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Phase II Efficacy Seen With New TNF Blocking Agent


 

AMSTERDAM — The therapeutic options for patients with rheumatoid arthritis who do not respond to methotrexate alone continue to expand, with a new tumor necrosis factor-α blocker showing efficacy in a phase II trial.

In preclinical studies, the human monoclonal antibody golimumab was shown to be more effective at neutralizing tumor necrosis factor-α (TNF-α) than the other currently available biologic agents, Dr. Jonathan Kay wrote in a poster session at the annual European Congress of Rheumatology.

And while golimumab must be given subcutaneously, the dosing interval is once every 4 weeks rather than twice weekly as is the case with etanercept, or every other week as with adalimumab. Because the drug can be given once a month, it may provide a convenient alternative for patients, Dr. Kay told RHEUMATOLOGY NEWS in an interview.

The investigators randomly assigned 172 patients with rheumatoid arthritis (RA) of at least 3 months' duration to placebo or treatment with golimumab with one of four dosages: 50 mg every 2 weeks, 50 mg every 4 weeks, 100 mg every 2 weeks, or 100 mg every 4 weeks. All patients also were on stable doses of methotrexate.

At week 16, 62% of patients who were receiving golimumab plus methotrexate achieved an American College of Rheumatology 20 response, which was the primary end point, compared with 37% of those patients who were receiving placebo plus stable doses of methotrexate, according to Dr. Kay of the rheumatology unit at Massachusetts General Hospital, Boston.

A secondary end point of the trial was the Disease Activity Score 28 response to active and placebo treatments.

This outcome measure can be calculated using either the erythrocyte sedimentation rate or C-reactive protein levels, and patients' responses to therapies are categorized as good, moderate, remission, and nonresponse.

Using the erythrocyte sedimentation rate, Disease Activity Score 28 remission plus good/moderate responses were seen in 72% and 10% of the golimumab and placebo groups, respectively, and in 74% and 27%, respectively, using C-reactive protein levels.

Serious adverse events were reported by 8% of patients receiving golimumab plus methotrexate and by 5.9% of those receiving methotrexate plus placebo.

“Clinically relevant” adverse events reported in the golimumab group included two cases of pneumonia, one case of heart failure, one case of lung cancer, and one case of cardiac tamponade, Dr. Kay reported.

There were no deaths or cases of tuberculosis or opportunistic infections, however.

The phase II study was supported by Centocor Research and Development Inc. The pharmaceutical company has initiated Phase III studies that are underway to evaluate golimumab in patients with RA, psoriatic arthritis, and ankylosing spondylitis.

The drug is being given in doses of 50 or 100 mg every 4 weeks in these trials, which will follow patients for 5 years.

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