Single doses of p38 MAP kinase inhibitors or prednisolone affect CRP and IL-6 in patients with active Rheumatoid Arthritis (RA)

摘要: Purpose: To investigate the effects of single doses losmapimod, dilmapimod (inhibitors p38 MAPK) and prednisolone on biomarkers systemic inflammation (serum C-reactive protein (CRP) interleukin (IL)-6) in subjects with active rheumatoid arthritis (RA). Methods: Two randomized, double blind, placebo controlled, parallel group, dose studies investigated CRP IL-6 dose-response relationships for losmapimod (study A) B) patients RA stable weekly methotrexate. CRP, other exploratory were measured blood at baseline up to 72 hours post-dosing. Results: In study A, 51 randomized receive (7.5, 20 60 mg) or B, 77 15 25 (10, 50 placebo. Single caused a decrease circulating detectable 3 24 post-dose as well single-dose relationship 48 RA. All produced statistically significant reduction serum IL-6, but had no effect CRP. Dilmapimod any time. Conclusion: This response clinical design could be useful early development anti-inflammatory agents treatment arthritis. Inhibition both would increase confidence that new chemical entity may have potential deliver benefit Trial registration: [clinicaltrials.gov: NCT00256919 NCT00134693].