology.
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Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical response as once-daily monotherapy in patients with moderate to severe RA, also in combination with methotrexate (MTX), who had an inadequate response to MTX. The findings from studies of this new JAK inhibitor have shown that, both in monotherapy as well as in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it has efficacy, safety and tolerability in RA patients.
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Adamantano/análogos & derivados , Artrite Reumatoide/tratamento farmacológico , Niacinamida/análogos & derivados , Adamantano/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Janus Quinases/antagonistas & inibidores , Niacinamida/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: The introduction of JAKs inhibitors for the treatment of rheumatoid arthritis represents a promising new era in the management of the disease. New compounds under investigation, like upadacitinib, with greater selectivity for JAK1 inhibition have recently been approved for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs. AREAS COVERED: Herein, the authors review the pharmacological data, the therapeutic efficacy, and safety data of upadacitinib before providing the reader with their critical evaluation and future perspectives. EXPERT OPINION: Upadacitinib was able to accomplish all the primary and secondary end points in most of the trials, with a safety profile that is similar to the other JAK inhibitors. It has also demonstrated superiority over a tumor necrosis factor inhibitor and data on new indications is also favorable. Upadacitinib is a promising new drug for the treatment of rheumatoid arthritis. GLOSSARY: Adalimumab: ADA; American College of Rheumatology: ACR; Assessment of Spondylarthritis International Society 40: ASAS40; Ankylosis Spondylitis: AS; Area under the Curve: AUC; Biological Disease-modifying arthritis drugs: bDMARDs; Clinical disease activity index: CDAI; C Reactive Protein: CRP; Conventional Synthetic Disease-modifying arthritis drugs: csDMARDs; Deep Venous Thrombosis: DVT; Disease arthritis score: DAS.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Artrite Reumatoide/enzimologia , Artrite Reumatoide/imunologia , Proteína C-Reativa/metabolismo , Quimioterapia Combinada , Humanos , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Resultado do TratamentoRESUMO
La Dermatomiositis Juvenil representa el 75-80% de las miopatías inflamatorias juveniles. Si bien, tiene baja incidencia y prevalencia, presenta importante morbilidad dada por sus manifestaciones cutáneas, musculares, pulmonares, gastrointestinales, cardiacas, entre otras. Corresponde a un desorden poligénico con múltiples factores gatillantes, que determina el desarrollo de una vasculopatía que lleva a atrofia muscular, inflamación y activación de vías del IFN-1. Actualmente su diagnóstico se basa en las guias EULAR/ACR (2017). En los últimos años, se han descubiertos distintos subtipos de la enfermedad, basados en el perfil de autoanticuerpos específicos de miositis, lo que ha permitido establecer pronóstico y estrategias terapéuticas personalizadas. El manejo farmacológico continúa basándose principalmente en el uso de corticoesteroides y DMARDs, así como también terapia biológica; en los últimos años, los inhibidores JAK han mostrado resultados promisorios, convirtiéndose en la más nueva alternativa terapéutica para el control de la enfermedad.
Juvenile Dermatomyositis represents 75-80% of juvenile inflammatory myopathies. Although it has a low incidence and prevalence, it presents significant morbidity due to its cutaneous, muscular, pulmonary, gastrointestinal and cardiac manifestations, among others. It corresponds to a polygenic disorder with multiple triggering factors, which determines the development of a vasculopathy that leads to muscle atrophy, inflammation and activation of IFN-1 pathways. Currently its diagnosis is based on the EULAR/ACR guidelines (2017). In recent years, different subtypes of the disease have been discovered, based on the profile of myositis-specific autoantibodies, which has made it possible to establish prognosis and personalized therapeutic strategies. Pharmacological management continues to be based mainly on the use of corticosteroids and DMARDs, as well as biological therapy; In recent years, JAK inhibitors have shown promising results, becoming the newest therapeutic alternative for disease control.
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Humanos , Dermatomiosite/classificação , Dermatomiosite/diagnóstico , Dermatomiosite/terapia , Terapia Biológica , Corticosteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Dermatomiosite/epidemiologia , Inibidores de Janus QuinasesRESUMO
Alopecia areata is a common autoimmune disease, with a negative impact in health-related quality of life, especially when affecting children and adolescents. Current medical therapies, mainly for severe disease, are not effective. There are no FDA (Food and Drug Administration)- or ANVISA (Agência Nacional de Vigilância Sanitária)-approved therapy for children with alopecia areata. JAK inhibitors are emerging as a promising therapy.
