Investigational IV Golimumab Inhibits Structural Damage in RA

WASHINGTON, DC — An investigational formulation of intravenous golimumab achieves significant inhibition of radiographic progression over 1 year compared with placebo in patients with active moderate to severe rheumatoid arthritis (RA), according to phase 3 data presented here at ACR 2012. All patients had active RA despite background treatment with methotrexate.

"These phase 3 data show treatment with intravenous golimumab plus methotrexate induced and maintained improvements in the signs and symptoms of rheumatoid arthritis and inhibited the progression of structural damage," said senior author Rene Westhovens, MD, professor at the Department of Rheumatology, KU Leven, Belgium. The benefits persisted from week 24 through week 52, he added.

Dr. Michael Weinblatt

Michael Weinblatt, MD, from Brigham and Women's Hospital in Boston, Massachusetts, presented formal results of the study.

GO-FURTHER was a phase 3, international, multicenter, double-blind, placebo-controlled trial that included 592 adults with RA who had been receiving background methotrexate treatment for at least 3 months and had active moderate to severe arthritis, as shown by the presence of at least 6 tender and 6 swollen joints. Patients were randomly assigned in a 2:1 ratio to receive a 30-minute IV infusion of golimumab 2 mg/kg or placebo plus methotrexate at weeks 0, 4, and then every 9 weeks.

At week 16, patients in the placebo group with less than a 10% improvement in signs and symptoms of RA were allowed to cross over to IV golimumab at week 16 and week 20. By week 24, all patients randomly assigned to placebo had crossed over to IV golimumab.

Analysis of x-rays at week 24 showed significant inhibition of the progression of structural damage in a greater percentage of patients receiving IV golimumab compared with placebo; the inhibition of structural damage was maintained through week 52 in patients originally randomly assigned to IV golimumab and in those originally assigned to placebo who crossed over to IV golimumab.

Radiographic progression was assessed by the change from baseline in van der Hejde-Sharp (vdH-S) scores, which measure joint destruction, joint erosion, and joint space narrowing; higher scores indicate greater structural damage. At week 24, mean change from baseline in vdH-S score was 0.03 in the IV golimumab group vs 1.09 for the placebo patients (P < .001). At week 52, mean change from baseline in vdH-S score was 0.13 for IV golimumab-treated patients vs 1.22 for placebo patients who crossed over to IV golimumab during the trial (P < .001).

From week 24 to week 52, those randomly assigned to IV golimumab and those who crossed over to IV golimumab treatment had a mean change in total vdH-S scores of 0.15 and 0.12, respectively.

"This supports the inhibition of structural damage progression in all patients who received IV golimumab," Dr. Westhovens stated.

Safety Not an Issue

No new safety concerns were raised about IV golimumab from those reported at 24 weeks. At 24 weeks, adverse events were reported in 53% of IV golimumab-treated patients and in 49% of those who received placebo; serious adverse events were reported in 4% and 2%, respectively.

At week 52, adverse events were reported in 65% and serious adverse events in 9%; at that time point, all patients were taking IV golimumab.

Subcutaneous golimumab is approved by the US Food and Drug Administration for use in combination with methotrexate for the treatment of moderate to severe RA and for the treatment of active psoriatic arthritis with or without methotrexate and active ankylosing spondylitis.

According to Eric L. Matteson, MD, chair of the Department of Rheumatology at the Mayo Clinic, in Rochester, Minnesota, an IV formulation of golimumab will have some advantages over a subcutaneous injection formulation.

"A lot of patients will find intravenous therapy more convenient than subcutaneous injections, especially if they have difficulty doing self-injecting. Further, having IV golimumab may allow for great flexibility in dosing, although this has not been explored in great detail," Dr. Matteson commented.

Dr. Weinblatt and Dr. Westhovens received funding from Janssen Research and Development, LLC. Dr. Matteson disclosed financial ties with Centecor Inc/Johnson & Johnson, Genentech and Biogen IDEC Inc, Hoffman-La Roche Inc, Human Genome Sciences Inc, Pfizer Inc, Novartis Pharmaceutical Corporation, Roche Pharmaceuticals, UCB Group, Centocor Inc, Horizon Pharma, and Novartis Pharmaceutical Corp.

ACR 2012: Abstract 812. Presented November 11, 2012.