Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis
Objective: To look for the effectiveness and safety of pamapimod (a selective inhibitor from the alpha-isoform of p38 MAP kinase) as monotherapy in comparison to methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis symptoms (RA).
Methods: Patients were at random allotted to 1 of four treatment groups and received 12 days of double-blind treatment. One group received MTX (7.5 mg/week with planned escalation to twenty mg/week), and three groups received pamapimod (50, 150, or 300 mg) once daily. The main effectiveness finish point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 days. Secondary finish points incorporated ACR50 and ACR70 responses, vary from baseline within the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and alter from baseline in every parameter from the ACR core group of measures. Safety monitoring incorporated recording of adverse occasions (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of significant signs.
Results: Patients allotted to receive MTX and pamapimod had similar census and baseline characteristics. At week 12, less patients taking pamapimod had an ACR20 response (23%, 18%, and 31% within the 50-, 150-, and 300-mg groups, correspondingly) in contrast to patients taking MTX (45%). Secondary effectiveness finish points demonstrated an Pamapimod identical pattern. AEs were typically characterised as mild and incorporated infections, skin conditions, and dizziness. Pamapimod was generally well tolerated, however the 300-mg dose made an appearance to become more toxic than either the two lower doses or MTX.
Conclusion: The current results demonstrated that pamapimod wasn’t competitive with MTX in treating active RA.