Study Finds Anti-NGF Factor Effective for Hip Arthritis

Abstract

Treatment with the anti–nerve growth factor (NGF) tanezumab was associated with significant improvements over placebo in pain, physical function, and Patient's Global Assessment of osteoarthritis (OA) results, after 16 weeks in a phase III study of patients with OA of the hip. In the randomized, double-blind, placebo-controlled study of 621 patients with painful hip OA, treatment with tanezumab (an “anti-NGF”) was also well tolerated, according to Dr. Mark Brown and his associates. The study was funded by Pfizer, the manufacturer of tanezumab, and Dr. Brown and three of the five other authors are full-time employees of the company. Tanezumab “may eventually be useful in OA patients who are intolerant of or nonresponsive to nonopioid treatment,” the authors concluded. The study was published in Arthritis & Rheumatism (Arthritis Rheum. 2013;65[7];1795-1803). Anti-NGFs are monoclonal antibodies directed against nerve growth factor, which is associated with injury, inflammation, and chronic pain, according to the authors. Tanezumab is one of several anti-NGFs being studied for OA and other chronic pain conditions and is the furthest along in development. In 2010, the Food and Drug Administration (FDA) placed a partial hold on anti-NGF clinical trials after cases of osteonecrosis and avascular necrosis were reported in patients treated with tanezumab and in those treated with another anti-NGF. After an FDA advisory panel said that the anti-NGFs showed promise as analgesics, the clinical hold on tanezumab trials was lifted in August 2012, Dr. Brown's team noted. The development of the anti-NGFs “is an exciting potential addition to our present inadequate control of pain,” and research is resuming with a careful review of the risk of bone and joint changes, Dr. Roy Altman said in an interview. In his view, “the known risks would be acceptable to many people with poorly controlled pain.” Dr. Altman, professor of medicine, rheumatology, at the University of California, Los Angeles, was not an investigator in the study. The Pfizer study compared three tanezumab doses (2.5 mg, 5 mg, and 10 mg) administered intravenously at baseline, 8 weeks, and 16 weeks, with placebo, in 621 people with OA of the hip (mean age, 62-63 years) who could not or did not want to take nonopiate pain medications, did not get enough relief from these medications, or were candidates for hip surgery or other invasive treatments. Almost half were candidates for invasive treatment. At 16 weeks, tanezumab, at all three doses, “produced greater, clinically meaningful, and statistically significant improvements,” compared with placebo, in pain, physical function, and patient assessment of OA. Differences between placebo and treatment were greatest for the two higher doses. About two-thirds of the patients on treatment remained in the study through week 24 (considered the end of the study because of tanezumab's long half-life), compared with 38% of those on placebo. Overall, more patients on tanezumab reported adverse effects (55%-58% vs. 44% on placebo). Serious adverse events occurred in 3%-4.5% of patients in the treatment groups. The rate of total hip replacement was similar in the treatment and placebo groups, with a total of eight patients who had the operation (three in the placebo group, two each in the 2.5-mg and 5-mg groups, and one in the 10-mg group). These included two patients on tanezumab who had osteonecrosis thought to be related to tanezumab. The authors pointed out that an outside adjudication committee, however, did not confirm osteonecrosis in either of these patients and concluded that the reasons for joint replacements in the eight patients were inflammatory arthropathy, end-stage OA, rapidly progressive OA, or worsening OA. Dr. Altman said that he has consulted with Abbott and its now discontinued program on anti-NGF drugs.