Subcutaneous tanezumab, NSAIDs improve osteoarthritis pain
Click Here to Manage Email Alerts
Tanezumab and NSAIDs both demonstrated early and sustained improvement in pain and function among patients with knee or hip osteoarthritis, according to data published in Arthritis Research and Therapy.
“A combination of pharmacological, physical, and behavioral approaches is recommended for the management of OA, though recent guidelines highlight the need for new treatment options,” Tuhina Neogi, MD, PhD, of the Boston University School of Medicine, and colleagues wrote.
“The cornerstone of pharmacologic treatment is nonsteroidal anti-inflammatory drugs (NSAIDs), which demonstrate efficacy for OA-related pain in short-term clinical trials and are typically recommended over other pharmacological agents,” they added. “However, due to the potential for gastrointestinal, cardiovascular, and renal complications, their use is not recommended in patients at risk for these adverse events (AEs) and their long-term use is not recommended in any patient.”
To study the safety and efficacy of subcutaneous tanezumab (Eli Lilly, Pfizer), a monoclonal antibody that targets nerve growth factor, in patients with knee or hip OA, Neogi and colleagues conducted a phase 3, double-blind, double-dummy, active-controlled, parallel-group study. The trial was conducted at 446 sites throughout the United States, Europe, Latin America and the Asia-Pacific regions between June 2015 and February 2019. In addition, it employed a screening period of up to 37 days, a 56-week double-blind treatment period and a 24-week follow-up period to investigate safety.
Participants were required to be aged 18 years or older, meet the American College of Rheumatology classification criteria for hip or knee OA, and demonstrate a Kellgren-Lawrence grade of two or higher in index joint, WOMAC pain and WOMAC physical scores of five or greater and a PGA-OA rating of “fair, poor, or very poor” at baseline. Patients were randomized to receive either tanezumab 2.5 mg plus oral placebo, tanezumab 5 mg plus oral placebo, or an oral NSAID. Treatment was administered by site staff every 8 weeks for roughly 56 weeks.
Participants also self-administered oral study medication, the researchers wrote. Patients only continued to receive subcutaneous tanezumab after week 16 if they met certain predefined criteria, including a 15% or greater reduction in WOMAC pain scores from baseline to weeks 2, 4 or 8, and a 30% or greater reduction in the score at week 16.
In addition to efficacy monitoring, researchers conducted musculoskeletal and neurological examinations throughout the length of the study.
Overall, 2,996 patients received one or more dose of study medication. Among those, 1,807 participants received subcutaneous tanezumab through week 16 and 1,312 completed the full 56-week treatment period. Out of the patients who completed the 56-week period, 1,222 completed the safety follow-up period of 24 weeks.
According to the researchers, improvements in average pain and the index joint over the treatment period were greater in patients receiving tanezumab at certain baselines — weeks 3 to 20 in tanezumab 2.5 mg, and weeks 4 to 24 for tanezumab 5 mg — than in patients receiving an NSAID (P .05). Across every included group, the proportion of patients who saw “moderate” improvement in the WOMAC pain score was 68.9% to 72.9% at week 16, and 51.2% to 53.1% at week 56, the researchers wrote.
For patients achieving “substantial” improvement in the metric, the proportions were 51.5% to 56.5% at week 16, and 41.5% to 44.3% at week 56, they added.
Regarding safety, the most adverse events or discontinuations occurred in the group receiving tanezumab 5 mg, with 67.1% of patients experiencing an adverse event, 8% experiencing a serious adverse event and 8.8% discontinuing therapy. The rate of adverse events and discontinuations was similar in the tanezumab 2.5 mg and NSAID groups.
“This study is the longest assessment of tanezumab in participants with OA to date (56-week treatment and 24-week safety follow-up), which is notable since long-term trial data on OA treatments, including NSAIDs, is generally lacking,” Neogi and colleagues wrote. “Though tanezumab was well-tolerated in most participants, dose-dependent joint safety events occurred more frequently with tanezumab than with NSAID and should be taken into account when assessing tanezumab’s overall risk/benefit profile.”
Collapse
Read more about
Click Here to Manage Email Alerts