Peter Ghosh1, Jack Edelman2, Lyn March1, Margaret Smith1. 1. Institute of Bone and Joint Research, University of Sydney, Royal North Shore Hospital of Sydney, St. Leonards, Australia. 2. Queen Elizabeth II Medical Centre, Perth, Australia.
Abstract
BACKGROUND: Recent recommendations from the Group for the Respect of Excellence and Ethics in Science for the clinical assessment of the effects of disease-modifying osteoarthritis (OA) drugs suggest that improvement in joint space narrowing, pain, and function relative to a control group should be the primary end points. OBJECTIVE: The aim of this study was to assess the ability of sodium pentosan polysulfate (NaPPS) to improve pain and function in patients with OA of the knee. METHODS: This randomized, double-blind, placebo-controlled pilot study was performed at the Queen Elizabeth II Medical Centre, Perth, Australia. Patients aged ≥18 years with OA of the knee were randomly assigned to receive NaPPS 3 mg/kg or Ringer's solution (control), IM QW for 4 weeks. Efficacy was assessed at enrollment and weekly during the 4 weeks of treatment and at weeks 8, 12, 16, and 24. Seven direct clinical assessments were made, including intensity of early morning joint stiffness, pain at rest, and pain on walking. A 10-cm visual analog scale (VAS) was used to assess pain at rest and on walking and early morning joint stiffness. Response was defined as a change from baseline in VAS score ≥2 cm. Function was assessed using the 10-cm VAS to rate 13 activities of daily living (ADLs), including stair climbing and domestic chores. Patient global assessment of the overall effectiveness of the study drug comprised a 4-point Likert scale (0 = not effective to 3 = maximally effective). An aggregate score for all ADL functions was calculated as the mean change from baseline score of all of the ADLs as determined at 4, 8, 12, 16, and 24 weeks after commencement of the study. For tolerability monitoring, hematology and biochemistry were used, and patients were questioned about adverse events at each visit. RESULTS: A total of 114 patients were enrolled (83 women, 31 men; mean [SD] age, 63.3 [1.5] years; NaPPS group, 54 patients; control group, 60 patients). Significant differences in scores of 3 of the 7 direct clinical assessments were found between the 2 groups (duration of joint stiffness at 4, 8, 12, and 16 weeks [all, P:5 0.015]; pain at rest at 8, 12, 16, and 24 weeks [all, P ≤ 0.017]; and patient global assessment at 4, 8, 12, 16, and 24 weeks [all, P <- 0.006]). The rates of trial continuation were higher in the NaPPS group compared with those in the control group at 8, 12, and 24 weeks (all, P < 0.05). Mean scores for 3 of 13 ADLs were significantly higher in the NaPPS group compared with those in the control group at weeks 8 and 12 (all, P ≤ 0.03). On combining all of the ADL scores, functional improvement from baseline was found at weeks 8 and 12 in the NaPPS group (both, P = 0.02). Mild bruising at the injection site occurred in <1% of patients in both treatment groups. CONCLUSIONS: In this pilot study, 4 weekly injections of NaPPS were associated with significantly improved duration of joint stiffness and pain at rest compared with controls for 20 weeks after the cessation of treatment, and significantly improved pain on walking and overall function for 8 weeks after the cessation of treatment in these patients with OA of the knee.
RCT Entities:
BACKGROUND: Recent recommendations from the Group for the Respect of Excellence and Ethics in Science for the clinical assessment of the effects of disease-modifying osteoarthritis (OA) drugs suggest that improvement in joint space narrowing, pain, and function relative to a control group should be the primary end points. OBJECTIVE: The aim of this study was to assess the ability of sodium pentosan polysulfate (NaPPS) to improve pain and function in patients with OA of the knee. METHODS: This randomized, double-blind, placebo-controlled pilot study was performed at the Queen Elizabeth II Medical Centre, Perth, Australia. Patients aged ≥18 years with OA of the knee were randomly assigned to receive NaPPS 3 mg/kg or Ringer's solution (control), IM QW for 4 weeks. Efficacy was assessed at enrollment and weekly during the 4 weeks of treatment and at weeks 8, 12, 16, and 24. Seven direct clinical assessments were made, including intensity of early morning joint stiffness, pain at rest, and pain on walking. A 10-cm visual analog scale (VAS) was used to assess pain at rest and on walking and early morning joint stiffness. Response was defined as a change from baseline in VAS score ≥2 cm. Function was assessed using the 10-cm VAS to rate 13 activities of daily living (ADLs), including stair climbing and domestic chores. Patient global assessment of the overall effectiveness of the study drug comprised a 4-point Likert scale (0 = not effective to 3 = maximally effective). An aggregate score for all ADL functions was calculated as the mean change from baseline score of all of the ADLs as determined at 4, 8, 12, 16, and 24 weeks after commencement of the study. For tolerability monitoring, hematology and biochemistry were used, and patients were questioned about adverse events at each visit. RESULTS: A total of 114 patients were enrolled (83 women, 31 men; mean [SD] age, 63.3 [1.5] years; NaPPS group, 54 patients; control group, 60 patients). Significant differences in scores of 3 of the 7 direct clinical assessments were found between the 2 groups (duration of joint stiffness at 4, 8, 12, and 16 weeks [all, P:5 0.015]; pain at rest at 8, 12, 16, and 24 weeks [all, P ≤ 0.017]; and patient global assessment at 4, 8, 12, 16, and 24 weeks [all, P <- 0.006]). The rates of trial continuation were higher in the NaPPS group compared with those in the control group at 8, 12, and 24 weeks (all, P < 0.05). Mean scores for 3 of 13 ADLs were significantly higher in the NaPPS group compared with those in the control group at weeks 8 and 12 (all, P ≤ 0.03). On combining all of the ADL scores, functional improvement from baseline was found at weeks 8 and 12 in the NaPPS group (both, P = 0.02). Mild bruising at the injection site occurred in <1% of patients in both treatment groups. CONCLUSIONS: In this pilot study, 4 weekly injections of NaPPS were associated with significantly improved duration of joint stiffness and pain at rest compared with controls for 20 weeks after the cessation of treatment, and significantly improved pain on walking and overall function for 8 weeks after the cessation of treatment in these patients with OA of the knee.
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