Results from a Phase 2 rheumatoid arthritis ( RA ) study assessing the safety and efficacy of Golimumab ( CNTO 148 ), a fully-human anti-TNF-alpha therapy, showed that it achieved the primary endpoint of the study.

In this dose-ranging trial, more than 60 percent of patients with moderately to severely active rheumatoid arthritis treated with Golimumab and Methotrexate ( MTX ) experienced at least 20 percent improvement in arthritis symptoms at week 16.

Additionally, one-quarter of patients receiving Golimumab and Methotrexate achieved remission as evaluated by Disease Activity Score 28 ( DAS28 ).

Golimumab, developed by Centocor, Inc. and Schering-Plough, is a fully-human anti-TNF-alpha IgG1 monoclonal antibody that targets and neutralizes both the soluble and the membrane-bound form of TNF-alpha. Golimumab is currently being investigated for administration by either subcutaneous ( SC ) injection or intravenous ( IV ) infusion.

Data from the study showed that significantly more patients in all groups receiving subcutaneous injections of Golimumab plus Methotrexate achieved ACR 50 response ( marked improvement in arthritis symptoms according to the American College of Rheumatology scoring criteria ) versus patients receiving placebo plus Methotrexate.

Adults with active RA for at least three months' duration despite Methotrexate therapy were randomized to one of five treatment groups: placebo every two weeks or Golimumab 50 or 100 mg every two weeks or every four weeks.
All patients received stable doses of Methotrexate of greater than or equal to 10 mg/week.

After just 16 weeks of treatment, 62 percent of all patients receiving Golimumab ( combined Golimumab treatment groups ) experienced at least 20 percent improvement in arthritis symptoms ( ACR 20 ), compared with 37 percent of placebo-treated patients ( P = 0.008 ).

Additionally, at week 16, 31 percent of patients in the combined golimumab treatment groups achieved ACR 50, and 12 percent achieved ACR 70, compared with six percent and zero percent, respectively, of patients in the placebo group.
All individual Golimumab treatment groups achieved higher ACR 20 response rates than placebo.
Golimumab 50 mg every four weeks ( 63 percent ) and Golimumab 100 mg every two weeks ( 79 percent ) were statistically significantly more effective than placebo ( 37 percent ) in achieving an ACR 20 response ( P = 0.031 and P < 0.001, respectively ).

Patients in the Golimumab plus Methotrexate treatment group also achieved remission, as assessed by DAS 28, which measures tender and swollen joints, inflammation and overall disease activity including measurement of serum C-reactive protein ( CRP ) levels. After 16 weeks of treatment, 27 percent of patients in the combined group achieved remission as assessed by DAS28 compared with six percent of patients receiving Methotrexate alone (P = 0.007).

Adverse events in the Golimumab groups were similar to those in the Methotrexate group. Serious adverse events were reported in eight percent of patients in the combined Golimumab group, compared with six percent in the Methotrexate group.
No deaths, cases of tuberculosis or other opportunistic infections were reported and serious infections were uncommon. One case each of lung cancer, congestive heart failure, cardiac tamponade, and two cases of pneumonia were reported among patients treated with Golimumab.

Source: Centocor, 2005


XagenaMedicine2005