The findings are consistent with previous research about the efficacy of tanezumab for chronic low back pain.
John Markman, MD
Findings of new research suggest tanezumab provides relief in patients with chronic low back pain.
Lead study author John Markman, MD, and a team of investigators conducted the study in 191 sites across 8 countries in North America, Europe, and Asia. The study is the first to show long-term relief for chronic low back pain with a single dose of tanezumab delivered under the skin once every 2 months.
“This demonstration of efficacy is a major breakthrough in the global search to develop non-opioid treatments for chronic pain,” Markman, director of the Translational Pain Research Program at the University of Rochester Medical Center Department of Neurosurgery, said in a statement. “There were also improvements in function linked to the reduction in pain severity.”
In the randomized, double-blind, phase 3 study, Markman and colleagues assessed tanezumab in patients with chronic low back pain and a history of inadequate response to standard-of-care analgesics. Patients underwent a screening which included a washout period for prohibited medications and an initial pain assessment.
Individuals were eligible if they were >18 years old with axial predominant chronic low back pain of >3 months. Key criteria for inclusion were an average low back pain intensity score >5, Patient’s Global Assessment of Low Back Pain score of fair, poor, or very poor, and a history of inadequate response to >3 different categories of standard-of-care analgesics (acetaminophen/paracetamol, nonprescription NSAIDs, prescription NSAIDs, opioids, tapentadol, tricyclic antidepressants, benzodiazepines or muscle relaxants, lidocaine patch, and serotonin-norepinephrine reuptake inhibitors.
The study started with a 56-week double-blind treatment period followed by a 24-week safety follow-up. Patients were randomized 1:1:2:2:3 to placebo/subcutaneous tanezumab 5 mg (switch from placebo to tanezumab at week 16), placebo/subcutaneous tanezumab 10 mg (switch from placebo to tanezumab at week 16), subcutaneous tanezumab 5 mg, subcutaneous tanezumab 10 mg, or oral tramadol prolonged-release.
The oral tramadol tablet was given once daily with titration from 100 mg/day up to a maximum of 300 mg/day based on efficacy and tolerability over 4 weeks. Tanezumab was given in a prefilled syringe of 1 mL volume and was given subcutaneously in the abdomen or thigh by site staff every 8 weeks. Both subcutaneous and oral placebo were provided and administered the same as tanezumab and tramadol.
Before patients could get their third administration at week 16, they needed to demonstrate a >30% reduction from baseline in average lower back pain intensity and a >15% reduction from baseline in mean weekly lower back pain intensity at any week from 1-15 to continue the study. Prior to fifth administration at week 32, patients needed to demonstrate a >30% reduction from baseline in lower back pain intensity to continue.
The primary endpoint was change in lower back pain intensity from baseline to week 16 (tanezumab vs placebo). Additional endpoints included the percentage of patients with >50% reduction from baseline in in lower back pain intensity at week 16, change in the Roland Morris Disability Questionnaire from baseline to week 16, and change in lower back pain intensity from baseline to week 2.
In total, 6518 patients were screened, 1832 were randomized, and 1825 received >1 dose of subcutaneous medication. Nearly 65% of patients discontinued treatment by week 56, commonly due to inadequate efficacy. A majority of the patients (57%) were female and 72.4% were white with a mean age of 49 years old. Mean baseline lower back pain intensity and Roland Morris Disability Questionnaire scores were 7.2 and 15.
Tanezumab 10 mg met the primary endpoint. It significantly improved lower back pain intensity at week 16 versus placebo (least squares [LS] mean difference, -.4; 95% CI, -.76 to -.04; P=.0281). The therapy also significantly improved all key secondary endpoints.
Tanezumab 5 mg did not meet the primary endpoint LS mean treatment difference vs placebo, -.30; 95% CI, -.66 to .07; P=.1117). Due to the treatment not meeting the primary endpoint, it prevented formal testing of key secondary endpoints.
Overall, the proportion of patients with >50% improvement in lower back pain intensity at week 16 was 37.4% in the placebo group, 43.3% in the tanezumab 5 mg group (OR vs placebo, 1.28; 95% CI, .97-1.7; P=.0846), and 46.5% in the tanezumab 10 mg group (OR vs placebo, 1.45; 95% CI, 1.09-1.91; P=.0101). Joint safety events were more likely with tanezumab 10 mg (2.6%) than tanezumab 5 mg (1%), tramadol (.2%), or placebo (0%).
The study, “Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety,” was published online in the journal Pain.