Jornal de doenças infecciosas e terapia

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Potential of Janus Kinase (JAK) Inhibitors for Allergic Conditions Complicating Rheumatoid Arthritis (RA): Suppressing the Multiple Immunopathogenic Pathway

Takashi Yamane, Akira Hashiramoto

Eosinophilic Pneumonia (EP) is a well-known form of antibiotic-resistant pneumonia with increased eosinophils, and Chronic EP (CEP) has a subacute course with respiratory symptoms lasting several months and progressive dyspnea. Although Glucocorticoid (GC) therapy shows a marked response in the early stages of CEP, there is no sufficient evidence for the optimal duration of GC administration and many patients are forced to continue GC maintenance therapy. Hence, adverse events associated with long-term administration such as osteoporosis and infections are problematic.

Rheumatoid Arthritis (RA) is a systemic autoimmune polyarthritis that recent strategic therapies using Disease Modifying Anti-Rheumatic Drugs (DMARDs), such as Methotrexate (MTX), and biologics have been promoted to induce disease remission, while GC is not recommended due to concerns about adverse events. The development of targeted synthetic DMARD, Janus Kinase (JAK) inhibitors, has also promoted the treatment strategy of RA. JAKs are members of the intracellular, nonreceptor protein tyrosine kinase family, which includes four JAKs (JAK1-3 and TYK2). Among them, a JAK1/2 inhibitor baricitinib, not only slow the progression of joint damages by inhibiting T helper type 1 (Th1) cytokines, but also demonstrates regulatory effects on Th2 cytokines such as IL-4, IL-5, and IL-13.

Recent reports have shown the association between RA and allergic diseases such as asthma and Atopic Dermatitis (AD), indeed, we also experienced a case of RA complicated CEP that the patient was weaned from longstanding GC by taking baricitinib.

Though values of GCs on various inflammatory and autoimmune diseases, adverse events associated with longterm administration negatively affect patients' quality of life and prognosis.

Based on the own experience, we discuss the possibility of tailor-made therapies that are effective for both the underlying disease and complications, utilizing the unique immunosuppressive effects of JAK inhibitors.