Cover: Time-varying Treatment Effect Modification of Oral Analgesic Effectiveness by Depressive Symptoms in Knee Osteoarthritis

Time-varying Treatment Effect Modification of Oral Analgesic Effectiveness by Depressive Symptoms in Knee Osteoarthritis

An Application of Structural Nested Mean Models in a Prospective Cohort

Published in: International Journal of Epidemiology, Volume 53, Issue 1 (February 2024). DOI: 10.1093/ije/dyad152

Posted on rand.org Apr 17, 2024

by Alan M. Rathbun, Michelle D. Shardell, Joseph J. Gallo, Alice S. Ryan, Elizabeth A. Stuart, Megan S. Schuler, Yu Dong, Brock A. Beamer, Rhea Mehta, Jason E. Peer, et al.

Background

Depressive symptoms are common in knee osteoarthritis (OA), exacerbate knee pain severity and may influence outcomes of oral analgesic treatments. The aim was to assess whether oral analgesic effectiveness in knee OA varies by fluctuations in depressive symptoms.

Methods

The sample included Osteoarthritis Initiative (OAI) participants not treated with oral analgesics at enrollment (n=1477), with radiographic disease at the first follow-up visit (defined as the index date). Oral analgesic treatment and depressive symptoms, assessed with the Center for Epidemiological Studies Depression [(CES-D) score ≥16] Scale, were measured over three annual visits. Knee pain severity was measured at visits adjacent to treatment and modifier using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (rescaled range = 0-100). Structural nested mean models (SNMMs) estimated causal mean differences in knee pain severity comparing treatment versus no treatment.

Results

The average causal effects of treated versus not treated for observations without depressive symptoms showed negligible differences in knee pain severity. However, causal mean differences in knee pain severity comparing treatment versus no treatment among observations with depressive symptoms increased over time from -0.10 [95% confidence interval (CI): -9.94, 9.74] to -16.67 (95% CI: -26.33, -7.01). Accordingly, the difference in average causal effects regarding oral analgesic treatment for knee pain severity between person-time with and without depressive symptoms was largest (-16.53; 95% CI: -26.75, -6.31) at the last time point. Cumulative treatment for 2 or 3 years did not yield larger causal mean differences.

Conclusions

Knee OA patients with persistent depressive symptoms and chronic pain may derive more analgesic treatment benefit than those without depressive symptoms and less pain.

Research conducted by

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