International Congress on Large Vessel Vasculitis and Polymyalgia Rheumatica

Background.HSD-1 differentially regulates intracellular glucocorticoid levels in the immune system and glucocorticoid toxicity target organs.SPI-62 is a potent HSD-1 inhibitor.Objective.To observe whether SPI-62 can both maintain prednisolone efficacy and reduce prednisolone toxicity in patients with PMR.Methods.Patients with PMR and who received prednisolone 10 mg/day continued treatment for 4 weeks without dose reduction.They additionally received SPI-62 6 mg/day or matching placebo (PBO-PSL10) for 2 weeks each.In sequential cohorts, during SPI-62 treatment the prednisolone dose was 10 (SPI-PSL10), 15 (SPI-PSL15), or 20 mg/day (SPI-PSL20).Relapse was defined when the investigator further increased the prednisolone dose to manage a participant's PMR symptoms.Participants completed daily numeric rating scales for pain, stiffness, and fatigue intensity, and pain chronicity, and Health Assessment Questionnaire-Disability Index during trial visits.Inflammatory, bone, and lipid biomarkers were measured at Baseline, Week 2, and Week 4. Insulin resistance (HOMA-IR) was calculated as fasting glucoseinsulin.Trial interpretation is based on descriptive statistics.Hepatic HSD-1 inhibition was monitored via urinary metabolites: (tetrahydrocortisol+allotetrahydrocortisol)/tetrahydrocortisone.Results.SPI-62 achieved 94.74.6% hepatic HSD-1 inhibition.Relapse incidence and descriptive statistics for other parameters are presented (Table I).PMR therapeutic control was reduced with SPI-PSL10 and SPI-PSL15, but not SPI-PSL20, compared to PBO-PSL10.Substantial improvements were observed on bone, lipid, and glycemic control parameters related to prednisolone toxicity with each SPI-62-containing regimen. Conclusion.In patients with PMR the combination of SPI-62 and prednisolone 20 mg, compared to prednisolone 10 mg alone, showed an improved benefit-risk profile comprised of similar efficacy and less evidence of prednisolone toxicity.