Pain intensity and interference with functioning and well-being in subgroups of patients with chronic pain treated with once-daily hydrocodone tablets

Adrian Bartoli, MD; Edward Michna, MD; Ellie He, PhD; Warren Wen, PhD

doi:10.5055/jom.2015.0305

Authors

Adrian Bartoli, MD
Edward Michna, MD
Ellie He, PhD
Warren Wen, PhD

DOI:

https://doi.org/10.5055/jom.2015.0305

Keywords:

hydrocodone, opioids, long-term

Abstract

Background: A previous 52-week trial of patients with chronic noncancer, nonneuropathic pain (CNNP) showed clinically meaningful improvement in pain intensity, pain interference, and physical health-related quality of life (HRQL) following daily treatment with an extended-release, once-daily hydrocodone (Hysingla® ER; HYD) bitartrate tablet.

Objective: To examine treatment response within patient subgroups and to assess between-subgroup differences in effectiveness and side effect profile.

Methods: Data were from an open-label 52-week trial of treatment with HYD tablets (20-120 mg, once-daily) for patients with moderate-to-severe CNNP. Binary subgroups were defined for the following six factors: age, gender, opioid experience, baseline pain severity, history of depression, and stable HYD dose at completion of a 45-day dose-titration period. Univariable and multivariable models examined changes in average pain intensity (API; 11-point numeric rating scale), pain interference (Brief Pain Inventory-Interference subscale [BPI-I]), physical and mental HRQL (36-item Short Form health survey Physical and Mental Component Summaries [PCS and MCS]), and sleep quality (Medical Outcomes Study Sleep Scale Sleep Problems Index [SPI]) from baseline to maintenance, and subgroup differences in adverse events.

Results: All subgroups showed clinically meaningful improvements in API, BPII, and PCS scores; no subgroups showed improvements in MCS or SPI. Between subgroup comparisons found greater improvements for opioid-naïve patients and for patients with severe baseline pain. Incidence of adverse events differed minimally between subgroups.

Conclusion: Regardless of subgroup, patients with CNNP treated with HYD showed clinically meaningful improvements in pain intensity, pain interference, and physical HRQL, although not in mental HRQL or sleep quality. Improvements were generally larger for opioid-naïve patients and patients with severe baseline pain.

Author Biographies

Adrian Bartoli, MD

San Francisco Pain Management Center, San Francisco, California

Edward Michna, MD

Brigham and Women’s Hospital, Boston, Massachusetts.

Ellie He, PhD

Purdue Pharma L.P., Stamford, Connecticut

Warren Wen, PhD

Purdue Pharma L.P., Stamford, Connecticut

References

Fishbain DA, Cole B, Lewis JE, et al.: What is the evidence for chronic pain being etiologically associated with the DSM-IV category of sleep disorder due to a general medical condition? A structured evidence-based review. Pain Med. 2010; 11(2): 158-179.

Hoffman DL, Dukes EM: The health status burden of people with fibromyalgia: A review of studies that assessed health status with the SF-36 or the SF-12. Int J Clin Pract. 2008; 62(1): 115-126.

Kelly GA, Blake C, Power CK, et al.: The association between chronic low back pain and sleep: A systematic review. Clin J Pain. 2011; 27(2): 169-181.

Kiebzak GM, Campbell M, Mauerhan DR: The SF-36 General Health Status Survey documents the burden of osteoarthritis and the benefits of total joint arthroplasty: But why should we use it? Am J Manag Care. 2002; 8(5): 463-474.

Menefee LA, Frank ED, Doghramji K, et al.: Self-reported sleep quality and quality of life for individuals with chronic pain conditions. Clin J Pain. 2000; 16(4): 290-297.

Ovayolu N, Ovayolu O, Karadag G: Health-related quality of life in ankylosing spondylitis, fibromyalgia syndrome, and rheumatoid arthritis: A comparison with a selected sample of healthy individuals. Clin Rheumatol. 2011; 30(5): 655-664.

