Study of Tanezumab for Chronic Low Back Pain
Chronic low back pain remains a problem without a good solution. No single type of treatment works for everyone. Most patients end up combining multiple different treatments until they find the right mix that is effective for them. This may include medications, counseling or behavioral therapy, physical therapy, and surgery.

Medications often include pain relievers (analgesics) such as tylenol and antiinflammatories such as ibuprofen, naproxen, or other prescription nonsteroidal antiinflammatories (NSAIDs). Sometimes mild narcotics such as codeine or tramadol are prescribed.

A new drug called Tanezumab developed as a treatment for pain has been shown effective in patients with osteoarthritis, interstitial cystitis (bladder pain), and bone pain from cancer. Tanezumab is a monoclonal antibody (mAb) that works to alleviate pain because it neutralizes nerve growth factor (NGF). Nerve growth factor sets up pain signals and even heightens the body's responsiveness to painful stimuli. This means the nervous system responds faster to smaller inputs creating larger pain responses.

Tanezumab stops nerve growth factor activity. Tanezumab was undergoing Phase II and III clinical trials for the treatment of various pain problems, including chronic low back pain, bone cancer pain, and interstitial cystitis. But studies were halted in June 2010 when some patients with osteoarthritis got much worse after taking tanezumab and ended up needing hip replacements.

The reports included 16 patients who had X-ray evidence of bone necrosis (bone death) that required total joint replacement. It is possible that joint failure occurred as a result of excess wear and tear on the joint when pain was absent. In a sense, tanezumab as a pain reliever may have been too effective for these patients with painful hip and knee osteoarthritis. Eliminating the pain did not stop the degenerative processes and the increased activity further damaged the involved joints.

So for the moment, tanezumab is on regulatory hold due to the adverse effects in osteoarthritis patients. In the meantime, the results of this study comparing tanezumab with naproxen and placebo for chronic low back pain (conducted before the hold) are reported.

Over 200 patients with chronic low back pain caused by osteoarthritis were included in the study. They were randomly divided into three groups. Group one received a single intravenous dose of (real) tanezumab and a placebo (sugar pill) naproxen (antiinflammatory). Group two were given an intravenous tanezumab placebo with real naproxen. Group three received placebo tanezumab and placebo naproxen. Group one was labeled the tanezumab group. Group two was the naproxen group. And group three was the placebo group.

The patients each kept a daily electronic diary recording pain levels and the use of any "rescue" medication. Rescue medication refers to any pain reliever used when painful symptoms were intolerable. Pain intensity and rescue meds were two of the measures used before and after to compare results. Questionnaires were also used to measure function and disability.

The effectiveness of tanezumab for chronic low back pain was measured using these outcomes. Safety was also a concern and was assessed by reviewing adverse effects reported by the patients. Review and analysis of the data showed that everyone in all three groups had measurable pain relief. The tanezumab group had the best results, naproxen second best results, and placebo ranked third after the other two.

These were the results during the early weeks (zero up to six weeks). After eight weeks, the naproxen and placebo groups were equal. The tanezumab group continued to report the best results throughout the 12 week treatment period. That answers the question of efficacy or effectiveness -- tanezumab clearly outperformed the other two (naproxen and placebo).

What about safety? What were the side effects (if any) in the tanezumab group and how did they compare to the other two groups? There were reactions in all three groups but the tanezumab-treated group did have the highest incidence of problems. Joint pain, headaches, muscle pain, and painful responses to stimuli (e.g., touch) that shouldn't be perceived as painful were reported in the tanezumab group. These side effects were temporary and all gone by the end of the study.

No one in any of the groups had serious complications (i.e., permanent paralysis or death). Overall, tanezumab provided better pain relief and resulted in better function than either naproxen or placebo. Adverse side effects of the tanezumab were mild-to-moderate and temporary.

Long-term studies are needed to see if recurrence of back pain (common among back pain sufferers) can be changed with tanezumab and if there are any long-term side effects such as bone necrosis. The possibility of having an effective nonnarcotic medication for patients with chronic low back pain that has been unresolved with other treatments is worth pursuing.

The authors suggest resuming studies of this medication for chronic low back pain if/when the ban on its use in studies is lifted. There is enough evidence from this study (and other studies) that the use of tanezumab is safe and effective with chronic low back pain patients.
Nathaniel Katz, et al. Efficacy and Safety of Tanezumab in the Treatment of Chronic Low Back Pain. In PAIN. October 2011. Vol. 152. No. 10. Pp. 2248-2258.