The FINANCIAL -- Phase 3 study findings presented showed that patients with active moderate to severe rheumatoid arthritis
who received an investigational intravenous formulation of
the anti-tumor necrosis factor (TNF)-alpha therapy SIMPONI demonstrated significant
improvements in signs and symptoms and disease activity.
Investigators reported nearly 60 percent of patients receiving SIMPONI I.V. achieved a 20 percent improvement in arthritis signs and symptoms at week 14, the study’s primary endpoint, and more than 80 percent of patients demonstrated meaningful improvements in disease activity as assessed by European League Against Rheumatism criteria at week 14. Results from the Janssen Research & Development, LLC, (Janssen)-sponsored study were presented at the 2012 EULAR Annual Congress and the study appears in the June 1, 2012 Online First feature in Annals of the Rheumatic Diseases.
“The data show the significant benefits of SIMPONI in improving the pain, stiffness and swelling associated with rheumatoid arthritis when administered intravenously,” said Rene Westhovens, M.D., Ph.D., Professor at the Department of Rheumatology, KU Leuven, Belgium, and study investigator. “Marked improvements were seen at week 14 and increased through week 24 in patients receiving SIMPONI I.V. induction and maintenance therapy.”
In the Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered Intravenously, in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy (GO-FURTHER) trial, patients with active RA despite treatment with methotrexate were randomized 2:1 to receive a 30 (+/- 10) minute infusion of SIMPONI I.V. 2 mg/kg (n=395) or placebo (n=197) plus methotrexate at weeks 0, 4 and then every 8 weeks. At week 14, 59 percent of patients receiving SIMPONI I.V. achieved at least a 20 percent improvement in signs and symptoms according to American College of Rheumatology (ACR) criteria (ACR 20) and 30 percent achieved at least a 50 percent improvement in ACR criteria (ACR 50) compared with 25 and 9 percent of patients receiving placebo, respectively (P < 0.001). Significant improvements in ACR 20 and ACR 50 were observed at week 2, after a single SIMPONI I.V. infusion as 33 percent of patients achieved an ACR 20 response versus 12 percent of patients receiving placebo (P < 0.001), and 6 percent of patients achieved an ACR 50 response versus 3 percent of patients receiving placebo, respectively. At week 24, 63 percent of patients receiving SIMPONI I.V. achieved an ACR 20 response versus 32 percent of patients receiving placebo, and 35 percent of patients receiving SIMPONI I.V. achieved an ACR 50 response versus 13 percent of patients receiving placebo (P < 0.001 for both comparisons).
Patients in the SIMPONI I.V. group also reported statistically significant improvements in EULAR/Disease Activity Score (DAS) 28 C-reactive protein (CRP) moderate or good responses. At week 14, 81 percent of patients receiving SIMPONI I.V. achieved moderate or good EULAR/DAS 28 CRP response compared with 40 percent of patients receiving placebo (P < 0.001). Significant improvements also were observed at week 2 after a single SIMPONI I.V. infusion as 65 percent of patients achieved moderate or good EULAR/DAS 28 CRP response compared with 19 percent of patients receiving placebo (P < 0.001). The EULAR/DAS 28 is a measure of disease activity in patients with RA that is calculated by assessing the number of tender and swollen joints (among a total of 28), inflammation and the patient’s assessment of global health. CRP is a type of protein produced in the liver and is expressed during episodes of acute inflammation associated with RA.
According to Johnson & Johnson, patients receiving SIMPONI I.V. also achieved clinically relevant improvements in physical function, as measured by the Health Assessment Questionnaire, as compared with the placebo group at week 14 (68 percent vs. 43 percent, P < 0.001) and week 24 (68 percent vs. 45 percent, P < 0.001). HAQ assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and other activities of daily living).
Adverse events (AEs) were reported in 47 percent of patients receiving SIMPONI I.V. and 44 percent of patients receiving placebo at week 16, and in 53 percent of patients receiving SIMPONI I.V. and 49 percent of patients receiving placebo at week 24. Serious AEs were reported in more SIMPONI I.V.-treated patients (4 percent) than placebo-treated patients (2 percent) through week 24. The most common serious AEs were serious infections, 1 percent in the SIMPONI I.V. group versus 0 percent in the placebo group. No cases of tuberculosis, serious opportunistic infections, congestive heart failure or demyelination were reported. Through week 24, the proportion of infusions with infusion reactions in the SIMPONI I.V. versus placebo groups were 1.1 percent versus 0.2 percent, respectively, (3.5 percent and 0.5 percent of patients, respectively) with a median infusion time of 30 minutes. There were no serious infusion reactions. One malignancy (breast cancer) was reported in the SIMPONI I.V. group through week 24, and one patient in the placebo group died of a presumed stroke.