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

Joanna Atkinson*, Roger A. Edwards, Gianluca Bonfanti, Joana Barroso, Thomas J. Schnitzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: We sought to predict analgesic response to daily oral nonsteroidal anti-inflammatory drugs (NSAIDs) or subcutaneous tanezumab 2.5 mg (every 8 weeks) at week 16 in patients with moderate-to-severe osteoarthritis, based on initial treatment response over 8 weeks. Methods: 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 week 16. Step 1 identified patients using a data-element combination method (based on pain score at baseline, pain score at week 8, pain score monotonicity at week 8, pain score path length at week 8, and body site [knee or hip]). Patients who could not be identified in step 1 were predicted in step 2 using a k-nearest neighbor method based on pain score and pain response level at week 8. Results: 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 ≥ 65 years relative to younger patients across most efficacy measure/response threshold combinations. Conclusions: 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 2.5 mg 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. ClinicalTrials.gov Identifiers: NCT02528188, NCT02709486, NCT02697773.

Original languageEnglish (US)
JournalAdvances in Therapy
DOIs
StateAccepted/In press - 2022

Keywords

  • k-Nearest neighbors
  • Nonsteroidal ant-inflammatory drugs
  • Osteoarthritis
  • Pain
  • Prediction
  • Tanezumab

ASJC Scopus subject areas

  • Pharmacology (medical)

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