Intravenous Golimumab Inhibits Radiographic Progression of RA in Phase III Trial
Patients show significant improvements through 1 year (Nov. 12)In new phase III findings, treatment with the investigational intravenous (IV) drug golimumab (Janssen) –– a tumor necrosis factor (TNF) inhibitor –– significantly inhibited radiographic progression in patients with active moderate to severe rheumatoid arthritis (RA) despite treatment with methotrexate.
Analysis of the patients' X-rays showed significant inhibition of the progression of structural damage at week 24 in more patients receiving IV golimumab plus methotrexate than in those receiving placebo plus methotrexate. The inhibition of the progression of structural damage was maintained in patients randomized to IV golimumab through week 52, and inhibition of structural damage progression was observed at week 52 in patients receiving placebo who crossed over to IV golimumab at week 24. Treatment with IV golimumab plus methotrexate also led to improvements in signs and symptoms and in disease activity, with nearly 60% of patients achieving at least a 20% improvement in the American College of Rheumatology (ACR 20) score at week 14 (the study's primary endpoint), and with nearly two-thirds of patients achieving that response at week 52.
The new data are being presented at the 2012 Annual Meeting of the American College of Rheumatology.
In September 2012, the manufacturer submitted a Biologics License Application (BLA) to the FDA, requesting approval of IV golimumab in combination with methotrexate for the treatment of adults with moderately to severely active RA. Golimumab is currently marketed as Simponi –– a subcutaneous injection approved by the FDA for the treatment of moderately to severely active RA with methotrexate; for active psoriatic arthritis alone or with methotrexate; and for active ankylosing spondylitis.
In the phase III, multicenter, randomized, double-blind, placebo-controlled GO-FURTHER (GOlimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered IntravenoUsly, in Subjects with Active RheumaToid ArtHritis DEspite MethotRexate Therapy) trial, patients were randomized to receive IV golimumab 2 mg/kg or placebo via a 30-minute infusion plus methotrexate at weeks 0 and 4 and then every 8 weeks. Nonresponders to placebo at week 16 were crossed over to receive IV golimumab, and all remaining patients receiving placebo were crossed over at week 24.
Radiographic progression was assessed by the change from baseline in van der Heijde-Sharp (vdH-S) scores –– an X-ray measure of joint destruction, including joint erosion and joint- space narrowing, in which higher scores indicate greater structural damage.
At week 24, patients receiving IV golimumab had a mean change in the total vdH-S score of 0.03 from baseline, compared with a mean change of 1.09 in the placebo group (P < 0.001). At week 52, patients who received the 52-week regimen of IV golimumab had a mean change of 0.13 from baseline, compared with a mean change of 1.22 in patients who crossed over from placebo to IV golimumab during the trial (P < 0.001). Patients randomized to IV golimumab and those in the crossover group had mean changes in the total vdH-S score of 0.15 and 0.12, respectively, from week 24 to 52.
Significant proportions of patients receiving IV golimumab also demonstrated improvements in signs and symptoms compared with patients receiving placebo, according to ACR scores, European League Against Rheumatism (EULAR)/Disease Activity Score (DAS) 28 C-reactive protein (CRP) response criteria, and Health Assessment Questionnaire (HAQ) disability scores at weeks 14 and 24. Most of the patients who achieved an ACR 20, ACR 50, ACR 70, and EULAR/DAS 28 CRP good/moderate response by week 24 maintained the response through week 52 (82% of ACR 20 responders; 72% of ACR 50 responders; 61% of ACR 70 responders; and 80% demonstrating a DAS28-CRP good/moderate response). The EULAR/DAS 28 CRP 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), the serum CRP level (an indicator of inflammation), and the patient's assessment of global health.
Source: Johnson & Johnson; November 12, 2012.