Salaffi F, de Angelis R, Stancati A, et al.: Health-related quality of life in multiple musculoskeletal conditions: A cross-sectional population based epidemiological study. II. The MAPPING study. Clin Exp Rheumatol. 2005; 23(6): 829-839.

Salaffi F, Carotti M, Gasparini S, et al.: The health-related quality of life in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: A comparison with a selected sample of healthy people. Health Qual Life Outcomes. 2009; 7: 25.

Schaefer C, Chandran A, Hufstader M, et al.: The comparative burden of mild, moderate and severe fibromyalgia: Results from a cross-sectional survey in the United States. Health Qual Life Outcomes. 2011; 9: 71.

Uhlig T, Loge JH, Kristiansen IS, et al.: Quantification of reduced health-related quality of life in patients with rheumatoid arthritis compared to the general population. J Rheumatol. 2007; 34(6): 1241-1247.

Wolfe F, Michaud K, Li T: Sleep disturbance in patients with rheumatoid arthritis: Evaluation by medical outcomes study and visual analog sleep scales. J Rheumatol. 2006; 33(10): 1942-1951.

Arnold LM, Chatamra K, Hirsch I, et al.: Safety and efficacy of esreboxetine in patients with fibromyalgia: An 8-week, multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2010; 32(9): 1618-1632.

Bennett RM, Schein J, Kosinski MR, et al.: Impact of fibromyalgia pain on health-related quality of life before and after treatment with tramadol/acetaminophen. Arthritis Rheum. 2005; 53(4): 519-527.

Boonen A, Patel V, Traina S, et al.: Rapid and sustained improvement in health-related quality of life and utility for 72 weeks in patients with ankylosing spondylitis receiving etanercept. J Rheumatol. 2008; 35(4): 662-667.

Crofford LJ, Mease PJ, Simpson SL, et al.: Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): A 6-month, double-blind, placebo-controlled trial with pregabalin. Pain. 2008; 136(3): 419-431.

Daitch D, Daitch J, Novinson D, et al.: Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Pain Med. 2014; 15(12): 2087-2094.

Gordon A, Callaghan D, Spink D, et al.: Buprenorphine transdermal system in adults with chronic low back pain: A randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase. Clin Ther. 2010; 32(5): 844-860.

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, openlabel, noninferiority analysis. Clin Ther. 2007; 29(5): 874-888.

Han C, Smolen JS, Kavanaugh A, et al.: The impact of infliximab treatment on quality of life in patients with inflammatory rheumatic diseases. Arthritis Res Ther. 2007; 9(5): R103.

Kimel M, Revicki D, Rao S, et al.: Norms-based assessment of patient-reported outcomes associated with adalimumab monotherapy in patients with ankylosing spondylitis. Clin Exp Rheumatol. 2011; 29(4): 624-632.

Miller K, Yarlas A, Wen W, et al.: Buprenorphine transdermal system and quality of life in opioid-experienced patients with chronic low back pain. Expert Opin Pharmacother. 2013; 14(3): 269-277.

Strand V, Kosinski M, Gnanasakthy A, et al.: Secukinumab treatment in rheumatoid arthritis is associated with incremental benefit in the clinical outcomes and HRQoL improvements that exceed minimally important thresholds. Health Qual Life Outcomes. 2014; 12: 31.

Wells G, Li T, Tugwell P: Investigation into the impact of abatacept on sleep quality in patients with rheumatoid arthritis, and the validity of the MOS-Sleep questionnaire Sleep Disturbance Scale. Ann Rheum Dis. 2010; 69(10): 1768-1773.

Yarlas A, Miller K, Wen W, et al.: A randomized, placebo-controlled study of the impact of the 7-day buprenorphine transdermal system on health-related quality of life in opioid-naïve patients with moderate-to-severe chronic low back pain. J Pain. 2013; 14(1): 14-23.

