Hydromorphone extended release for neuropathic and non-neuropathic/nociceptive chronic low back pain: A post hoc analysis of data from a randomized, multicenter, double-blind, placebo-controlled clinical trial

Srinivas Nalamachu, MD; Martin Hale, MD; Arif Khan, MD

doi:10.5055/jom.2014.0221

Authors

Srinivas Nalamachu, MD
Martin Hale, MD
Arif Khan, MD

DOI:

https://doi.org/10.5055/jom.2014.0221

Keywords:

hydromorphone, neuropathic pain, low back pain, opioids

Abstract

Objective: The aim of this study was to determine the efficacy and tolerability of hydromorphone extended release (ER) in patients with chronic low back pain (LBP) with or without a neuropathic component.

Design: This was a post hoc analysis of data from a multicenter, double-blind, placebo-controlled clinical trial using a randomized withdrawal design, performed in patients with moderate to severe chronic LBP. Patients achieving stable doses of hydromorphone ER during a 2- to 4-week conversion and titration phase were randomized to continue treatment with hydromorphone ER or taper-down to placebo during a 12-week double-blind phase. The primary efficacy outcome was the mean change in 11-point Numeric Rating Scale (NRS) pain intensity score from randomization to the final visit of the double-blind phase. Tolerability was assessed by recording adverse events (AEs). Data were analyzed separately for patients with non-neuropathic and neuropathic LBP.

Results: A total of 173 patients with non-neuropathic/nociceptive LBP and 94 with neuropathic LBP were randomized into the double-blind phase. During the conversion and titration phase, mean (SD) NRS scores decreased significantly from 6.5 (1.87) and 6.4 (1.99) at screening to 3.3 (0.98) and 3.2 (1.05), respectively. For both LBP subgroups, patients randomized to hydromorphone ER maintained this improvement over the double-blind treatment period, whereas those randomized to placebo reported significant increase in NRS scores. Across subgroups, the incidence of 1 or more AE was 54 percent to 57 percent in the conversion and titration phase and 47 percent to 55 percent in the double-blind phase.

Conclusions: The results of this study indicate that hydromorphone ER is efficacious and generally well tolerated in the management of patients with non-neuropathic and neuropathic chronic LBP.

Author Biographies

Srinivas Nalamachu, MD

International Clinical Research Institute, Overland Park, Kansas

Martin Hale, MD

Gold Coast Research, LLC, Weston, Florida

Arif Khan, MD

Northwest Clinical Research Center, Bellevue, Washington; Duke University Medical Center, Durham, North Carolina

References

Woolf AD, Pfleger B: Burden of major musculoskeletal conditions. Bull World Health Organ. 2003; 81(9): 646-656.

Gore M, Sadosky A, Stacey BR, et al.: The burden of chronic low back pain: Clinical comorbidities, treatment |patterns, and health care costs in usual care settings. Spine (Phila Pa 1976). 2012; 37(11): E668-E677.

Attal N, Perrot S, Fermanian J, et al.: The neuropathic components of chronic low back pain: A prospective multicenter study using the DN4 Questionnaire. J Pain. 2011; 12(10): 1080-1087.

Yarnitsky D, Eisenberg E: Neuropathic pain: Between the positive and negative ends. Pain Forum. 1998; 7(4): 241-242.

Eisenberg E, McNicol ED, Carr DB: Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: Systematic review and meta-analysis of randomized controlled trials. JAMA. 2005; 293(24): 3043-3052.

von Hehn CA, Baron R, Woolf CJ: Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012; 73(4): 638-652.

Dworkin RH, O'Connor AB, Audette J, et al.: Recommendations for the pharmacological management of neuropathic pain: An overview and literature update. Mayo Clin Proc. 2010; 85(Suppl 3): S3-14.

Sindrup SH, Jensen TS: Efficacy of pharmacological treatments of neuropathic pain: An update and effect related to mechanism of drug action. Pain. 1999; 83(3): 389-400.

Eisenberg E, McNicol E, Carr DB: Opioids for neuropathic pain. Cochrane Database Syst Rev. 2006; (3): CD006146.

Huse E, Larbig W, Flor H, et al.: The effect of opioids on phantom limb pain and cortical reorganization. Pain. 2001; 90(1-2): 47-55.

Raja SN, Haythornthwaite JA, Pappagallo M, et al.: Opioids versus antidepressants in postherpetic neuralgia: A randomized, placebo-controlled trial. Neurology. 2002; 59(7): 1015-1021.

