Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy

• Published in: Annals of the rheumatic diseases Vol. 69; no. 2; pp. 364 - 367
• Main Authors: Alten, R E, Zerbini, C, Jeka, S, Irazoque, F, Khatib, F, Emery, P, Bertasso, A, Rabbia, M, Caulfield, J P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.02.2010; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Aged; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Biomarkers - blood; Bones, joints and connective tissue. Antiinflammatory agents; C-Reactive Protein - metabolism; Clinical and epidemiological research; Clinical trials; Diseases of the osteoarticular system; Double-Blind Method; Drug Therapy, Combination; Humans; Immunomodulators; Infections; Inflammatory joint diseases; Laboratories; Medical sciences; Methotrexate; Methotrexate - adverse effects; Methotrexate - therapeutic use; Middle Aged; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; Pharmacology. Drug treatments; Placebos; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyridones - adverse effects; Pyridones - therapeutic use; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Rheumatoid arthritis; Rheumatology; Severity of Illness Index; Treatment Outcome; Young Adult; Antineoplastic agent; Human; Immunopathology; Toxicity; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Immunomodulator; Chronic; Treatment; Rheumatoid arthritis; Pamapimod; Antirheumatic agent; Methotrexate
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2008.104802

Objective:To determine the efficacy and safety of pamapimod in adult patients with active rheumatoid arthritis (RA) who had an inadequate clinical response to methotrexate (MTX).Methods:Patients receiving stable doses of MTX were randomised to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily) or matching placebo. The primary efficacy measure was the proportion of patients with ⩾20% improvement in RA based on the American College of Rheumatology criteria (ACR20) at 12 weeks. Secondary measures were ACR50, Disease Activity Score (DAS)/European League Against Rheumatism (EULAR) responses and the individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing and immunology assessments.Results:On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31% to 43%) was not significantly different from placebo (34%). Secondary efficacy end points showed a similar pattern. AEs were typically mild and included infections, gastrointestinal disturbances, dizziness and rashes; AEs resulting in discontinuation of study drug were primarily attributed to infections.Conclusion:In patients with active RA receiving stable doses of MTX, pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.