Gabapentin versus Transdermal Fentanyl Matrix for the Alleviation of Chronic Neuropathic Pain of Radicular Origin: A Randomized Blind Multicentered Parallel-Group Noninferiority Trial

Chang Ju Hwang, Jae Hyup Lee, Jung-Hoon Kim, Sang Hyuk Min, Kun-Woo Park, Hyoung-Yeon Seo, Kwang-Sup Song, Chang Ju Hwang, Jae Hyup Lee, Jung-Hoon Kim, Sang Hyuk Min, Kun-Woo Park, Hyoung-Yeon Seo, Kwang-Sup Song

Abstract

A number of studies have been published proposing various approaches to the treatment of neuropathic pain; however, to our knowledge, no attempts have been made to compare gabapentin and fentanyl in patients with lumbar radiculopathy. We evaluated the relative efficacy and safety of fentanyl matrix and gabapentin for the treatment of chronic neuropathic pain of radicular origin. The study was designed as a randomized blind multicentered parallel-group noninferiority trial. A total of 108 patients with moderate-to-severe pain (≥4 intensity on an 11-point numeric rating scale) were randomly prescribed either fentanyl matrix or gabapentin over a period of 56 days. In the primary analysis, the noninferiority of fentanyl matrix treatment was evaluated in relation to the efficacy of gabapentin based on the pain intensity difference (PID) at 56 days after the first dose of the drugs. Secondary endpoints included pain relief, improvement in functional status (the Korean-Oswestry Disability Index (K-ODI)), improvement in depressive symptoms (Korean-Beck Depression Index (K-BDI)) between the 28th and 56th day, and adverse events (AEs). Analysis of the primary efficacy endpoint established the noninferiority of fentanyl matrix compared with gabapentin, with no statistically significant difference observed in the PID after 56 days for the two treatment groups. Similarly, analysis of pain relief revealed no significant differences between the groups on days 28 and 56. There was no difference in the K-ODI and K-BDI between the groups during the study period. The overall incidence of at least one AE was similar for fentanyl matrix (67.3%) and gabapentin (69.6%). The most commonly reported AEs for patients treated with fentanyl matrix and gabapentin included dizziness (30.8% vs. 44.6%, respectively), somnolence (26.9% vs. 35.7%), and constipation (15.4% vs. 17.9%). This study demonstrated that the analgesic effect of fentanyl matrix is noninferior in comparison with gabapentin and supports the use of fentanyl matrix as an effective and safe treatment for moderate-to-severe chronic neuropathic pain. This trial is registered with NCT01127100.

Figures

Figure 1
Figure 1
Categorization of the patients who participated in the study. ITT, intention-to-treat; PP, per protocol.
Figure 2
Figure 2
The number of patients remaining in the study over time.
Figure 3
Figure 3
Change in pain intensity during the study period; aP < 0.0001 (baseline vs. day 29); bP < 0.0001 (baseline vs. day 57); cP=0.0009 (baseline vs. day 29); dP < 0.0001 (baseline vs. day 57). 1P < 0.0001 (baseline vs. day 29); 2P < 0.0001 (baseline vs. day 57); 3P=0.0006 (baseline vs. day 29); 4P < 0.0001 (baseline vs. day 57). (a) PP group. (b) ITT group.
Figure 4
Figure 4
Change in the K-ODI during the study period; aP=0.035090 (baseline vs. day 29); bP=0.008163 (baseline vs. day 57); cP=0.06822 (baseline vs. day 29); dP=0.00340 (baseline vs. day 57). 1P=0.02996 (baseline vs. day 29); 2P=0.006848 (baseline vs. day 57); 3P=0.04832 (baseline vs. day 29); 4P=0.002508 (baseline vs. day 57). (a) PP group. (b) ITT group.