Yarlas A, Miller K, Wen W, et al.: Buprenorphine transdermal system improves sleep quality and reduces sleep disturbance in patients with moderate-to-severe chronic low back pain: Results from two randomized controlled trials. Pain Pract. January 20, 2015 (epub ahead of print).

Bergander B, Erdur L, Kallenbach-Dermutz B, et al.: Younger and older chronic somatoform pain patients in psycho-diagnostics, physician-patient relationship and treatment outcome. Biopsychosoc Med. 2013; 7(1): 4.

Chen L, Vo T, Seefeld L, et al.: Lack of correlation between opioid dose adjustment and pain score change in a group of chronic pain patients. J Pain. 2013; 14(4): 384-392.

Kalso E, Simpson KH, Slappendel R, et al.: Predicting long-term response to strong opioids in patients with low back pain: Findings from a randomized, controlled trial of transdermal fentanyl and morphine. BMC Med. 2007; 5: 39.

Hayek SM, Veizi IE, Narouze SN, et al.: Age-dependent intrathecal opioid escalation in chronic noncancer pain patients. Pain Med. 2011; 12(8): 1179-1189.

Karlsson J, Söderström A, Augustini BG, et al.: Is buprenorphine transdermal patch equally safe and effective in younger and elderly patients with osteoarthritis-related pain? Results of an age-group controlled study. Curr Med Res Opin. 2014; 30(4): 575-587.

Likar R, Vadlau E, Breschan C, et al.: Comparable analgesic efficacy of transdermal buprenorphine in patients over and under 65 years of age. Clin J Pain. 2008; 24(6): 536-543.

Micca JL, Ruff D, Ahl J, et al.: Safety and efficacy of duloxetine treatment in older and younger patients with osteoarthritis knee pain: A post hoc, subgroup analysis of two randomized, placebo-controlled trials. BMC Musculoskelet Disord. 2013; 14: 137.

Hale ME, Ahdieh H, Ma T, et al.: Efficacy and safety of OPANA ER (oxymorphone extended release) for relief of moderate to severe chronic low back pain in opioid-experienced patients: A 12-week, randomized, double-blind, placebo-controlled study. J Pain. 2007; 8(2): 175-184.

Katz N, Rauck R, Ahdieh H, et al.: A 12-week, randomized, placebo-controlled trial assessing the safety and efficacy of oxymorphone extended release for opioid-naive patients with chronic low back pain. Curr Med Res Opin. 2007; 23(1): 117-128.

Roland CL, Setnik B, Cleveland JM, et al.: Clinical outcomes during opioid titration following initiation with or conversion to Remoxy®, an extended-release formulation of oxycodone. Postgrad Med. 2011; 123(4): 148-159.

Bair MJ, Robinson RL, Katon W, et al.: Depression and pain comorbidity: A literature review. Arch Intern Med. 2003; 163(20): 2433-2445.

Bennett RM, Burckhardt CS, Clark SR, et al.: Group treatment of fibromyalgia: A 6 month outpatient program. J Rheumatol. 1996; 23(3): 521-528.

de Rooij A, Roorda LD, Otten, RH, et al.: Predictors of multidisciplinary treatment outcome in fibromyalgia: A systematic review. Disabil Rehabil. 2013; 35(6): 437-449.

Sorrell M, Flanagan W, McCall J: The effect of depression and anxiety on the success of multidisciplinary treatment of chronic resistant myofascial pain. J Musculoskelet Pain. 2003; 11(1): 17-20.

Yarlas A, Miller K, Wen W, et al.: A subgroup analysis found no diminished response to buprenorphine transdermal system treatment for chronic low back pain patients classified with depression. Pain Pract. April 11, 2015 (epub ahead of print).

de Rooij A, van der Leeden M, Roorda LD, et al.: Predictors of outcome of multidisciplinary treatment in chronic widespread pain: An observational study. BMC Musculoskelet Disord. 2013; 14: 133.

Gear RW, Miaskowski C, Gordon NC, et al.: The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain. Pain. 1999; 83(2): 339-345.

