Comparative risk-benefit profiles of weak opioids in the treatment of osteoarthritis: a network meta-analysis of randomized controlled trials

ABSTRACT

Background

Despite their poor tolerance, weak opioids are still the most commonly-prescribed medicine for osteoarthritis (OA)-related pain. The objective of this network meta-analysis was to comparatively examine the efficacy and safety of weak opioids in OA treatment.

Methods

Databases including PubMed, Embase, Cochrane Library and Web of Science were searched from inception to 4 April 2022 to retrieve randomized controlled trials (RCTs) comparing weak opioids with placebo or between one another in OA patients. Bayesian network meta-analysis was performed on the following outcomes of interest, namely the change-from-baseline score in pain relief, gastrointestinal (GI) adverse events (AEs), central nervous system (CNS) AEs, and total number of AEs (i.e. the number of subjects experiencing any AE for at least once) during follow-up. The surface under the cumulative ranking curve (SUCRA) was used to rank the effectiveness of each treatment and identify the best treatment.

Results

A total of 14 RCTs invoving four types of weak opioids were included in this meta-analysis. Compared to placebo, tramadol (standardized mean difference [SMD] = −0.34, 95% credible interval [CrI]: −0.53 to −0.18) and codeine (SMD = −0.39, 95% CrI: −0.79 to −0.04) were effective for pain relief, but involved a higher risk of GI AEs, CNS AEs and total number of AEs. Dextropropoxyphene demonstrated a significantly lower risk of GI AEs (OR = 0.28, 95%CrI: 0.17 to 0.51), CNS AEs (OR = 0.29, 95%CrI: 0.11 to 0.78) and total number of AEs (OR = 0.35, 95%CrI: 0.15 to 0.82) compared to codeine. Dihydrocodeine had a better safety profile in CNS AEs (SUCRA = 64.8%) and total number of AEs (SUCRA = 66.6%).

Conclusions

The results of the present study confirmed that tramadol and codeine were effective drugs for the treatment of OA, but involved considerable safety issues. Dextropropoxyphene and dihydrocodeine exhibited a relatively good safety profile but their efficacy still warrant further investigation.

KEYWORDS:

• Weak opioids
• osteoarthritis
• network meta-analysis

Abbreviations

OA: osteoarthritis; RCTs: randomized controlled trials; GI: gastrointestinal; AEs: adverse events; CNS: central nervous system; SMD: standardized mean difference; CrI: credible interval; NMA: network meta-analysis; ORs: odds ratios; SUCRA, surface under the cumulative ranking curve; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; NSAIDs: non-steroidal anti-inflammatory drugs.

Acknowledgments

Everyone who contributed significantly to the work has been listed.

Disclosures of any financial/other conflicts of interest

The authors have no relevant conflicts of interest to disclose. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethics approval and consent to participate

Ethics approval was not required as this is a network meta-analysis. Not applicable.

Consent for publication

This study contains no personal patient data. Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author contributions

W.L. and H.H. had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors have read, provided critical feedback on intellectual content and approved the final manuscript. Concept and design: D.X. and W.L. Acquisition and interpretation of data: W.L., Z.Y. and H.H. Statistical analysis: W.L. and Z.Y. Drafting of the manuscript: W.L. Critical revision of the manuscript for important intellectual content: Z.W. and D.X. Study supervision: Z.W. and D.X.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/00325481.2022.2080360

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81772413, 81930071, 81902265, 82072502), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, 2020LNJJ03), and the Science and Technology Program of Hunan Province (2019RS2010). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.