New Phase 3 Data Show Simponi Intravenous Formulation Significantly Improved Rheumatoid Arthritis Signs and Symptoms in Patients with Active Disease

Phase 3 study findings showed that patients with active moderate to severe rheumatoid arthritis (RA) who received an investigational intravenous (IV) formulation of the anti-tumor necrosis factor (TNF)-alpha therapy Simponi (golimumab) [hereafter referred to as Simponi I.V.] demonstrated significant improvements in signs and symptoms and disease activity. Investigators reported nearly 60% of patients receiving Simponi I.V. achieved a 20% improvement in arthritis signs and symptoms at week 14, the study’s primary endpoint, and more than 80% of patients demonstrated meaningful improvements in disease activity as assessed by European League Against Rheumatism (EULAR) 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, MD, PhD, 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% achieved at least a 50% improvement in ACR criteria (ACR 50) compared with 25% and 9% 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% of patients achieved an ACR 20 response versus 12% of patients receiving placebo (P < 0.001), and 6% of patients achieved an ACR 50 response versus 3% of patients receiving placebo, respectively. At week 24, 63% of patients receiving Simponi I.V. achieved an ACR 20 response versus 32 percent of patients receiving placebo, and 35% of patients receiving Simponi I.V. achieved an ACR 50 response versus 13% 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% of patients receiving Simponi I.V. achieved moderate or good EULAR/DAS 28 CRP response compared with 40% of patients receiving placebo (P < 0.001). Significant improvements also were observed at week 2 after a single Simponi I.V. infusion as 65%of patients achieved moderate or good EULAR/DAS 28 CRP response compared with 19% 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.

Patients receiving Simponi I.V. also achieved clinically relevant improvements in physical function, as measured by the Health Assessment Questionnaire (HAQ) [improvement in HAQ greater than 0.25 from baseline], as compared with the placebo group at week 14 (68% vs. 43%, P < 0.001) and week 24 (68% vs. 45%, 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% of patients receiving Simponi I.V. and 44% of patients receiving placebo at week 16, and in 53% of patients receiving Simponi I.V. and 49% of patients receiving placebo at week 24. Serious AEs were reported in more Simponi I.V.-treated patients (4%) than placebo-treated patients (2%) through week 24. The most common serious AEs were serious infections, 1% in the Simponi I.V. group versus 0% 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% versus 0.2% respectively, (3.5% and 0.5% 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.

Results of SIMPONI I.V. on Rheumatoid Arthritis Associated Fatigue

A second abstract presented at the meeting evaluated the association of fatigue with physical function and disease activity in patients with RA, and the impact of treatment with Simponi I.V. on fatigue based on data from the GO-FURTHER trial. Using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, investigators found that patients enrolled in the GO-FURTHER trial experienced significant fatigue at baseline with a FACIT-Fatigue score of 25.5 (scores range from 0-52 with high scores representing less fatigue). A significantly greater proportion of patients receiving Simponi I.V. (58%) achieved clinically meaningful improvement in fatigue at week 12 compared with patients receiving placebo (43%), and improvements at week 24 of the study were reported in 66% of Simponi I.V.-treated patients compared with 40% of patients receiving placebo (P < 0.001). The FACIT-Fatigue questionnaire assesses patient-reported physical, social/family, emotional and functional well-being for those living with a chronic illness to evaluate disease-related fatigue. Clinically meaningful improvement in fatigue was defined as at least a four point increase in FACIT-Fatigue scores.

“Severe fatigue is common in patients with rheumatoid arthritis,” said Professor Westhovens. “This analysis of the GO-FURTHER study showed patients who are inadequately responsive to methotrexate and treated with Simponi I.V.. reported significant improvements in clinical symptoms of fatigue.”

SOURCE: Janssen