Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: a randomised, double-blind, multicentre, phase IIb study
| Autor: | Dorothy McCabe, Vibeke Strand, Abraham Simon-Campos, Judith Hey-Hadavi, Brinda Tammara, Ricardo Rojo, Frank Buttgereit, Eun Bong Lee, Astrid Genet |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male rheumatoid arthritis medicine.medical_specialty Adolescent Immunology Placebo Gastroenterology law.invention Arthritis Rheumatoid 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Rheumatology Randomized controlled trial Prednisone law Internal medicine medicine Fosdagrocorat Immunology and Allergy Humans Adverse effect Aged 030203 arthritis & rheumatology Aged 80 and over Creatinine treatment business.industry Middle Aged Phenanthrenes medicine.disease Organophosphates 030104 developmental biology Treatment Outcome chemistry Rheumatoid arthritis Antirheumatic Agents Drug Therapy Combination Female business disease activity Biomarkers medicine.drug |
| Zdroj: | RMD Open |
| ISSN: | 2056-5933 |
| Popis: | ObjectivesGlucocorticoids have anti-inflammatory, transrepression-mediated effects, although adverse events (AEs; transactivation-mediated effects) limit long-term use in patients with rheumatoid arthritis (RA). We evaluated the efficacy and safety of fosdagrocorat (PF-04171327), a dissociated agonist of the glucocorticoid receptor, versus prednisone or placebo.MethodsIn this 12-week, phase II, randomised controlled trial, 323 patients with moderate to severe RA were randomised 1:1:1:1:1:1:1 to fosdagrocorat (1 mg, 5 mg, 10 mg or 15 mg), prednisone (5 mg or 10 mg) or placebo, once daily. The primary endpoints (week 8) were American College of Rheumatology 20% improvement criteria (ACR20) responses, and percentage changes from baseline in biomarkers of bone formation (procollagen type 1 N-terminal peptide [P1NP]) and resorption (urinary N-telopeptide to urinary creatinine ratio [uNTx:uCr]). Safety was assessed.ResultsACR20 responses with fosdagrocorat 10 mg and 15 mg were superior to placebo, and fosdagrocorat 15 mg was non-inferior to prednisone 10 mg (week 8 model-predicted ACR20 responses: 47%, 61%, 69% and 73% vs 51%, 71% and 37% with fosdagrocorat 1 mg, 5 mg, 10 mg and 15 mg vs prednisone 5 mg, 10 mg and placebo, respectively). Percentage changes from baseline in P1NP with fosdagrocorat 1 mg, 5 mg and 10 mg met non-inferiority criteria to prednisone 5 mg. Corresponding changes in uNTx:uCr varied considerably. All fosdagrocorat doses reduced glycosylated haemoglobin levels. AEs were similar between groups; 63 (19.5%) patients reported treatment-related AEs; 9 (2.8%) patients reported serious AEs. No patients had adrenal insufficiency, treatment-related significant infections or laboratory abnormalities. No deaths were reported.ConclusionIn patients with RA, fosdagrocorat 10 mg and 15 mg demonstrated efficacy similar to prednisone 10 mg and safety similar to prednisone 5 mg.Trial registration numberNCT01393639 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|