Results from STEP 9 phase 3 clinical trial shows that studied semaglutide 2.4mg, compared to placebo as an adjunct to lifestyle modifications, reduces body weight and knee osteoarthritis-related pain in adults with obesity, and a clinical and radiologic diagnosis of moderate knee osteoarthritis, and pain that is at least moderately severe.
According to the trial, semaglutide met the study's primary endpoints and was superior to placebo in significantly reducing body weight and knee osteoarthritis-related pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. In addition, the trial met a key confirmatory secondary endpoint of improving patients' physical function.
STEP 9 was conducted over 68-weeks and was a double-blinded, randomised, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counselling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the WOMAC pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being).
In total, 407 patients with a mean baseline body weight of 239.5lbs were emrolled and semaglutide led to a –13.7% mean change from baseline in body weight at week 68 versus –3.2% with placebo (p<0.001). Participants also had pain due to knee osteoarthritis, with a WOMAC pain score ≥40 out of 100 at randomisation. Semaglutide also led to a mean change from baseline (70.9) in the WOMAC pain score of –41.7 at week 68 versus –27.5 with placebo (p<0.001). WOMAC is a 24-item patient-reported questionnaire that assesses clinically important symptoms of pain, stiffness, and physical function in patients with hip and/or knee osteoarthritis.
A greater improvement in physical functioning scores was also observed from baseline at week 68 among trial participants taking semaglutide versus placebo (mean change: 12.0 versus 6.5 points (<0.001]) as measured by the 36-Item Short Form Survey (SF-36v2).
"Obesity-related knee osteoarthritis is a progressive condition that can lead to pain and stiffness of the knee and impair critical daily functions such as walking or moving around. The risk of developing the condition is more than four times higher in people with obesity. Weight reduction along with physical activity is often a recommended approach to managing painful symptoms, but adherence can be challenging," said lead study author, Dr Henning Bliddal from the Parker Institute, Copenhagen University Hospital, Denmark. "There is a significant need for non-surgical and sustainable treatment options for those living with obesity-related osteoarthritis. The STEP 9 trial aimed to provide rigorous evidence as to how semaglutide may help these people."
The study implemented a targeted approach to safety data collection, with investigators recording only serious adverse events (SAEs), adverse events (AEs) leading to treatment discontinuation, AEs requiring invasive knee procedures, medication error, acute pancreatitis, COVID-19, and pregnancy or pregnancy-related AEs.1 AEs leading to treatment discontinuation occurred in 6.7% of patients in the semaglutide group and 3.0% of patients in the placebo group. The most common AEs leading to treatment discontinuation were gastrointestinal disorders (2.2% of patients in the semaglutide group and 0% of patients in the placebo group) and neoplasms (benign, malignant, and unspecified) (semaglutide, 1.9%; placebo, 1.5%). The incidence of SAEs was similar in both groups (semaglutide, 10.0%; placebo, 8.1%).
"Obesity is a complex metabolic disease associated with multiple co-morbid conditions, including knee osteoarthritis," said Dr Anna Windle, Senior Vice President, Clinical Development, Medical and Regulatory Affairs, Novo Nordisk. "The STEP 9 results are encouraging and provide important information about the effect of semaglutide, a glucagon-like peptide-1 receptor agonist, on knee osteoarthritis outcomes in people with obesity. We look forward to working with regulatory authorities on next steps based on these findings."
STEP 9 was funded by Novo Nordisk.
The findings were featured in the paper, ‘Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis’, published in the New England Journal of Medicine. To access this paper, please click here (log-in maybe required)
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