RESUMO
PURPOSE: To report the long-term outcome of three refractory anterior scleritis cases successfully treated with tofacitinib, a Janus-associated kinase inhibitor. METHODS: Three patients with systemic autoimmune disease-associated anterior scleritis (two with rheumatoid arthritis and one with systemic lupus erythematosus), resistant to conventional immunomodulatory therapy, were subsequently treated with tofacitinib (10 mg/day). RESULTS: Tofacitinib resulted in complete resolution of scleritis in all patients. During the 39-78 months of follow-up, no recurrence of scleritis occurred, and no adverse effects associated with tofacitinib were noted. At the last follow-up, all patients were free of scleritis with two patients receiving tofacitinib monotherapy and one without. CONCLUSION: Tofacitinib can be a safe and effective treatment for noninfectious refractory scleritis, warranting further investigation in large clinical trials.
RESUMO
Bullous pemphigoid is an acquired autoimmune subepidermal blistering disease that can arise following exposure to systemic medication, referred to as drug-induced bullous pemphigoid. Drug-induced bullous pemphigoid is a rare but potentially serious immune-related adverse event that should be considered in patients with advanced malignancies undergoing immunotherapy, with immune checkpoint inhibitors emerging in particular as a well-documented drug association in drug-induced bullous pemphigoid. We present a 74-year-old female with recurrent metastatic programmed cell death-ligand 1-positive squamous cell carcinoma of the head and neck area who developed drug-induced bullous pemphigoid in the setting of immunotherapy with a novel immunoglobulin-like transcript 4 inhibitor (MK-4830) in combination with pembrolizumab. Treatment with upadacitinib, a Janus-associated kinase-1 inhibitor, was pursued for significantly disabling disease that was recalcitrant to standard therapies and ultimately transition to palliative care. Follow-up at 4 weeks demonstrated good response. This is the first report describing the use of a Janus-associated kinase inhibitor for the treatment of bullous pemphigoid.
RESUMO
A hyperinflammatory response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with coronavirus disease 2019 (COVID-19). Agents that inhibit components of the pro-inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the proinflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus-associated kinase (JAK)-inhibitor that interrupts the signaling of multiple cytokines implicated in COVID-19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin-converting-enzyme-2 upregulation. However, baricitinib's immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients' immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events, which is concerning given the proclivity towards a hypercoagulable state in patients with COVID-19. In this article, we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety, and current progress in COVID-19 clinical trials.