Systematic review of tapentadol in chronic severe pain

Abstract

Aim:

A systematic review of chronic pain treatment with strong opioids (step 3 WHO pain ladder) and a comparison to a new drug recently approved for the treatment of severe chronic pain in Europe, tapentadol (Palexia, Nucynta

*Co-manufactured. Palexia is a registered trade name of Grünenthal, Aachen Germany. Nucynta is a registered trade name of Johnson and Johnson, New Brunswick, NJ, USA.

), were performed.

Methods:

Thirteen electronic databases were searched as well as a number of other sources from 1980 up to November 2010 for relevant randomized controlled clinical trials in chronic moderate and severe pain investigating at least one step 3 opioid. Chronic pain could be nociceptive or neuropathic, malignant or non-malignant, all systemic administrations were considered as well as trials of different lengths. Two separate analyses were performed, one only for trials which reported (at least as sub-groups) the outcome in patients with severe pain, the other including both moderate and severe pain conditions. With the exception of the direct comparison between tapentadol, oxycodone and placebo, indirect comparisons were performed based on a network analysis. Trials with an enriched or an enriched withdrawal design were excluded. Primary (pain intensity) and a number of secondary endpoints were evaluated, including pain relief (30% and 50%), patient global impression of change, quality of life, quality of sleep, discontinuations, as well as serious adverse events and selected adverse events.

Results:

Only 10 trials were eligible for analysis of patients with severe pain (eight investigating tapentadol and two trials comparing buprenorphine patch vs placebo). For moderate and severe pain, 42 relevant trials were identified and indirect comparisons with transdermal buprenorphine, transdermal fentanyl, hydromorphone, morphine, and oxymorphone were performed. This report focuses on the network analysis. Tapentadol showed statistically favourable results over oxycodone for pain intensity, 30% and 50% pain relief, patient global impression of change (PGIC), and quality of life. Furthermore, some of the most important adverse events of chronic opioid treatment were significantly less frequent with tapentadol as compared to oxycodone, i.e. constipation, nausea, and vomiting; discontinuations due to these adverse events were found significantly reduced with tapentadol. Similar results were obtained for the network analysis, i.e. tapentadol was superior for the primary outcome (pain intensity) to hydromorphone and morphine, whereas fentanyl and oxymorphone showed trends in favour of these treatments. Significantly less frequent gastrointestinal adverse events of tapentadol were observed in comparison with fentanyl, hydromorphone, morphine, and oxymorphone, apparently leading to significantly reduced treatment discontinuations (for any reason).

Conclusions:

Taken together, the benefit–risk ratio of tapentadol appears to be improved compared to step 3 opioids.

Key words::

• Chronic pain
• Opioids
• Systematic review
• Tapentadol

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Erratum

Transparency

Declaration of funding

The project was funded by Grünenthal Gmbh, Germany. R.R. and J.K. had ultimate editorial control of the manuscript.

Declaration of financial/other relationships

S.St. was a former employee of Grünenthal (until January 2010) but has contributed to this manuscript as a consultant (including consultancy services to Grünenthal). M.S. has disclosed that he has served as a consultant to Grünenthal GmbH. R.R., C.F., J.H., G.W., K.M. and J.K. have disclosed that they are employees of Kleijnen Systematic Reviews Ltd, a company that received funding from Grünenthal to conduct this study.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

All contributions were made by authors only.

Contributions of authors: R.R. (Senior Research Fellow), C.F. (Reviews Manager) and J.H. (Systematic Reviewer) assessed abstracts and titles for inclusion and exclusion, conducted the original systematic review, and contributed to writing and editing this manuscript. G.W. (Statistician) contributed to the meta-analyses and K.M. (Information Specialist) planned the search strategy and ran the searches. S.St. (Clinical Expert) advised on clinical matters and the interpretation of the data and contributed to the writing of the manuscript. M.S. (Medical Advisor) advised on clinical matters and the interpretation of the data and contributed to the writing of the manuscript. J.K. (Director) provided overall project management, wrote the protocol, assessed abstracts and titles for inclusion and exclusion, conducted the systematic review, and contributed to writing and editing the manuscript. All authors read and approved the final manuscript.

Notes

*Co-manufactured. Palexia is a registered trade name of Grünenthal, Aachen Germany. Nucynta is a registered trade name of Johnson and Johnson, New Brunswick, NJ, USA.

*Co-manufactured. Palexia is a registered trade name of Grünenthal, Aachen Germany. Nucynta is a registered trade name of Johnson and Johnson, New Brunswick, NJ, USA.