Sublingual, transdermal and intravenous patient-controlled analgesia for acute post-operative pain: systematic literature review and mixed treatment comparison

Abstract

Objective: To conduct a systematic literature review (SLR) and quantitative analysis to assess the comparative efficacy and safety of the sufentanil sublingual tablet system (SSTS) against other available patient controlled analgesia (PCA) options for post-operative analgesia.

Methods: An SLR was conducted for studies published between 2004 and 2016. Due to study heterogeneity, subgroup analyses were conducted controlling for differences in imputation methods for missing values, baseline pain severity, and type of surgery. Where sufficient data was available, a mixed treatment comparison (MTC) was performed.

Results: The MTC and subgroup analyses used 13 studies. In direct meta-analysis, there was a statistically significant difference in favor of SSTS compared with intravenous (IV) PCA (morphine) at 24 hours for the patient global assessment (PGA) scores of “good” or “excellent”. For the Pain Intensity Score, there were numerical but not statistically significant differences in favor of the SSTS versus IV PCA (morphine) and the patient controlled transdermal system (PCTS) (fentanyl) in the MTC at 6 hours (standardized mean difference −0.27 [credible interval −2.78, 2.09] and −0.36 [−3.89, 3.03], respectively). The onset of pain relief was earlier with the SSTS versus IV PCA (morphine) as shown by the Pain Intensity Difference. Likewise, the onset was earlier compared with PCTS (fentanyl) where data was available. There was a significant difference in favor of SSTS compared with IV PCA (morphine) and with PCTS (fentanyl) for any adverse event, and numerical improvements for withdrawals due to adverse events.

Conclusions: This meta-analysis shows that SSTS is an option for non-invasive management of moderate-to-severe post-operative pain which can be more effective, faster in onset and better tolerated than IV PCA (morphine) and PCTS (fentanyl).

Keywords:

• Administration
• analgesia
• analgesics
• cutaneous
• meta-analysis
• opioid
• pain
• patient-controlled
• post-operative
• sufentanil
• systematic literature review

Transparency

Declaration of funding

This work was conducted by Parexel International and funded by Grünenthal GmbH.

Author contributions: S.T., H.L. and P.K. were involved in the design, analysis and interpretation of the data, and review and final approval of the manuscript. P.P. was involved in the analysis, interpretation, review and final approval of the manuscript.

Declaration of financial/other relationships

H.L. and P.K. have disclosed that they are employees of Grünenthal GmbH who market Zalviso in the EU. P.P. has disclosed that she is an employee of AcelRx Pharmaceuticals who will market Zalviso in the US. S.T. has disclosed that she is an employee of Parexel International.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

The authors acknowledge the assistance of Barinder Singh and Sumeet Attri with data extraction and conduct of the SLR and of Sue Neville with drafting the manuscript (all working for Parexel Market Access). The systematic literature review did not undergo formal registration; however, the review was conducted using a robust and unbiased methodology.

Notes

1 Zalviso (R) is a registered trade name of Grünenthal GmbH, Aachen, Germany for Europe and AcelRx Pharmaceuticals, INC., Redwood City, USA

2 Ionsys (R) is a registered trade name of Incline Therapeutics Europe Ltd, 21 St. Thomas Street Bristol BS1 6JS, UK