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2.
JAMA Dermatol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630455

RESUMO

This cohort study describes the clinical features, patient characteristics, and treatment of anti-melanoma differentiation­associated gene 5 (MDA5) dermatomyositis.

5.
JAMA Dermatol ; 160(1): 28-36, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910098

RESUMO

Importance: Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions. Objective: To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions. Data Sources: PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023. Study Selection: This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded. Data Extraction and Synthesis: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO. Main Outcomes and Measures: Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE. Results: The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04). Conclusions and Relevance: In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.


Assuntos
Artrite Reumatoide , Dermatite Atópica , Inibidores de Janus Quinases , Tromboembolia Venosa , Humanos , Masculino , Adulto , Inibidores de Janus Quinases/efeitos adversos , Tromboembolia Venosa/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-37566808

RESUMO

ABSTRACT: The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a critical role in the pathogenesis of many immune-mediated inflammatory diseases (IMIDs). Although Janus kinase inhibitors (JAKi) are an effective treatment for several IMIDs, they have come under scrutiny as a class due to a potential risk of venous thromboembolism (VTE) and cardiovascular (CV) events, specifically noted with the oral JAKi, tofacitinib, as reported in the ORAL Surveillance Trial of a high CV risk rheumatoid arthritis population. This trial resulted in a black box warning from the Food and Drug Administration and European Medicines Agency regarding risk of VTE and CV events that was extended across several types of JAKi (including topical ruxolitinib) when treating IMIDs, leading to considerable controversy. Included is an up-to-date review of the current and rapidly evolving literature on CV risk in patients with IMIDs on JAKi therapy, including identification of potential risk factors for future VTE and CV events on JAKi therapy. We suggest a comprehensive, multimodal, and systematic approach for evaluation of CV risk in patients considering taking JAKi and emphasize that cardiologists play an important role in risk stratification and mitigation for patients with high CV risk factors or on long-term JAKi therapies.

9.
Clin Cosmet Investig Dermatol ; 16: 803-820, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37025396

RESUMO

Alopecia areata is an autoimmune hair loss disorder with variations in distribution, duration, and severity. The disease is chronic and often follows an unpredictable course, frequently leading to stress and anxiety for those who suffer from it. Throughout the years more knowledge has been gained regarding pathogenesis, diagnostic tools, impact on quality of life, as well as treatment strategies for alopecia areata. However, challenges in treating and alleviating the burden of disease remain. In this article, we discuss updates regarding the pathogenesis and treatment of alopecia areata and highlight unmet needs of the condition, including a review of limitations of current treatments, accessibility to management strategies, and the need for disease awareness and advocacy.

11.
ACR Open Rheumatol ; 4(10): 912-922, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35903881

RESUMO

OBJECTIVE: Janus kinase (JAK) inhibition effectively treats immune-mediated inflammatory diseases (IMIDs); however, concern over the risk of major adverse cardiac events (MACE) and venous thromboembolism (VTE) remains. We aimed to evaluate the safety (VTE and MACE outcomes) of JAK inhibitors in the treatment of IMIDs. METHODS: A search in PubMed, Embase, and ClinicalTrials.gov databases was conducted for randomized clinical trials (RCTs) of JAK inhibitors across IMIDs. Primary outcomes were VTE and MACE with JAK inhibitors compared with placebo and active comparator arms stratified by follow-up time. RESULTS: Sixty-six RCTs enrolled 38,574 patients with a mean age of 48.8 years and a mean follow-up of 10.5 months. JAK inhibitors had a numerically higher rate of VTE when compared with controls (odds ratio [OR] 1.65; 95% confidence interval [CI]: 0.97-2.79), driven by trials with a follow-up duration of 12 or more months (OR 2.17; 95% CI: 1.16-4.05; Pinteraction = 0.05). When compared with active comparators, JAK inhibitors increased VTE in clinical trials with 12 or more months' versus less than 12 months' follow-up time (OR 2.38 [95% CI: 1.24-4.57] vs 0.30 [95% CI: 0.07-1.26], respectively; Pinteraction = 0.01). No increased risk of VTE was seen when comparing JAK inhibitors with placebo arms. For the outcome of MACE, the results were largely similar but did not reach statistical significance (OR 1.19; 95% CI: 0.86-1.64). CONCLUSION: JAK inhibitors when compared with active comparator arms increased the risk of VTE, which was dependent on duration of exposure. Future clinical trials with extended follow-up are needed to clarify the safety profiles of JAK inhibitors.

19.
J Drugs Dermatol ; 18(12): 1276-1279, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860218

RESUMO

Lichen planopilaris (LPP) is a cicatricial alopecia that often causes permanent hair loss. Pioglitazone, a peroxisome proliferator activated receptor-gamma (PPAR- γ) agonist, has demonstrated immunomodulatory properties that may offer an effective treatment modality. This retrospective analysis describes 23 patients with LPP treated with adjunctive pioglitazone. Most (18/25) demonstrated significant reduction in patient-reported symptoms and clinical signs of inflammation. No adverse effects were reported. J Drugs Dermatol. 2019;18(12):1276-1279.


Assuntos
Líquen Plano/tratamento farmacológico , PPAR gama/agonistas , Pioglitazona/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Masculino , Pessoa de Meia-Idade , Pioglitazona/farmacologia , Estudos Retrospectivos , Resultado do Tratamento
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