Publication:
Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review

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Date

2021-04-15

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Gómez-Arias, Pedro Jesús
Gómez-García, Francisco
Hernández-Parada, Jorge
Montilla-López, Ana María
Ruano, Juan
Parra-Peralbo, Esmeralda

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Springer Nature
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Abstract

Importance Type I interferon (IFN)-mediated monogenic autoinflammatory disorders (interferonopathies) are childhood-onset rare multisystemic diseases with limited treatment options. The Janus kinase (JAK) inhibitors are promising potential therapeutic candidates for immune-mediated chronic inflammatory skin diseases. Objective To review the use of JAK inhibitors to improve decision-making when treating interferonopathies with cutaneous manifestations. Evidence Review The MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science databases were searched for studies that used JAK protein inhibitors to treat IFN-related monogenic diseases with cutaneous manifestations in humans. The search results are reported using the scoping review approach. Findings Seventeen open-label studies assessing the efficacy of ruxolitinib, baricitinib, or tofacitinib reported variable responses in patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) and related syndromes, stimulator of IFN genes [STING]-associated vasculopathy with onset in infancy (SAVI), familial chilblain lupus (FCh-L), gain-of-function mutations of STAT1 (GOF-STAT1), or Aicardi-Goutiéres syndrome. JAK inhibitors improved clinical and analytical parameters and decreased flare numbers, plasma inflammatory markers, and expression of IFN-stimulated genes. BK viremia and upper respiratory infections were the most frequent and severe adverse events. Significant heterogeneity in efficacy assessment methods and poor reporting of safety events were detected. Conclusions and Relevance Evidence of the use of JAK inhibitors in patients with interpheronopathies is scarce and of low methodological quality. Future clinical trials should use validated scales and report drug safety in a more accurate way.

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Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Persons::Persons::Age Groups::Child
Medical Subject Headings::Information Science::Information Science::Information Storage and Retrieval::Databases as Topic::Databases, Bibliographic::PubMed::MEDLINE
Medical Subject Headings::Diseases::Virus Diseases::Viremia
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interferons::Interferon Type I
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Janus Kinases
Medical Subject Headings::Diseases::Respiratory Tract Diseases::Respiratory Tract Infections
Medical Subject Headings::Information Science::Information Science::Communications Media::Publications::Bibliography as Topic::Bibliometrics

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Keywords

CANDLE, SAVI, Familial chilblain lupus, JAK inhibitors, Autoinflammatory diseases, Interferon pathway, Ruxolitinib, Tofacitinib, Baricitinib, Viremia, Type I interferon, Interferonopathies, Inhibidores de las cinasas Janus, Enfermedades autoinflamatorias hereditarias, Interferón de tipo I, Bases de datos bibliográficas

Citation

Gómez-Arias PJ, Gómez-García F, Hernández-Parada J, Montilla-López AM, Ruano J, Parra-Peralbo E. Efficacy and Safety of Janus Kinase Inhibitors in Type I Interferon-Mediated Monogenic Autoinflammatory Disorders: A Scoping Review. Dermatol Ther. 2021 Jun;11(3):733-750