Higher doses of tanezumab linked to abnormal peripheral sensation vs. NSAIDs in OA
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Among patients with osteoarthritis, increased tanezumab doses are associated with a higher incidence of abnormal peripheral sensation compared with NSAIDs, according to a speaker at the 2020 American Neurological Association Annual Meeting.
“Tanezumab is a monoclonal antibody against nerve growth factor that is in development for the treatment of chronic pain in patients with osteoarthritis,” Mark T. Brown, MD, of Pfizer, told Healio Rheumatology.
To examine the long-term neurological safety of subcutaneous tanezumab (Pfizer, Eli Lilly & Co.), compared with NSAIDs, among patients with OA, Brown and colleagues studied 2,996 participants with moderate-to-severe hip or knee OA pain and functional disability. In addition, all participants were required to have a history of inadequate pain relief with acetaminophen, inadequate pain relief with or intolerance to tramadol or opioids, or an unwillingness to use opioids. Participants were receiving stable doses of NSAIDs prior to enrollment, as well as during a screening period of 37 days or less.
In the study, patients were randomized to receive either double-dummy tanezumab — 2.5 mg or 5 mg every 8 weeks — or NSAIDs twice daily for 56-weeks. The follow-up period was 24 weeks. The researchers assessed neurological safety with peripheral and sympathetic adverse events, neurologic examinations, orthostatic blood pressure, electrocardiograms and protocol-specified neurologic consultations using blinded, external neurologist diagnostic reviews.
According to the researchers, the incidence of abnormal peripheral sensation was 6.2% in the 2.5 mg tanezumab group, 9% in the 5 mg group, and 4.6% among those who received NSAIDs. Hypoesthesia, paresthesia and carpal tunnel syndrome were the most commonly reported examples. Clinically significant worsening on examination occurred in less than 1% of any treatment group at the time of last assessment.
Diagnoses following external neurological consultation included mononeuropathy — seen in 1.3%, 2.1% and 1% in the 2.5 mg and 5 mg tanezumab arms and NSAID group, respectively — radiculopathy — 0.9%, 0.4% and 0.5%, respectively — and polyneuropathy — 0.3%, 0.5% and 0%, respectively. The incidence of possible sympathetic function, including bradycardia, syncope, orthostatic hypotension, anhidrosis and hypohidrosis, was 1.8% in the 2.5 mg tanezumab group, 2.3% in the 5 mg group and 2.9% among those treated with NSAIDs. No participants were diagnosed with sympathetic neuropathy.
“Results from this study added to the body of safety data for tanezumab and confirmed the neurologic safety findings observed in other clinical trials, including placebo-controlled studies,” Brown said. “Overall, adverse events of abnormal peripheral sensation were generally mild-to-moderate in severity, generally resolved during the study and infrequently led to study discontinuation. The results of blinded external neurologic review of consultation data did not indicate that tanezumab was associated with peripheral polyneuropathy.”
“Sympathetic function adverse events were balanced across the treatment groups, none of the patients were diagnosed with sympathetic neuropathy and there was no evidence of an effect of tanezumab on sympathetic nervous system function,” he added. “These findings were clinically significant since in this large, randomized, double-blind, NSAID-controlled study, they demonstrated the long-term peripheral and sympathetic nervous system safety profile of tanezumab, a potentially first-in-class anti-NGF treatment for patients with chronic osteoarthritis pain.”
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Sandroni P. Subcutaneous tanezumab versus NSAID for the treatment of osteoarthritis: Neurological safety in a randomized, double-blind, active-controlled, 80-week phase 3 study. Presented at: American Neurological Association Annual Meeting; October 4-9, 2020 (virtual meeting).
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