A Two-Step, Trajectory-Focused, Analytics Approach to Attempt Prediction of Analgesic Response in Patients with Moderate-to-Severe Osteoarthritis.

Abstract

We sought to predict analgesic response to daily oral nonsteroidal anti-inflammatory drugs (NSAIDs) or subcutaneous tanezumab 2.5mg (every 8weeks) at week16 in patients with moderate-to-severe osteoarthritis, based on initial treatment response over 8weeks. Data were derived from three randomized controlled trials of osteoarthritis. A two-step, trajectory-focused, analytics approach was used to predict patients as responders or non-responders at week16. Step1 identified patients using a data-element combination method (based on pain score at baseline, pain score at week8, pain score monotonicity at week8, pain score path length at week8, and body site [knee or hip]). Patients who could not be identified in step1 were predicted in step2 using a k-nearest neighbor method based on pain score and pain response level at week8. Our approach predicted response with high accuracy in NSAID-treated (83.2-90.2%, n = 931) and tanezumab-treated (84.6-91.0%, n = 1430) patients regardless of the efficacy measure used to assess pain, or the threshold used to define response (20%, 30%, or 50% improvement from baseline). Accuracy remained high using 50% or 20% response thresholds, with 50% and 20% yielding generally slightly better negative and positive predictive value, respectively, relative to 30%. Accuracy was slightly better in patients aged ≥ 65years relative to younger patients across most efficacy measure/response threshold combinations. Analyzing initial 8-week analgesic responses using a two-step, trajectory-based approach can predict future response in patients with moderate-to-severe osteoarthritis treated with NSAIDs or 2.5mg tanezumab. These findings demonstrate that prediction of treatment response based on a single dose of a novel therapeutic is possible and that predicting future outcomes based on initial response offers a way to potentially advance the approach to clinical management of patients with osteoarthritis. NCT02528188, NCT02709486, NCT02697773.