Effectiveness and Tolerability of Tapentadol Prolonged Release Compared With Prior Opioid Therapy for the Management of Severe, Chronic Osteoarthritis Pain
Tapentadol prolonged release (PR; 100–250 mg twice daily) has been efficacious and well tolerated for managing moderate-to-severe, chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment.
The objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR (50–250 mg twice daily) after direct rotation from World Health Organization (WHO) step III opioids in patients with severe osteoarthritis knee pain who previously responded to WHO step III therapy but showed poor tolerability.
This open-label, phase 3b study (NCT00982280) was conducted from October 2009 through June 2010 (prematurely terminated due to slow recruitment and study drug shortages) in clinical care settings in Europe and Australia. The study population included patients with severe, chronic osteoarthritis knee pain who had taken WHO step III opioids daily for ≥2 weeks before screening, responded to therapy (average pain intensity [11-point numerical rating scale-3 (NRS-3)] ≤5 at screening), and reported opioid-related adverse effects as their reason for changing analgesics. Patients switched directly from WHO step III therapy to tapentadol. Patients received oral tapentadol PR (50–250 mg twice daily) during 5-week titration and 7-week maintenance periods. Oral tapentadol immediate release (IR) was permitted (≤twice/day, ≥4 h apart) for acute pain episodes due to index pain or withdrawal symptoms following discontinuation of previous opioids (combined dose of tapentadol [PR and IR] ≤500 mg/day). This study was planned to evaluate conversion to tapentadol PR, based on responder rate 1 (percentage of patients with same/less pain [NRS-3] versus Week −1) at Week 6 (primary endpoint), adverse events (AEs), and discontinuation rates. Equianalgesic ratios were calculated for tapentadol prior to WHO step III opioids (PR and PR plus IR formulations).
Of 82 patients enrolled, 63 received study medication. In the per-protocol population, responder rate 1 at Week 6 (last observation carried forward) was 94.3 % (50/53; P < 0.0001 vs. the null hypothesis rate [<60 %]). Mean (standard deviation) pain intensity scores were 4.7 (0.66) at baseline, 2.5 (1.46) at Week 6, and 1.8 (1.41) at Week 12 in the main analysis population (change from baseline at Weeks 6 and 12, P < 0.0001). Tapentadol to transdermal buprenorphine equianalgesic ratios (PR [n = 48], 262.9:1; PR plus IR [n = 48], 281.1:1) and tapentadol to oral oxycodone equianalgesic ratios (PR [n = 4], 4.3:1; PR plus IR [n = 6], 4.6:1) were calculated for the main analysis population. In the safety population, prevalence of AEs reported as associated with prior opioids at Week −1 (reasons for rotation) and related to tapentadol treatment at Week 12 decreased over time; the most common were nausea (46.0 vs. 24.1 %) and constipation (31.7 vs. 7.4 %). Overall, 14.3 % of patients discontinued the study early; reasons included AEs (9.5 %), lack of efficacy (3.2 %), and withdrawal of consent (1.6 %).
Significant improvements in effectiveness were observed for tapentadol PR (50–250 mg twice daily) versus WHO step III opioids in patients with severe, chronic osteoarthritis knee pain who previously responded to WHO step III therapy. Equianalgesic ratios were calculated for tapentadol to transdermal buprenorphine and oral oxycodone and were in line with observations from previous phase 3 studies.
- Altman RD, Smith HS. Opioid therapy for osteoarthritis and chronic low back pain. Postgrad Med. 2010;122(6):87–97. CrossRef
- Seed SM, Dunican KC, Lynch AM. Osteoarthritis: a review of treatment options. Geriatrics. 2009;64(10):20–9.
- Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–62. CrossRef
- Roth SH, Fleischmann RM, Burch FX, et al. Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Arch Intern Med. 2000;160(6):853–60. CrossRef
- Caldwell JR, Rapoport RJ, Davis JC, et al. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. J Pain Symptom Manage. 2002;23(4):278–91. CrossRef
- Hale M, Tudor IC, Khanna S, et al. Efficacy and tolerability of once-daily OROS hydromorphone and twice-daily extended-release oxycodone in patients with chronic, moderate to severe osteoarthritis pain: results of a 6-week, randomized, open-label, noninferiority analysis. Clin Ther. 2007;29(5):874–88. CrossRef
- Arendt-Nielsen L, Nie H, Laursen MB, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149(3):573–81. CrossRef
- Gwilym SE, Keltner JR, Warnaby CE, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009;61(9):1226–34. CrossRef
- Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–15. CrossRef
- Hochman JR, French MR, Bermingham SL, et al. The nerve of osteoarthritis pain. Arthritis Care Res (Hoboken). 2010;62(7):1019–23. CrossRef
- Nikolajsen L, Brandsborg B, Lucht U, et al. Chronic pain following total hip arthroplasty: a nationwide questionnaire study. Acta Anaesthesiol Scand. 2006;50(4):495–500. CrossRef
- Puolakka PA, Rorarius MG, Roviola M, et al. Persistent pain following knee arthroplasty. Eur J Anaesthesiol. 2010;27(5):455–60. CrossRef
- Wylde V, Hewlett S, Learmonth ID, et al. Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain. 2011;152(3):566–72. CrossRef
- Lundblad H, Kreicbergs A, Jansson KA. Prediction of persistent pain after total knee replacement for osteoarthritis. J Bone Joint Surg Br. 2008;90(2):166–71.
