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:/B> Patients receiving stable doses of MTX were randomized to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily [qd]) 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, DAS/EULAR response, and individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing, and immunology assessments. RESULTS:/B> On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31-43%) 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.

OBJECTIVE: To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid). METHODS: Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting). RESULTS: Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2%(p<0.001); drug-related diarrhea 3.7% vs 16.2%(p<0.001); one or more clinical AEs 52.9% vs 73.0%(p<0.001); GI AEs 28.9% vs 48.5%(p<0.001); NSAID-type GI AEs 18.6% vs 29.9%(p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7%(p<0.05); and discontinuations due to any AE 4.1% vs 9.1%(p=0.029). No significant differences were observed in efficacy. CONCLUSION: Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).