RESUMO
Muitas citocinas, incluindo as interleucinas (ILs), os interferons (IFNs) e outras moléculas, utilizam a via de transdução e transcrição Janus-kinase (Janus-kinase/signal transducers activators of transcription JAK-STAT) para a transmissão de sinais da membrana citoplamástica para o núcleo das células. Essas citocinas inflamatórias dependem dessa sinalização JAK-STAT, que é indispensável para a função imune e hematopoiética. Sendo assim, desenvolveram-se inibidores de JAKs para o tratamento de diversas doenças inflamatórias autoimunes e hematológicas em seres humanos. Os inibidores de JAKs têm se mostrado eficazes no tratamento de dermatite atópica, alopecia areata, psoríase e vitiligo em seres humanos. Dentre os inibidores de JAK incluem-se: tofacitinib, ruxolitinib, baricitinib e oclacinitib. O oclacinitib é de uso exclusivo da medicina veterinária, e estudos recentes demonstram que esse fármaco tem um efeito rápido na redução do prurido e nas lesões de cães com dermatite atópica. Este trabalho teve como objetivo revisar essa nova e promissora classe de medicamentos, com foco no oclacinitib usado na medicina veterinária.(AU)
The Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway is utilized by cytokines, including interleukins, interferons (IFNs), and other molecules to transmit signals from the cell membrane to the nucleus. Inflammatory cytokines rely on JAK-STAT signaling, which is indispensable for immune and hematopoietic function. JAK inhibitors were developed for the treatment of a variety of inflammatory, immune-mediated, and hematopoietic disorders in humans. Evidence suggests that JAK inhibitors are efficacious in the treatment of atopic dermatitis, alopecia areata, psoriasis, and vitiligo. The first generation of JAK inhibitors includes tofacitinib, ruxolitinib, baricitinib, and oclacitinib. Oclacitinib is used exclusively in veterinary medicine, and recent studies have shown that this drug has a rapid effect on pruritus and lesion reduction in dogs with atopic dermatitis. This article aimed to review this new class of drugs, focusing on the use of oclacitinib in veterinary medicine.(AU)
Muchas citocinas, entre ellas las interleucinas (ILs), interferones (IFNs) y otras moléculas utilizan la vía de la transducción y transcripción Janus-quinasa (Janus kinase/signal transducers and activators oftranscription - JAK-STAT) para la transmisión de señales desde la membrana citoplasmática hacia el núcleo celular. Esas citocinas inflamatorias dependen de esa señalización JAK-STAT, indispensable para la función inmune y hematopoyética. En seres humanos, se han desarrollado inhibidores de JAKs para el tratamiento de diferentes tipos de enfermedades inflamatorias autoinmunes y hematológicas. También en humanos, los inhibidores de JAKs se han mostrado eficientes para el tratamiento de dermatitis atópica, alopecia areata, psoriasis y vitíligo. Algunos de estos inhibidores son el tofacitinib, ruxolitinib, baricitinib y el oclacitinib. Esta última droga, oclacitinib, es de uso exclusivo en medicina veterinaria y estudios recientes han demostrado que tiene rápido efecto en la disminución deli prurito y lesiones de perros con dermatitis atópica. Este trabajo tuvo como objetivo revisar la literatura relacionada con esta nueva y prometedora clase de medicamentos, haciendo foco en el oclacitinib utilizado en medicina veterinaria.(AU)
Assuntos
Animais , Janus Quinases/antagonistas & inibidores , Dermatite Atópica/terapia , Dermatite Atópica/veterinária , Interleucinas , Inibidores de Proteínas Quinases/análise , Prurido/veterináriaRESUMO
Muitas citocinas, incluindo as interleucinas (ILs), os interferons (IFNs) e outras moléculas, utilizam a via de transdução e transcrição Janus-kinase (Janus-kinase/signal transducers activators of transcription JAK-STAT) para a transmissão de sinais da membrana citoplamástica para o núcleo das células. Essas citocinas inflamatórias dependem dessa sinalização JAK-STAT, que é indispensável para a função imune e hematopoiética. Sendo assim, desenvolveram-se inibidores de JAKs para o tratamento de diversas doenças inflamatórias autoimunes e hematológicas em seres humanos. Os inibidores de JAKs têm se mostrado eficazes no tratamento de dermatite atópica, alopecia areata, psoríase e vitiligo em seres humanos. Dentre os inibidores de JAK incluem-se: tofacitinib, ruxolitinib, baricitinib e oclacinitib. O oclacinitib é de uso exclusivo da medicina veterinária, e estudos recentes demonstram que esse fármaco tem um efeito rápido na redução do prurido e nas lesões de cães com dermatite atópica. Este trabalho teve como objetivo revisar essa nova e promissora classe de medicamentos, com foco no oclacinitib usado na medicina veterinária.
The Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway is utilized by cytokines, including interleukins, interferons (IFNs), and other molecules to transmit signals from the cell membrane to the nucleus. Inflammatory cytokines rely on JAK-STAT signaling, which is indispensable for immune and hematopoietic function. JAK inhibitors were developed for the treatment of a variety of inflammatory, immune-mediated, and hematopoietic disorders in humans. Evidence suggests that JAK inhibitors are efficacious in the treatment of atopic dermatitis, alopecia areata, psoriasis, and vitiligo. The first generation of JAK inhibitors includes tofacitinib, ruxolitinib, baricitinib, and oclacitinib. Oclacitinib is used exclusively in veterinary medicine, and recent studies have shown that this drug has a rapid effect on pruritus and lesion reduction in dogs with atopic dermatitis. This article aimed to review this new class of drugs, focusing on the use of oclacitinib in veterinary medicine.
Muchas citocinas, entre ellas las interleucinas (ILs), interferones (IFNs) y otras moléculas utilizan la vía de la transducción y transcripción Janus-quinasa (Janus kinase/signal transducers and activators oftranscription - JAK-STAT) para la transmisión de señales desde la membrana citoplasmática hacia el núcleo celular. Esas citocinas inflamatorias dependen de esa señalización JAK-STAT, indispensable para la función inmune y hematopoyética. En seres humanos, se han desarrollado inhibidores de JAKs para el tratamiento de diferentes tipos de enfermedades inflamatorias autoinmunes y hematológicas. También en humanos, los inhibidores de JAKs se han mostrado eficientes para el tratamiento de dermatitis atópica, alopecia areata, psoriasis y vitíligo. Algunos de estos inhibidores son el tofacitinib, ruxolitinib, baricitinib y el oclacitinib. Esta última droga, oclacitinib, es de uso exclusivo en medicina veterinaria y estudios recientes han demostrado que tiene rápido efecto en la disminución deli prurito y lesiones de perros con dermatitis atópica. Este trabajo tuvo como objetivo revisar la literatura relacionada con esta nueva y prometedora clase de medicamentos, haciendo foco en el oclacitinib utilizado en medicina veterinaria.
Assuntos
Animais , Dermatite Atópica/terapia , Dermatite Atópica/veterinária , Inibidores de Proteínas Quinases/análise , Interleucinas , Janus Quinases/antagonistas & inibidores , Prurido/veterináriaRESUMO
INTRODUCTION: Current available treatments for inflammatory bowel disease (IBD) have some limitations and new options are needed. Several new molecules are being tested for the treatment of IBD and other immune-mediated inflammatory diseases. Among them, Janus kinase (JAK) inhibitors seem to have the lead, since tofacitinib has received regulatory approval in 2012 for the treatment of rheumatoid arthritis, and also it has shown a favorable risk-benefit ratio in phase 3 studies for ulcerative colitis, both in anti-TNF naïve and anti-TNF experienced patients. Other compounds with JAK inhibitory activity are also being tested with promising results. Areas covered: This review discusses the molecular aspects of the JAK-STAT pathway, which gives rationale for the use of JAK inhibitors in immune-mediated inflammatory diseases, especially in IBD. Different compounds with JAK inhibitory activity are presented, and relevant efficacy and safety data in IBD and other conditions are discussed. Expert commentary: It would not be surprising that in a foreseeable future many new orally administrated drugs will be available. This enhanced armamentarium will probably pose new dilemmas, in terms of drug positioning, escalation and de-escalation strategies, and combination therapy.