Clinically meaningful effect of strontium ranelate on symptoms in knee osteoarthritis: a responder analysis.
Bruyère O., Reginster JY., Bellamy N., Chapurlat R., Richette P., Cooper C.
The aim of this study was to assess the efficacy of strontium ranelate in improving symptoms in knee OA.Symptoms were assessed over 3 years in patients with primary knee OA receiving strontium ranelate 2 g/day (n = 454), 1 g/day (n = 445) or placebo (n = 472) in the Strontium Ranelate Efficacy in Knee Osteoarthritis Trial. Clinical response was evaluated using WOMAC subscores, minimal perceptible clinical improvement (MPCI), minimal clinically important improvement (MCII) and a modified OMERACT-Osteoarthritis Research Society International (OARSI) responder definition. Patients who withdrew prematurely from the study were considered non-responders.There was no significant effect on symptoms for strontium ranelate 1 g/day. At the dosage of 2 g/day, strontium ranelate was associated with greater response than placebo in terms of ≥20% improvement in WOMAC pain from baseline to the last visit (58% vs 47%, P = 0.002) and ≥50% improvement in WOMAC pain (42% vs 36%, P = 0.083). Significant differences were found in MPCI response for WOMAC pain (52% vs 40%, P < 0.001), stiffness (47% vs 39%, P = 0.009) and physical function (46% vs 37%, P = 0.009) and in MCII response for WOMAC physical function (46% vs 37%, P = 0.013). There were also more OMERACT-OARSI-like responders with strontium ranelate (44% vs 35%, P = 0.004). The treatment-placebo difference in MPCI response for WOMAC pain was significant after 6 months (P = 0.024), while that in MPCI and MCII response for WOMAC physical function reached significance after 12 months (P = 0.027 and P = 0.019, respectively).Treatment with strontium ranelate 2 g/day over 3 years is associated with a clinically meaningful improvement in pain from 6 months as well as physical function and stiffness as assessed by the number of responders above thresholds of clinical relevance.Current Controlled Trials. http://www.controlled-trials.com/ (ISRCTN41323372).