Tanezumab Has Small Effect on Difficult-to-Treat Chronic Low-Back Pain, May Cause Joint Problems in Some

By Will Boggs MD

July 01, 2020

NEW YORK (Reuters Health) - Tanezumab produces a small reduction in pain and improves function in patients with chronic low-back pain not adequately controlled by standard-of-care analgesics, according to results from a phase-3 study.

It is also associated with joint problems, however, including some that required joint replacement, researchers report in Pain

"This drug works in a whole new way by blocking a protein that makes nerves more sensitive in people who suffer from chronic low-back pain," Dr. John D. Markman of the University of Rochester Medical Center, in Rochester, New York, told Reuters Health by email.

Tanezumab is a monoclonal antibody that blocks nerve growth factor (NGF), which is thought to play an important role in the pathogenesis of chronic low-back pain. Previous phase-2 studies have demonstrated its efficacy for reducing pain associated with osteoarthritis and nonradicular chronic low-back pain.

In the current study, Dr. Markman and colleagues evaluated the efficacy and safety of subcutaneous tanezumab (5 or 10 mg every eight weeks) or oral tramadol prolonged-release (100-300 mg/day) versus placebo in their 80-week study of 1,825 patients with chronic low back pain.

"The patients enrolled in this study were those with low-back pain that is long lasting and difficult to treat," Dr. Markman said. "They had to have tried three other medications without success."

Tanezumab 10 mg met the primary endpoint by providing significantly greater improvement in low back pain intensity (LBPI) at week 16 by a mean 0.40 point (on a scale from 0 = no pain to 10 = worst possible pain) more than placebo.

Improvements in LBPI did not differ significantly between tanezumab 5 mg and placebo.

Significantly more patients taking tanezumab 10 mg (46.3%) than taking placebo (37.4%) achieved at least a 50% improvement in LBPI at week 16, but there was no difference between the tanezumab 5 mg and placebo groups.

Patients in the tanezumab 10 mg group experienced significantly greater improvements in Roland Morris Disability Questionnaire (RMDQ) scores at week 16, averaging 1.74 points (on a scale from 0 = no disability to 24 = severe disability) better than placebo. RMDQ scores at week 16 did not differ between the tanezumab 5 mg and placebo groups.

LBPI scores at week 16 did not differ significantly between the tanezumab 5 mg or 10 mg groups and the tramadol group, but both doses of tanezumab improved RMDQ scores compared with tramadol.

Serious adverse events through week 56 were more common in the tanezumab 10 mg group (4.6%) than in the tramadol group (3.2%), largely as a result of musculoskeletal and connective tissue events.

Overall, 30 patients had safety events involving the joints, including nine in the tanezumab 5 mg group, 17 in the tanezumab 10 mg group, four in the tramadol group, and none in the placebo group. Seven patients required a total joint replacement, all in the tanezumab 10 mg group (1.4%).

The most common joint safety event was rapidly progressive osteoarthritis, which occurred in five tanezumab 5 mg patients, nine tanezumab 10 mg patients and one tramadol patient.

"This was a very long study that aimed to understand the risk of a rare joint problem that led to joint replacement in a few patients," Dr. Markman said. "Clinicians are going to need to learn how to screen and monitor patients for specific risks just as they do when prescribing an anti-inflammatory or recommending surgery for chronic low-back pain."

"For patients who do not want to take an opioid type medication or cannot take an anti-inflammatory like ibuprofen and also do not want undergo surgery, this may be an option to consider with their doctor someday in the future," he concluded.

Pfizer Inc. and Eli Lilly and Company funded the study, employed five of the authors and had various relationships with several others, including Dr. Markman.

SOURCE: https://bit.ly/3dvm7rN Pain, online May 19, 2020.

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