1032. Janus Kinase Inhibition for Refractory Post-infectious Inflammatory Response in Previously Healthy Patients with Cryptococcal Meningoencephalitis

Abstract

Abstract Background Post-infectious inflammatory response syndrome(PIIRS) is a previously reported complication of non-HIV cryptococcal meningitis (CM) involving a pathological T cell-mediated neuroinflammatory response once the fungus has been cleared. Although corticosteroids have been successfully used as therapy, side effects preclude prolonged use. Additionally, alternative targeted agents may be required as adjunctive therapy in steroid-refractory PIIRS. We report the clinical course in 3 patients in whom Janus kinase (JAK) inhibitor use led to favorable outcomes when used along with corticosteroids. Methods Medical records of three previously healthy CM-PIIRS patients admitted to the NIH between January 2021 to December 2021 were used to prepare this report. All were transferred from another facility due to worsening neurological status. Neurological exam and radiological findings were compared at baseline and one month after ruxolitinib initiation. CSF parameters including cellular markers of T-cell inflammation (HLA-DR+ CD4+ and HLA-DR+ CD8 cells and monocytes) and soluble CSF cytokines, including IL-6 and sCD25, were also included in the comparison. Results One patient was on 1mg/kg oral prednisone for 8 months with no improvement in symptoms despite VP shunt placement. The other two had also been on moderate-dose oral steroids for approximately 6 weeks for a recent diagnosis of PIIRS. All three were started on ruxolitinib (5-10 mg PO BID) as an adjunct to prednisone with a significant improvement in their neurological status, CSF inflammatory markers, and radiological findings. CSF fungal cultures remained negative with no occurrence of adverse events 3 months after ruxolitinib initiation. Therapy with ruxolitinib allowed continued corticosteroid taper without clinical flairs of disease in each patient. Conclusion The selective JAK1/2 inhibitor, ruxolitinib, was safe in a small group of HIV-negative patients with CM. This agent may offer promise in conjunction with corticosteroids in the treatment of non-HIV CM patients with refractory PIIRS who are at risk for adverse side effects related to prolonged steroid use. Further study will be required to determine efficacy, tolerability and ability to reduce corticosteroid use. Disclosures All Authors: No reported disclosures.