Watson CP, Moulin D, Watt-Watson J, et al.: Controlledrelease oxycodone relieves neuropathic pain: A randomized controlled trial in painful diabetic neuropathy. Pain. 2003; 105(1-2): 71-78.

Bartleson JD: Evidence for and against the use of opioid analgesics for chronic nonmalignant low back pain: A review. Pain Med. 2002; 3(3): 260-271.

Mallinckrodt Brand Pharmaceuticals: Exalgo (hydromorphone HCl) extended-release tablets [package insert]. Hazelwood, MO: Mallinckrodt Brand Pharmaceuticals, Inc., 2012.

Hale M, Khan A, Kutch M, et al.: Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain. Curr Med Res Opin. 2010; 26(6): 1505-1518.

Quebec Task Force on Spinal Disorders: Scientific approach to the assessment and management of activity-related spinal disorders. A monograph for clinicians. Report of the Quebec Task Force on Spinal Disorders. Spine (Phila Pa 1976 ). 1987; 12(7 Suppl): S1-S59.

Hjermstad MJ, Fayers PM, Haugen DF, et al.: Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: A systematic literature review. J Pain Symptom Manage. 2011; 41(6): 1073-1093.

Roland M, Fairbank J: The Roland-Morris Disability Questionnaire and the Oswestry Disability Questionnaire. Spine (Phila Pa 1976). 2000; 25(24): 3115-3124.

Rothman M, Vallow S, Damaraju CV, et al.: Using the patient global assessment of the method of pain control to assess new analgesic modalities in clinical trials. Curr Med Res Opin. 2009; 25(6): 1433-1443.

Butler SF, Black RA, Cassidy TA, et al.: Abuse risks and routes of administration of different prescription opioid compounds and formulations. Harm Reduct J. 2011; 8: 29.

Fine PG, Mahajan G, McPherson ML: Long-acting opioids and short-acting opioids: Appropriate use in chronic pain management. Pain Med. 2009; 10(Suppl 2): S79-S88.

Gupta S, Sathyan G: Providing constant analgesia with OROS® hydromorphone. J Pain Symptom Manage. 2007; 33(2S): S19-S24.

Shram MJ, Sathyan G, Khanna S, et al.: Evaluation of the abuse potential of extended release hydromorphone versus immediate release hydromorphone. J Clin Psychopharmacol. 2010; 30(1): 25-33.

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): 874-888.

Wallace M, Skowronski R, Khanna S, et al.: Efficacy and safety evaluation of once-daily OROS hydromorphone in patients with chronic low back pain: A pilot open-label study (DO-127). Curr Med Res Opin. 2007; 23(5): 981-989.

Hanna M, Thipphawong J, 118 Study Group: A randomized, double-blind comparison of OROS® hydromorphone and controlled- release morphine for the control of chronic cancer pain. BMC Palliat Care. 2008; 7: 17-31.

Binsfeld H, Szczepanski L, Waechter S, et al.: A randomized study to demonstrate noninferiority of once-daily OROS® hydromorphone with twice-daily sustained-release oxycodone for moderate to severe chronic noncancer pain. Pain Pract. 2010; 10(5): 404-415.

Carter NJ, Keating GM: OROS hydromorphone prolonged release: A review of its use in the management of chronic, moderate to severe pain. CNS Drugs. 2010; 24(4): 337-361.

Moulin DE, Richarz U, Wallace M, et al.: Efficacy of the sustained-release hydromorphone in neuropathic pain management: Pooled analysis of three open-label studies. J Pain Palliat Care Pharmacother. 2010; 24(3): 200-212.

Wallace M, Thipphawong J: Open-label study on the longterm efficacy, safety, and impact on quality of life of OROS hydromorphone ER in patients with chronic low back pain. Pain Med. 2010; 11(10): 1477-1488.

Nalamachu SR, Kutch M, Hale ME: Safety and tolerability of once-daily OROS® hydromorphone extended-release in opioid- tolerant adults with moderate-to-severe chronic cancer and noncancer pain: Pooled analysis of 11 clinical studies. J Pain Symptom Manage. 2012; 44(6): 852-865.

Haanpaa M, Attal N, Backonja M, et al.: NeuPSIG guidelines on neuropathic pain assessment. Pain. 2011; 152(1): 14-27.