Effectiveness and safety of tapentadol prolonged release for severe, chronic low back pain with or without a neuropathic pain component: results of an open-label, phase 3b study

Abstract

Objective:

This open-label, phase 3b study evaluated the effectiveness and tolerability of tapentadol prolonged release and tapentadol immediate release (for acute pain episodes) for severe, chronic low back pain with or without a neuropathic pain component that was inadequately managed in patients taking World Health Organization (WHO) Step I or II analgesics or who were not regularly treated with analgesics.

Research design and methods:

Average baseline pain intensity was greater than 5 (11-point numerical rating scale-3 [NRS-3; 3-day average pain intensity]) with WHO Step I or II analgesics and greater than 6 with no regular analgesic regimen. WHO Step II analgesics were discontinued before starting study treatment; WHO Step I analgesics or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50–250 mg bid) during a 5-week titration and 7-week maintenance period. Tapentadol immediate release was permitted for acute pain episodes (tapentadol prolonged release and immediate release maximum combined dose, ≤500 mg/day). The painDETECT questionnaire was used to define subsets of patients based on the probability of a neuropathic pain component to their low back pain as ‘negative’, ‘unclear’, or ‘positive’.

Clinical trial registration: NCT00983385.

Main outcome measure:

The primary endpoint was the change from baseline to week 6 in average pain intensity (NRS-3), using the last observation carried forward to impute missing scores.

Results:

In the painDETECT negative (n = 49) and unclear/positive (n = 126) subsets, respectively, mean (SD) changes in pain intensity from baseline to week 6 were −2.4 (2.18) and −3.0 (2.07; both p < 0.0001). Among patients who had not received prior WHO Step II treatment, lower doses of tapentadol prolonged release were generally required with increasing likelihood of a neuropathic pain component. Based on the painDETECT questionnaire and the Neuropathic Pain Symptom Inventory (NPSI), tapentadol prolonged release treatment was also associated with significant improvements in neuropathic pain symptoms, with decreases in the number of pain attacks and the duration of spontaneous pain in the last 24 hours in patients with low back pain with a neuropathic pain component (painDETECT unclear or positive score at baseline or screening). The most common treatment-emergent adverse events (incidence ≥10%, n = 176) were nausea, dizziness, headache, dry mouth, fatigue, constipation, diarrhea, nasopharyngitis, and somnolence.

Conclusions:

Tapentadol prolonged release was well tolerated and effective for managing severe, chronic low back pain with or without a neuropathic pain component.

Key words::

• Chronic pain
• Low back pain
• Neuropathic pain
• Tapentadol prolonged release

Transparency

Declaration of funding

This study was sponsored by Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany.

Declaration of financial/other relationships

I.S. and M.M. are employees of Grünenthal GmbH, Aachen, Germany. A.D. has received honoraria from Grünenthal for advisory board meetings, has received honoraria from Grünenthal and Pfizer for faculty educational meetings, and has received an unrestricted educational grant from Grünenthal to attend the annual scientific meeting of the European Federation of International Association for the Study of Pain (IASP) Chapters (EFIC). D.S. served as a member of an advisory board for tapentadol for Grünenthal. R.S. has received funds as a principal investigator from Grünenthal GmbH, Allergan, and Astella and has received speaker’s honoraria from MSD and Janssen-Cilag GmbH. R.B. has received grants or research funding from Pfizer, Genzyme, Grünenthal, the German Federal Ministry of Education and Research (BMBF), the German Research Network on Neuropathic Pain, Modelling Pain Switches, and the German Research Foundation (DFG); has served as a member of the IMI ‘Europain’ collaboration (which includes the following industry members: AstraZeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly, Neuroscience Technologies, and Boehringer Ingelheim); and has participated in speakers bureaus for Pfizer, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, UCB BioSciences, Lilly, Boehringer Ingelheim, Astellas, Novartis, and Bristol-Myers Squibb. S.R. has received honoraria as an investigator from Grünenthal GmbH and has served as a member of a board on gouty arthritis for the Menarini Group. H.G.K. has received sponsorship from Grünenthal; has served as a consultant/advisor for Grünenthal and Mundipharma, and has participated in speakers bureaus for Grünenthal, Eisai, and Cephalon. A.G. and A.S-S. have no conflicts of interest to disclose.

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.

Acknowledgments

Editorial support for the writing of this manuscript was provided by Megan Knagge, PhD, of MedErgy, and was funded by Medical Affairs Europe & Australia, Grünenthal GmbH, Aachen, Germany. The authors retained full editorial control over the content of the manuscript.

Previous presentations: Results of this study were presented, in part, at the New York School of Regional Anesthesia World Anesthesia Congress (NWAC), April 11–15, 2011, Rome, Italy; the 44th Annual Scientific Meeting of the British Pain Society, June 21–24, 2011, Edinburgh, UK; the 34th National Congress of the Italian Association for the Study of Pain (AISD), May 29–31, 2011, Riccione, Italy; and the 7th Congress of the European Federation of IASP Chapters (EFIC), September 21–24, 2011, Hamburg, Germany.