June 24, 2010 (Rome, Italy) — Tanezumab appears to be highly effective at reducing knee pain in patients with osteoarthritis (OA), according to the results of a double-blind randomized phase 3 trial presented here at the European League Against Rheumatism (EULAR) Congress 2010.
"All 3 doses of tanezumab were superior to placebo for all primary end points at week 16. In addition, for nearly all assessments, tanezumab was superior to placebo at all time points from week 4 on. The greatest benefit was observed with the 10 mg dose," M.J. Brown, MD, told meeting attendees. Dr. Brown is lead clinician for tanezumab at Pfizer in New London, Connecticut.
Dr. Brown also said that tanezumab was safe and well tolerated, but at least one expert in the audience took issue with that statement.
Tanezumab is an investigational monoclonal antibody targeted to nerve growth factor, and it is being studied in OA and other painful conditions.
After screening, 690 patients with severe OA of the knee were randomized as follows: 172 patients to placebo, 172 patients to intravenous injections of tanezumab 2.5 mg, 172 patients to tanezumab 5 mg, and 174 patients to tanezumab 10 mg. Tanezumab injections were administered at baseline and then every 8 weeks until week 24. The study ended at week 32.
At EULAR, Dr. Brown presented the results of a prespecified week 16 analysis of coprimary end points, consisting of the Western Ontario and McMaster Universities OA Index (WOMAC) pain and physical function subscale scores and patient global assessment (PGA).
The investigators enrolled patients with WOMAC pain subscale scores of 5 or higher, with physical function subscale scores of 4 or higher, and a PGA score for OA of fair, poor, or very poor. All patients had failed on nonopiate pain medications or were candidates for invasive interventions.
Females comprised about 60% of the study population. About 10% to 18% had Kellgren–Lawrence grade 4 OA.
Dr. Brown reported that 58% of placebo patients completed treatment to week 24, compared with 69% to 80% of those treated with tanezumab. One third of placebo patients and 12% to 20% of tanezumab patients discontinued treatment.
At week 16, patients in all 3 tanezumab groups had significant reductions in WOMAC pain subscale scores from baseline, compared with placebo (P = .015 for the 2.5 mg dose; P = .005 for the 5 mg dose; and P < .001 for the 10 mg dose).
Similar results were seen for change on WOMAC physical function subscale scores from baseline (P = .009, P < .001, and P< .001, respectively, for the 3 doses of tanezumab vs placebo). PGA scores were also significantly superior for all 3 doses of tanezumab, compared with placebo at week 16 (P = .001, P < .001, and P < .001, respectively).
"All 3 doses of tanezumab were statistically superior to placebo at every time point from week 4 on," Dr. Brown said.
Adverse events of any type were reported by 55% to 59.8% of the tanezumab groups and 49.3% of placebo group. Abnormal sensations, including paresthesia and hypoesthesia, were reported by 3% to 5% of the tanezumab-treated patients and by 1.2% to 1.7% of placebo-treated patients.
"We referred patients with abnormal sensations to a neurologist for consultation. There was some evidence of peripheral neuropathy in these few patients," Dr. Brown said.
Other common adverse events (occurring in more than 5% of patients) were arthralgia (2.9% to 72% for tanezumab vs 44.1% for placebo), peripheral edema (1.7% to 6.3% vs 0.6%, respectively), extremity pain (0.6% to 5.2% vs 2.9%, respectively), and upper respiratory tract infection (4.0% to 6.4% vs 4.1%).
Marc Hochberg, MD, professor of medicine and head of the Division of Rheumatology and Clinical Immunology at the University of Maryland in Baltimore, disagreed that the study demonstrated safety and efficacy.
"This product appears to be efficacious for the signs and symptoms of OA in this 24-week trial, with primary outcomes reported at week 16. The frequency of adverse events was high and there was a dose-related increase in discontinuations in the tanezumab group. I would like to see more detailed data about the adverse events, including the number needed to treat and the number needed to harm," Dr. Hochberg said.
Dr. Brown reports being an employee of Pfizer. Dr. Hochberg reports being a consultant for CORRONA, Abbott, Amgen, Bristol-Myers Squibb, Roche Pharmaceuticals, and Pfizer (but not on tanezumab).
European League Against Rheumatism (EULAR) Congress 2010. Abstract OP0157. Presented June 18, 2010.
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