- Loeser RF. Molecular mechanisms of cartilage destruction in osteoarthritis. J Musculoskelet Neuronal Interact. 2008;8(4):303–6.
- Management of chronic pain syndromes: issues and interventions. Pain Med. 2005;6(Suppl 1):S1–20.
- Curatolo M, Arendt-Nielsen L, Petersen-Felix S. Central hypersensitivity in chronic pain: mechanisms and clinical implications. Phys Med Rehabil Clin N Am. 2006;17(2):287–302. CrossRef
- Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician. 2008;11(2 Suppl):S105–20.
- Furlan AD, Sandoval JA, Mailis-Gagnon A, et al. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. 2006;174(11):1589–94. CrossRef
- Porreca F, Ossipov MH. Nausea and vomiting side effects with opioid analgesics during treatment of chronic pain: mechanisms, implications, and management options. Pain Med. 2009;10(4):654–62. CrossRef
- Nuesch E, Rutjes AW, Husni E, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009;(4):CD003115.
- Tzschentke TM, Christoph T, Kögel B, et al. (-)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel μ-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther. 2007;323(1):265–76. CrossRef
- Tzschentke TM, De Vry J, Terlinden R, et al. Tapentadol HCl. Drugs Future. 2006;31(12):1053–61. CrossRef
- Afilalo M, Etropolski MS, Kuperwasser B, et al. Efficacy and safety of tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study. Clin Drug Investig. 2010;30(8):489–505. CrossRef
- Lange B, Kuperwasser B, Okamoto A, et al. Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain. Adv Ther. 2010;27(6):381–99. CrossRef
- Wild JE, Grond S, Kuperwasser B, et al. Long-term safety and tolerability of tapentadol extended release for the management of chronic low back pain or osteoarthritis pain. Pain Pract. 2010;10(5):416–27. CrossRef
- Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled phase III study. Expert Opin Pharmacother. 2010;11(11):1787–804. CrossRef
- Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27(1):151–62. CrossRef
- Vinik A, Shapiro DY, Rauschkolb C, et al. Efficacy and tolerability of tapentadol extended release (ER) in patients with chronic, painful diabetic peripheral neuropathy (DPN): results of a phase 3, randomized-withdrawal, placebo-controlled study [abstract]. J Pain. 2012;13(Suppl 4):S72.
- Steigerwald I, Müller M, Kujawa J, et al. Effectiveness and safety of tapentadol prolonged release with tapentadol immediate release on-demand for the management of severe, chronic osteoarthritis-related knee pain: results of an open-label, phase 3b study. J Pain Res. 2012;5:121–38. CrossRef
- Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1–2):9–19. CrossRef
- Farrar JT, Young JP Jr, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149–58. CrossRef
- Schneider LS, Olin JT, Doody RS, et al. Validity and reliability of the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(Suppl 2):S22–32. CrossRef
- Bellamy N. WOMAC Osteoarthritis Index: user guide IV. Brisbane: WOMAC; 2000.
- Selai CE, Trimble MR, Price MJ, et al. Evaluation of health status in epilepsy using the EQ-5D questionnaire: a prospective, observational, 6-month study of adjunctive therapy with anti-epileptic drugs. Curr Med Res Opin. 2005;21(5):733–9. CrossRef
- Ware JE Jr, Donald Sherbourne C. The MOS 36-item Short-Form Health Survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83. CrossRef
- Bjelland I, Dahl AA, Haug TT, et al. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002;52(2):69–77. CrossRef
- Haythornthwaite JA, Hegel MT, Kerns RD. Development of a sleep diary for chronic pain patients. J Pain Symptom Manage. 1991;6(2):65–72. CrossRef
- Snaith RP. The Hospital Anxiety And Depression Scale. Health Qual Life Outcomes. 2003;1:29. CrossRef
- Combe R, Bramwell S, Field MJ. The monosodium iodoacetate model of osteoarthritis: a model of chronic nociceptive pain in rats? Neurosci Lett. 2004;370(2–3):236–40. CrossRef
- Ho KY, Tay W, Yeo MC, et al. Duloxetine reduces morphine requirements after knee replacement surgery. Br J Anaesth. 2010;105(3):371–6. CrossRef
- Schaible HG. Peripheral and central mechanisms of pain generation. Handb Exp Pharmacol. 2007;177:3–28. CrossRef
- Agency for Healthcare Research and Quality. http://www.ahrq.gov. Accessed 2 Oct 2006.
- Effectiveness and Tolerability of Tapentadol Prolonged Release Compared With Prior Opioid Therapy for the Management of Severe, Chronic Osteoarthritis Pain
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- 1. Medical Affairs Europe and Australia, Grünenthal GmbH, Zieglerstrasse 6, 52078, Aachen, Germany
- 2. Community Havelhöhe, Center for Pain and Palliative Care, Berlin, Germany
- 3. Medical Treatment and Research Center, Zerbst, Germany
- 4. Department of Orthopedic Surgery, Hvidovre University Hospital, Copenhagen, Denmark
- 5. Pain Management Clinic, Solihull Hospital, Solihull, UK