JAK Inhibition as a Potential Treatment Target in Systemic Lupus Erythematosus. Mediterranean journal of rheumatology Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules responsible for signal transduction of multiple cytokines and growth factors in different cell types, involved in the maintenance of immune tolerance. Thus, the dysregulation of this pathway plays a crucial role in the pathogenesis of multiple autoimmune, inflammatory, and allergic diseases and is an attractive treatment target. JAK inhibitors (JAKinibs) have been approved in the treatment of multiple autoimmune diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (SPA). In SLE, there is a plethora of ongoing trials evaluating their efficacy, with tofacitinib, baricitinib and deucravacitinib showing promising results, without major safety concerns. In this review, we will discuss the rationale of targeting JAKinibs in SLE and summarize the clinical data of efficacy and safety of JAKinibs in SLE patients. 10.31138/mjr.231123.jia

JAK inhibitors in systemic lupus erythematosus: Translating pathogenesis into therapy. Lupus Systemic lupus erythematosus (SLE) is a complex multi-organ autoimmune disease marked by the production of autoantibodies against nuclear structures, formation of immune complexes, and chronic inflammation triggered by their tissular deposition. SLE is characterized by alternating periods of relapse and remission and each flare has the potential to cause new organ damage related to either the disease process or the medication toxicity. Despite remarkable progress across its multiple domains, SLE is still an area with many unmet needs, calling for innovative and practical solutions. The efforts of the drug development programme in lupus have led to considerable growth in the last decade, owing to the approval of belimumab, anifrolumab, and voclosporin. The increasing understanding of the pathogenesis of the disease has enabled the exploration of novel therapeutic strategies. New discoveries in the intricate cytokine kaleidoscope of lupus have made the concept of targeted therapy an attractive and promising research focus. JAK inhibitors are oral targeted therapies approved for a wide variety of diseases across the Rheumatology, Gastroenterology, Dermatology, and Haematology fields. Multiple JAKis are currently being investigated in SLE. This paper aims to summarize existing data coming from both clinical trials and case reports regarding the use of JAK inhibitors in SLE. 10.1177/09612033241287594

Novel JAK inhibitors under investigation for systemic lupus erythematosus: - where are we now? Expert opinion on investigational drugs INTRODUCTION:Glucocorticoids and immunosuppressants are used to treat systemic lupus erythematosus (SLE). However, patients with SLE have poor long-term prognoses. This can be attributed to organ damage caused by flare-ups and drug toxicity due to the administration of nonspecific treatment. Therefore, SLE should be treated using therapeutic agents specific to its pathology. Janus kinase (JAK) inhibitors exert multitargeted effects by blocking the signaling of multiple cytokines. The use of JAK inhibitors has been approved to treat several inflammatory autoimmune diseases. Several clinical trials of JAK inhibitors for SLE treatment are ongoing. AREA COVERED:This review summarizes the basic and clinical significance of JAK inhibitors for treating SLE and the current status of the development of JAK inhibitors based on recent reports. EXPERT OPINION:SLE is a clinically and immunologically heterogeneous disease. Therefore, drugs targeting a single molecule require precision medicine to exert maximal therapeutic efficacy. JAK inhibitors can probably fine-tune the immune network via various mechanisms and broadly regulate complex immune-mediated pathologies in SLE. However, evidence is required to address some safety concerns associated with the use of JAK inhibitors in patients with SLE, including infections (particularly herpes zoster) and thromboembolism (particularly in the presence of concomitant antiphospholipid syndrome). 10.1080/13543784.2023.2264172