Oral Calcitonin Found Beneficial in Knee Osteoarthritis

Abstract

SAN DIEGO – Oral salmon calcitonin significantly reduced pain and stiffness, improved physical function, and slowed cartilage loss, especially in the medial tibial compartment in a 2-year, placebocontrolled, phase III clinical trial involving 1,169 elderly patients with painful knee osteoarthritis. Even though the trial did not show improvement in joint space, it suggests that oral salmon calcitonin dosed at 0.8 mg twice daily for 24 months “is safe and has sustained symptommodifying” benefits in osteoarthritis, said Dr. Morten Karsdal, CEO of Nordic Bioscience in Herlev, Denmark, which sponsored the trial and is developing the drug in collaboration with Novartis Pharma. At month 24, 17% of the 585 subjects had circulating antibodies against the oral calcitonin (oCT). Historically, 40%70% of users develop antibodies against nasal and injectable formulations, Dr. Karsdal said in his report at the World Congress on Osteoarthritis. “It's potentially a really important piece of work,” said rheumatologist and epidemiologist David Hunter, a professor of medicine at the University of Sydney in Australia. “Right now, we don't have any disease modifying agents” for osteoarthritis. “People took oral calcitonin for 2 years. That's something that couldn't be done with a nasal product” because many people develop allergies to the nasal product, he said. Overall, “they hit the end points for pain and function. What the clinical relevance of those effects are it's difficult to know,” said Dr. Hunter. He added that he expects that regulatory approval of the drug for arthritis is going to be a hard sell because the drug didn't improve joint space, a common endpoint in drug-approval trials in several countries. The mean age of trial subjects was 64 years, and mean body mass index about 29 kg/m2; 68% were women. Most patients had Kellgren-Lawrence grade II disease, the rest were grade III. Rescue medication was allowed in both the placebo and treatment arms. By month 24, oCT subjects demonstrated about a 5% loss in cartilage volume on MRI in both the signal and non-signal knee; placebo subjects demonstrated slightly more than a 7% loss in both knees. The differences were statistically significant. “We prevent a decrease; we do not gain cartilage,” Dr. Karsdal said. Also at month 24, oCT bested placebo in WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain scores (-115.7 vs. –94.9 mm; P = .002), function scores (-338.7 vs. –283.0 mm; P = .013), and stiffness scores (-44.1 vs. –32.6 mm; P less than .001). Oral calcitonin also beat placebo on 24-hour visual analog scale (VAS) pain scores (P = .018), patient global assessment (P = .008), and physician global assessment (P = .014). The most common adverse events in the oCT group vs. placebo were hot flashes (18% vs. 4%), nausea (14% vs. 3%), dyspepsia (10% vs. 5%), and diarrhea (10% vs. 4%). Almost 20% of oCT subjects dropped out of the trial because of those and other side effects. The figure for the control group was 6%. The side effects “are associated with the mode of action of salmon calcitonin, and mostly happened early,” Dr. Karsdal said. Dr. Hunter said he has no conflict of interest.