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

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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.

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Notes

  1. © 1996 Nicholas Bellamy. WOMAC® is a registered trademark of Nicholas Bellamy (CDN, EU, USA).

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Acknowledgements

We thank the participants of the studies.

Funding

This study was funded by Pfizer and Eli Lilly and Company. The journal’s Rapid Service fee was funded by Pfizer and Eli Lilly and Company.

Medical Writing/Editorial Assistance

Medical writing support was provided by Matt Soulsby, PhD, CMPP, of Engage Scientific Solutions and was funded by Pfizer and Eli Lilly and Company.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

All authors contributed to the (1) conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version to be submitted.

Disclosure

Joanna Atkinson is a full-time employee of Pfizer, LTD. Roger A. Edwards is an owner of Health Services Consulting Corporation, a paid consultant by Pfizer in connection with this study and development of the manuscript. Gianluca Bonfanti is an employee of Engineering Ingegneria Informatica, a paid sub-contractor to Health Services Consulting Corporation in conjunction with this study and development of this manuscript. Joana Barroso has received research support from Grünenthal. Thomas J. Schnitzer reports clinical research study support from Pfizer, Lilly, Regeneron, Galapagos, Taiwan Liposome Corporation, and Anika Therapeutics and has served as a consultant or on an advisory board for Pfizer, Eli Lilly and Company, Glaxo-Smith Kline, AstraZeneca, Noven, Galapagos, and Merck.

Compliance with Ethics Guidelines

The studies included in this analysis were approved by an institutional review board or independent ethics committee at each study center. All patients provided written informed consent before participating. The studies were conducted in compliance with the Declaration of Helsinki and all International Conference on Harmonization Good Clinical Practice guidelines. Please see the primary study publications for more detail.

Data Sharing Statement

Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-studys/study-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the USA and/or EU or (2) in programs that have been terminated (i.e., development for all indications has been discontinued). Pfizer and Lilly will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer studies 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.

Author information

Authors and Affiliations

  1. Pfizer, LTD, Dorking Road, Tadworth, Surrey, KT20 7NS, England, UK

    Joanna Atkinson

  2. Health Services Consulting Corporation, Boxborough, MA, USA

    Roger A. Edwards

  3. Engineering Ingegneria Informatica, SPA, Milan, Italy

    Gianluca Bonfanti

  4. Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Joana Barroso & Thomas J. Schnitzer

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  1. Joanna Atkinson
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  2. Roger A. Edwards
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  3. Gianluca Bonfanti
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  5. Thomas J. Schnitzer
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Corresponding author

Correspondence to Joanna Atkinson.

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Atkinson, J., Edwards, R.A., Bonfanti, G. et al. A Two-Step, Trajectory-Focused, Analytics Approach to Attempt Prediction of Analgesic Response in Patients with Moderate-to-Severe Osteoarthritis. Adv Ther 40, 252–264 (2023). https://doi.org/10.1007/s12325-022-02336-6

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