Effects of pentosan polysulfate sodium on joint structure and function out to six months in naturally-occurring canine osteoarthritis.

Abstract

OBJECTIVE: To evaluate the durability of effect and disease modification potential of a six-week course of pentosan polysulfate sodium (PPS) therapy out to 26 weeks (six months) in companion dogs with naturally-occurring osteoarthritis. DESIGN: Twenty mixed-breed companion dogs were enrolled and randomized to receive either subcutaneous 3 mg/kg PPS injections (n = 14) or placebo (n = 6) once weekly for six weeks. Dogs underwent assessments for pain, functional gait analysis, MRI, and biomarker analysis at baseline and selected timepoints. RESULTS: PPS treatment was well tolerated throughout the study. At baseline, the PPS-treated group had higher pain with Helsinki Chronic Pain Index (HCPI) scores of 15.14 compared to 8.83 in placebo. PPS-treated dogs experienced sustained HCPI reductions compared to placebo at 26 weeks after adjusting for differences in baseline pain. The PPS-treated group experienced normalization of gait symmetry up to week 26, indicating a reduction in lameness and an improvement in overall function. Total cartilage volume increased at weeks 8 and 26 from baseline in the PPS-treated group compared to placebo, and OA disease progression biomarker changes (CTX-I, HA, and TIMP-1) were consistent with slowed cartilage degradation at weeks 8 and 26. CONCLUSIONS: PPS-treated dogs experienced improvements in pain, joint function, and cartilage volume compared to placebo, supported by changes in biomarkers at weeks 8 and 26. The 26-week timepoint in this translational canine model provides insights into the potential disease-modifying mechanisms and durability of PPS in long-term treatment outcomes in humans with OA.