medwireNews: The anti‐nerve growth factor monoclonal antibody fasinumab improves pain and function in patients with knee or hip osteoarthritis (OA) who have a history of inadequate response or intolerance to analgesics, study findings indicate.
Furthermore, the effect sizes for some of the doses tested were “substantially greater than those reported with acetaminophen, opioids, and some NSAIDs [nonsteroidal anti-inflammatory drugs],” Gregory Geba (Regeneron Pharmaceuticals, Tarrytown, New York, USA) and co-authors report in Arthritis & Rheumatology.
For the double-blind phase IIb/III trial, patients with moderate‐to‐severe OA pain in the knee or hip and history of inadequate response or intolerance to analgesics including NSAIDs, acetaminophen, or opioids were randomly assigned to receive subcutaneous fasinumab 1 mg (n=85), 3 mg (n=84), 6 mg (n=85), 9 mg (n=83), or placebo (n=82) every 4 weeks for 16 weeks and then followed-up until week 36.
At baseline, mean WOMAC pain subscale scores ranged from 6.1 to 6.5 points across all five groups. Reductions in pain scores were apparent by week 2 in all groups and were maintained until week 16, at which point they were between 2.7 and 3.9 points.
The researchers found that all four doses of fasinumab showed “statistically significant and clinically important” greater reductions in the pain score compared with placebo, with least squares mean differences of 1.1, 1.1, 0.8, and 1.4 points in the 1, 3, 6, and 9 mg groups, respectively.
And they note that the lack of an “obvious dose-response relationship suggests having met or exceeded the threshold for maximal response.”
The reductions in pain corresponded to significantly greater improvements in physical function with all four doses of fasinumab relative to placebo at week 16.
Furthermore, greater proportions of patients receiving fasinumab versus placebo demonstrated substantial treatment effects, defined as at least a 30% improvement from baseline to week 16, in pain (63.5–73.8 vs 47.0%) and physical function (61.2–71.4 vs 44.6%) scores.
In spite of this, both outcomes worsened between weeks 16 and 36 in all five groups, albeit to levels below those at baseline.
During the treatment period, 62.0% of patients who received fasinumab at any dose and 54.9% of those who received placebo experienced at least one treatment-emergent adverse event (AE), most commonly infections (21.4 vs 15.9%) and musculoskeletal and connective tissue disorders (18.7 vs 17.1%).
Among the AEs of special interest, there were 25 arthropathies overall that occurred in a dose‐dependent manner, with one case in the placebo group and two, four, six, and 12 cases in the 1, 3, 6, and 9 mg fasinumab groups, respectively. The majority (64%) of these cases were discovered during scheduled radiographs and were not prompted by symptoms. One patient experienced destructive arthropathy at a fasinumab dose of 6 mg and there were no cases of sympathetic nervous system dysfunction.
Geba and team conclude: “The observation that efficacy at lower doses was similar to that of higher doses, but with lower rates of arthropathy, demands that future studies explore the benefit-risk at these lower doses.”
By Laura Cowen
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