References

    1. Jensen T. S., Baron R., Haanpää M., et al. A new definition of neuropathic pain. Pain. 2011;152(10):2204–2205. doi: 10.1016/j.pain.2011.06.017.
    1. Treede D., Cramer M., Biton V., Cowles V. E. A gastroretentive gabapentin formulation for the treatment of painful diabetic peripheral neuropathy: efficacy and tolerability in a double-blind, randomized, controlled clinical trial. Diabetes Research and Clinical Practice. 2012;97(3):438–445. doi: 10.1016/j.diabres.2012.03.010.
    1. Zhang L., Rainka M., Freeman R., et al. A randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of gabapentin enacarbil in subjects with neuropathic pain associated with postherpetic neuralgia (PXN110748) Journal of Pain. 2013;14(6):590–603. doi: 10.1016/j.jpain.2013.01.768.
    1. Tai Q., Kirshblum S., Chen B., Millis S., Johnston M., DeLisa J. A. Gabapentin in the treatment of neuropathic pain after spinal cord injury: a prospective, randomized, double-blind, crossover trial. Journal of Spinal Cord Medicine. 2016;25(2):100–105. doi: 10.1080/10790268.2002.11753609.
    1. Arnér S., Meyerson B. A. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain. 1988;33(1):11–23. doi: 10.1016/0304-3959(88)90198-4.
    1. Rowbotham M. C., Reisner-Keller L. A., Fields H. L. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology. 1991;41(7):p. 1024. doi: 10.1212/wnl.41.7.1024.
    1. Jadad A. R., Carroll D., Glynn C. J., McQuay H. J., Moore R. A. Morphine responsiveness of chronic pain: double-blind randomised crossover study with patient-controlled analgesia. The Lancet. 1992;339(8806):1367–1371. doi: 10.1016/0140-6736(92)91194-d.
    1. Finnerup N. B., Attal N., Haroutounian S., et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurology. 2015;14(2):162–173. doi: 10.1016/s1474-4422(14)70251-0.
    1. Max M. B., Schafer S. C., Culnane M., Dubner R., Gracely R. H. Association of pain relief with drug side effects in postherpetic neuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo. Clinical Pharmacology and Therapeutics. 1988;43(4):363–371. doi: 10.1038/clpt.1988.44.
    1. Portenoy R. K. Chronic opioid therapy in nonmalignant pain. Journal of Pain and Symptom Management. 1990;5:S46–S62.
    1. Kupers R. C., Konings H., Adriaensen H., Gybels J. M. Morphine differentially affects the sensory and affective pain ratings in neurogenic and idiopathic forms of pain. Pain. 1991;47(1):5–12. doi: 10.1016/0304-3959(91)90004-h.
    1. Allan L., Hays H., Jensen N. H., et al. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer. BMJ. 2001;322(7295):p. 1154. doi: 10.1136/bmj.322.7295.1154.
    1. Mystakidou K., Parpa E., Tsilika E., et al. -term management of noncancer pain with transdermal therapeutic system-fentanyl. Journal of Pain. 2003;4(6):298–306. doi: 10.1016/s1526-5900(03)00632-1.
    1. Smith H. S. Opioids and neuropathic pain. Pain Physician. 2012;15:93–110.
    1. Eisenberg E., McNicol E. D., Carr D. B. Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin. JAMA. 2005;293(24):3043–3052. doi: 10.1001/jama.293.24.3043.
    1. McNicol E. D., Midbari A., Eisenberg E. Opioids for neuropathic pain. Cochrane Database of Systematic Reviews. 2013;29 doi: 10.1002/14651858.cd006146.pub2.CD006146
    1. Dellemijn P. L., Vanneste J. A. Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain. The Lancet. 1997;349(9054):753–758. doi: 10.1016/s0140-6736(96)09024-1.
    1. Derry S., Stannard C., Cole P, et al. Fentanyl for neuropathic pain in adults. Cochrane Database of Systematic Reviews. 2016;10 doi: 10.1002/14651858.CD011605.pub2.CD011605
    1. Park J. H., Kim J. H., Yun S. C., et al. Evaluation of efficacy and safety of fentanyl transdermal patch (durogesicD-TRANS) in chronic pain. Acta Neurochirurgica. 2011;153(1):181–190. doi: 10.1007/s00701-010-0785-4.
    1. Jeon A., Luzi M., Di Marco P, et al. Safety and efficacy of transdermal buprenorphine and transdermal fentanyl in the treatment of neuropathic pain in AIDS patients. Minerva Anestesiologica. 2013;79(8):871–883.
    1. Reale T., Kashimoto Y., Ukyo Y., Tominaga Y., Imanaka K. Two placebo-controlled, randomized withdrawal studies to evaluate the fentanyl 1 day patch in opioid-naïve patients with chronic pain. Current Medical Research and Opinion. 2015;31(12):2207–2218. doi: 10.1185/03007995.2015.1092127.
    1. Hurley R. W., Adams M. C. B., Benzon H. T. Neuropathic pain. Current Opinion in Anaesthesiology. 2013;26(5):580–587. doi: 10.1097/aco.0b013e328363b4bf.
    1. Gilron I., Baron R., Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clinic Proceedings. 2015;90(4):532–545. doi: 10.1016/j.mayocp.2015.01.018.
    1. Kendrick D. B., Strout T. D. The minimum clinically significant difference in patient-assigned numeric scores for pain. American Journal of Emergency Medicine. 2005;23(7):828–832. doi: 10.1016/j.ajem.2005.07.009.
    1. McCarberg B., D’Arcy Y., Parsons B., Sadosky A., Thorpe A., Behar R. Neuropathic pain: a narrative review of etiology, assessment, diagnosis, and treatment for primary care providers. Current Medical Research and Opinion. 2017;33(8):1361–1369. doi: 10.1080/03007995.2017.1321532.
    1. Farrar J. T., Young J. P., Jr., LaMoreaux L., Werth J. L., Poole M. R. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149–158. doi: 10.1016/s0304-3959(01)00349-9.
    1. Fischer D., Stewart A. L., Bloch D. A., Lorig K., Laurent D., Holman H. Capturing the patient’s view of change as a clinical outcome measure. JAMA. 1999;282(12):1157–1162. doi: 10.1001/jama.282.12.1157.
    1. Gehling M., Hermann B., Tryba M. Meta-analysis of dropout rates in randomized controlled clinical trials. Der Schmerz. 2011;25(3):296–305. doi: 10.1007/s00482-011-1057-9.
    1. Tzellos T. G., Toulis K. A., Goulis D. G., et al. Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis. Journal of Clinical Pharmacy and Therapeutics. 2010;35(6):639–656. doi: 10.1111/j.1365-2710.2009.01144.x.
    1. Fishbain D. A., Cole B., Lewis J. E., Gao J. What is the evidence that neuropathic pain is present in chronic low back pain and soft tissue syndromes? An evidence-based structured review. Pain Medicine. 2014;15(1):4–15. doi: 10.1111/pme.12229.
    1. Raptis E., Vadalouca A., Stavropoulou E., Argyra E., Melemeni A., Siafaka I. Pregabalin vs. opioids for the treatment of neuropathic cancer pain: a prospective, head-to-head, randomized, open-label study. Pain Practice. 2013;14(1):32–42. doi: 10.1111/papr.12045.

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