medwireNews: Findings from a phase 2a proof-of-concept study suggest that the granulocyte–macrophage colony-stimulating factor (GM-CSF) otilimab may deserve further investigation for inflammatory hand osteoarthritis (OA).
There was some evidence of an improvement in pain among the 22 participants randomly assigned to receive otilimab compared with the 22 given placebo, despite no significant between-group difference in the primary endpoint of change in hand pain from baseline to week 6, say the investigators.
They report in The Lancet Rheumatology that the least-squares mean (LSM) decrease in 24-hour average hand pain on a 0–10-point numeric rating scale (NRS), averaged over 7 days, from baseline to week 6 was 1.70 points in the otilimab arm and 1.34 points in the placebo arm, giving a nonsignificant between-group difference of 0.36 points.
All participants had inflammatory hand OA despite treatment with at least one course of nonsteroidal anti-inflammatory drugs, and otilimab was administered subcutaneously at a dose of 180 mg/week from weeks 0–4, followed by 180 mg every other week until week 10.
Although the primary outcome was not met, Paul Tak (University of Amsterdam, the Netherlands) and colleagues say that otilimab-treated patients experienced “consistent improvements in the reduction of pain and functional impairment” relative to those given placebo.
For instance, individuals in the otilimab group had a 1.01-point greater reduction in 24-hour worst hand pain on the NRS from baseline to week 12 than those given placebo, rising to a 1.11-point reduction, albeit still nonsignificant, when the analysis was restricted to the 39 participants who received all eight doses of the study drug.
And analysis of Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, functional impairment, and stiffness scores showed a similar pattern, with numerically, but not significantly, greater improvements in the otilimab group, they add.
Tak and team highlight that otilimab dosing was “suboptimal” in their study, with “lower than anticipated” serum concentrations based on previous studies. They also caution that their trial was limited by small patient numbers and a short duration of follow-up.
Nevertheless, they believe that the nonsignificant trends toward improvements in pain and physical function with otilimab “support a role for GM-CSF in the signs and symptoms of hand osteoarthritis and provide a basis for further clinical development.”
They also point to a phase 2b trial of otilimab in patients with rheumatoid arthritis, reported previously by medwireNews, which demonstrated significant reductions in patient-reported pain and disease activity with the GM-CSF inhibitor versus placebo.
The researchers say that “[t]here were no unexpected safety findings” in their OA trial, with “no evidence” that otilimab treatment increased the risk for serious infections, and “no treatment-related serious adverse events were reported.”
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