Date of Award
1-1-2025
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
John P. Bentley
Second Advisor
Yinan Huang
Third Advisor
Yi Yang
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Objectives: Pain is the most common patient-reported outcome in rheumatoid arthritis (RA), frequently managed with long-term opioid therapy (LTOT), despite limited evidence supporting its efficacy and safety. Given the inflammatory nature of RA pain, biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may relief pain and facilitate opioid withdrawal. This study compared rates of any opioid tapering, rapid opioid tapering, and opioid discontinuation among Medicare beneficiaries with RA who initiated b/tsDMARDs, including tumor necrosis factor inhibitors (TNFi bDMARDs), non-TNFi bDMARDs, or Janus kinase inhibitors (JAKi).
Methods: A new-user cohort study design was implemented using 5% Medicare (2012-2020). Beneficiaries with RA, who initiated b/tsDMARDs (first prescription=index date) and had ≥45 days of opioid possession in the 90 days preceding the index date, were identified and followed until outcome/censoring. Inverse probability of treatment weighting (IPTW) using generalized propensity scores estimated via generalized boosted models (GBM) was employed to adjust for baseline differences. Separate Cox proportional hazards models incorporating the GBM-derived IPTWs were applied to evaluate the risk of study outcomes across b/tsDMARDs. Alternative LTOT definitions were tested to assess sensitivity.
Results: The cohort included 1,428 individuals (mean [SD] age: 63.87 [12.30]; 77.73% female), with 60.64% initiating TNFi bDMARDs, 33.54% non-TNFi bDMARDs, and 5.81% JAKi. Compared to JAKi initiators, TNFi bDMARDs initiators had a lower hazard of opioid tapering (aHR [95% CI] = 0.70 [0.56–0.88]), as did non-TNFi bDMARDs initiators, though with less precision (aHR [95% CI] = 0.82 [0.65–1.02]). Non-TNFi bDMARDs initiators had a higher hazard of opioid discontinuation compared to JAKi (aHR [95% CI] = 1.64 [1.10–2.45]). Similarly, TNFi bDMARDs initiators had a higher hazard of opioid discontinuation, though with less precision (aHR [95% CI] = 1.42 [0.98–2.07]). Rapid opioid tapering rates were comparable across groups. Tapering results were consistent across LTOT definitions, while discontinuation findings were sensitive to definition changes.
Conclusion: Among Medicare beneficiaries with RA on LTOT, bDMARDs initiation was associated with lower tapering but higher discontinuation rates compared to JAKi initiation, though opioid discontinuation results were sensitive to LTOT definition. These findings underscore the need to optimize b/tsDMARDs selection for better pain management.
Recommended Citation
Bazzazzadehgan, Shadi, "Comparative Effectiveness of Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Terms of Opioid Tapering and Discontinuation among Medicare Beneficiaries with Rheumatoid Arthritis" (2025). Electronic Theses and Dissertations. 3243.
https://egrove.olemiss.edu/etd/3243