Clofutriben to Improve the Benefit-Risk Profile of Prednisolone in Patients with Polymyalgia Rheumatica

FRANK HARTMUT DR. BUTTGEREIT¹, Andrea Everding², Ioana Andreica³, Herbert Kellner⁴, Florian Schuch⁵, Tonya K Marmon⁶, Frank S Czerwiec⁷, Ketan Desai⁸ and David A Katz⁹, ¹Charité University Medicine Berlin, Berlin, Germany, ²Hamburger Rheuma Forschungszentrum II, Hamburg, Germany, ³Rheumazentrum Ruhrgebiet, Bochum, Germany, ⁴Schwerpunktpraxis f�r Rheumatologie und Gastroenterologie, Munich, Germany, ⁵PGRN, Erlangen, Germany, ⁶Marmon Biostatistics, Seattle, WA, ⁷Sparrow Pharmaceuticals, Portand, OR, ⁸IMC, Easton, PA, ⁹Sparrow Pharmaceuticals, Portland, OR

Meeting: ACR Convergence 2024

Keywords: clinical trial, corticosteroids, Drug toxicity, glucocorticoids, Polymyalgia Rheumatica (PMR)

Session Information

Date: Saturday, November 16, 2024

Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) differentially regulates intracellular glucocorticoid levels in the immune system and glucocorticoid toxicity target organs. Clofutriben is a potent HSD-1 inhibitor. We sought to observe whether clofutriben can both maintain prednisolone efficacy and reduce prednisolone toxicity in patients with polymyalgia rheumatica (PMR).

Methods: Patients with PMR and who received prednisolone 10 mg/day continued treatment for 4 weeks without dose reduction. They additionally received clofutriben 6 mg/day or matching placebo (PBO-PSL10) for 2 weeks each. In sequential cohorts, during clofutriben treatment the prednisolone dose was 10 (CLO-PSL10), 15 (CLO-PSL15), or 20 mg/day (CLO-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 glucose

insulin. Trial interpretation is based on descriptive statistics. Hepatic HSD-1 inhibition was monitored via urinary metabolites: (tetrahydrocortisol+allotetrahydrocortisol)/tetrahydrocortisone.

Results: Clofutriben achieved 94.7±4.6% hepatic HSD-1 inhibition. Relapse incidence and descriptive statistics for other parameters are presented (Table). PMR therapeutic control was reduced with CLO-PSL10 and CLO-PSL15, but not CLO-PSL20, compared to PBO-PSL10. Substantial improvements were observed on bone, lipid, and glycemic control parameters related to prednisolone toxicity with each clofutriben-containing regimen.

Conclusion: In patients with PMR the combination of clofutriben 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.

Disclosures: F. DR. BUTTGEREIT: AbbVie, 2, 5, 6, Gruenenthal, 2, Horizon Therapeutics, 2, 5, Pfizer, 6, Sanofi, 2, 5, 6, Sparrow Pharmaceuticals, 1, 5; A. Everding: Sparrow Pharmaceuticals, 5; I. Andreica: AbbVie/Abbott, 6, Amgen, 2, Boehringer-Ingelheim, 2, Chugai, 2, 6, Eli Lilly, 2, 5, 6, Galapagos, 2, Gilead, 6, Merck/MSD, 6, Novartis, 2, 6, Pfizer, 2, 6, SOBI, 2, 6, Sparrow Pharmaceuticals, 5, Takeda, 2, UCB, 2, 6; H. Kellner: Sparrow Pharmaceuticals, 5; F. Schuch: AbbVie/Abbott, 2, 5, 6, Eli Lilly, 2, 5, 6, Galapagos, 2, 5, 6, Novartis, 2, 5, 6, Sparrow Pharmaceuticals, 5; T. Marmon: Sparrow Pharmaceuticals, 7; F. Czerwiec: Sparrow Pharmaceuticals, 3, 8; K. Desai: Sparrow Pharmaceuticals, 7; D. Katz: Sparrow Pharmaceuticals, 3, 4, 8, 10.

To cite this abstract in AMA style:

DR. BUTTGEREIT F, Everding A, Andreica I, Kellner H, Schuch F, Marmon T, Czerwiec F, Desai K, Katz D. Clofutriben to Improve the Benefit-Risk Profile of Prednisolone in Patients with Polymyalgia Rheumatica [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/clofutriben-to-improve-the-benefit-risk-profile-of-prednisolone-in-patients-with-polymyalgia-rheumatica/. Accessed .

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