Pieh C, Altmeppen J, Neumeier S, et al.: Gender differences in outcomes of a multimodal pain management program. Pain. 2012; 153(1): 197-202.

Bartley EJ, Fillingim RB: Sex differences in pain: A brief review of clinical and experimental findings. Brit J Anaesth. 2013; 111(1): 52-58.

Fillingim RB, King CD, Ribeiro-Dasilva MC, et al.: Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009; 10(5): 447-485.

Niesters M, Dahan A, Kest B, et al.: Do sex differences exist in opioid analgesia? A systematic review and meta-analysis of human experimental and clinical studies. Pain. 2010; 151(1): 61-68.

Wen W, Sitar S, Lynch S, et al.: A multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of single-entity, once-daily hydrocodone tablets in patients with uncontrolled moderate to severe chronic low back pain. Expert Opin Pharmacother. 2015 (epub ahead of print).

Wen W, Taber L, Lynch SY, et al.: 12-Month safety and effectiveness of once-daily hydrocodone tablets formulated with abuse-deterrent properties in patients with moderate to severe chronic pain. J Opioid Manag. 2015 (in press).

Jaeschke R, Singer J, Guyatt GH: Measurement of health status: Ascertaining the minimal clinically important difference. Control Clin Trials. 1989; 10(4): 407-415.

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): 149-158.

Ostelo RW, Deyo RA, Stratford P, et al.: Interpreting change scores for pain and functional status in low back pain: Towards international consensus regarding minimal important change. Spine (Phila Pa 1976). 2008; 33(1): 90-94.

Salaffi F, Stancati A, Silvestri CA, et al.: Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale. Eur J Pain. 2004; 8(4): 283-291.

Cleeland CS, Ryan KM: Pain assessment: Global use of the Brief Pain Inventory. Ann Acad Med Singapore. 1994; 23(2): 129-138.

Dworkin RH, Turk DC, Wyrwich KW, et al.: Interpreting the clinical importance of treatment outcomes in chronic pain

clinical trials: IMMPACT recommendations. J Pain. 2008; 9(2): 105-121.

Maruish ME (ed.): User's Manual for the SF-36v2® Health Survey. 3rd ed. Lincoln, RI: QualityMetric Incorporated, 2011.

Maruish ME (ed.): User's Guide for the MOS Sleep Scale- Revised. Lincoln, RI: QualityMetric Incorporated, 2012.

Norman GR, Sloan JA, Wyrwich KW: Interpretation of changes in health-related quality of life: The remarkable universality of half a standard deviation. Med Care. 2003; 41(5): 582-592.

Norman GR, Sloan JA, Wyrwich KW: The truly remarkable universality of half a standard deviation: Confirmation through another look. Expert Rev Pharmacoecon Outcomes Res. 2004; 4(5): 581-585.

Agresti A, Coull BA: Approximate Is Better than “Exact” for Interval Estimation of Binomial Proportions. Am Stat. 1998; 52(2): 119.

Lynch S, Wen W, Taber L, et al.: Long-term safety and effectiveness of once-daily, single-entity, abuse-deterrent hydrocodone in chronic nonmalignant and nonneuropathic pain: Results of a long-term open-label study. J Pain. 2014; 15(4): S91.

Centers for Medicare & Medicaid Services: Medicare Part D Overutilization Monitoring System. 2014. Available at http://www.cms.gov/Medicare/Prescription-Drug-Coverage/PrescriptionDrugCovContra/Downloads/HPMSmemo_MedicarePartDOverutilizationMonitoringSystem011714.pdf. Accessed July 7, 2015.

Chou R, Fanciullo GJ, Fine PG, et al.: Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10(2): 113-130.

Agency Medical Directors Group: Interagency Guideline on Opioid Dosing for Chronic Non-Cancer Pain: An Educational Aid to Improve Care and Safety with Opioid Therapy. 2010. Available at http://www.agencymeddirectors.wa.gov/Files/OpioidGdline.pdf. Accessed July 7, 2015.