Class Update: Neuropathic Pain

Transcription

1 Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon Phone Fax I. EXECUTIVE SUMMARY: Month/Year of Review: February 2012 Last Oregon Review: March 2008 (DERP Systematic Review) Class Update: Neuropathic Pain Reason for Review: The Oregon Evidence-based Practice Center (EPC) for the Drug Effectiveness Review Project (DERP) produced an updated report for the Neuropathic Pain Drug Class Review which was published in June of The full report can be found on the Evidence-based Practice Center website: and the final executive summary can be found on the Oregon Pharmacy and Therapeutics website: This report will be evaluated and summarized for any potential Oregon Health Plan policy decisions. Refer to the full reports for details on methods, search strategy, inclusion criteria, outcomes included, and methods for grading the evidence. In addition, the FDA approved a new once daily formulation of gabapentin ER (GRALISE ) for the treatment of post-herpetic neuralgia and the capsaicin 8% patch (Qutenza) for post-herpetic neuralgia 2, 3. These drugs were not included in the review by the Oregon EPC. Key Questions 1 : What is the comparative effectiveness of anticonvulsants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), and the lidocaine patch for neuropathic pain? What are the comparative harms of anticonvulsants, tricyclic antidepressants, SNRIs, and the lidocaine patch for neuropathic pain? Are there differences in effectiveness or harms of anticonvulsants, tricyclic antidepressants, SNRIs, and the lidocaine patch based on demographics, socioeconomic status, comorbidities, or drug-drug interactions, when used to treat neuropathic pain? Summary: Current strategies for the treatment of neuropathic pain include oral anticonvulsants, serotonin-norepinephrine reuptake inhibitors (SNRI s), tricyclic antidepressants (TCAs), and topical analgesics 1. Current OHP management of these drugs includes prior authorization criteria restricting approval of pregabalin only if the client has previously tried or is contraindicated to gabapentin and either a TCA or oral carbamazepine. The DERP update 1

2 compared the effectiveness and safety of all these drugs excluding the extended release gabapentin (Gralise) and capsaicin 8% patch (Qutenza). Simple analgesics and opioids were also not included in the review. Overall, the current comparative evidence for neuropathic pain is limited. Of the 128 studies included in the DERP report, only 14 were direct comparisons of drugs and the majority of included studies were small and of a relatively short duration 1. The DERP review of the available evidence concludes the following regarding comparative effectiveness and harms: Effectiveness 1 : The majority of direct evidence was in patients with diabetic neuropathy and postherpetic neuralgia. Based on small studies in these populations, there is moderate-strength evidence that there is no significant difference between gabapentin, pregabalin, and lamotrigine compared with TCA s in the rate of response and low-strength evidence that there is also no significant difference between lidocaine 5% patch and pregabalin. Based only on indirect comparisons, there is low strength evidence that duloxetine, pregabalin, and gabapentin are superior to lacosamide and lamotrigine, and pregabalin appears to be superior to topiramate. There is no direct evidence evaluating treatment with divalproex, oxcarbazepine, and topiramate. There is very limited comparative evidence evaluating efficacy in patients with other types of neuropathic pain and it was not possible to conduct indirect analyses due to significant differences among study designs and outcomes. There was 1 direct comparative trial each of patients with central post stroke pain, spinal cord injury, polyneuropathy, and cancer. Harms 1 : In patients with diabetic neuropathy and postherpetic neuralgia, moderate-strength evidence shows there is no significant difference in withdrawals due to adverse events between gabapentin, pregabalin, and lamotrigine compared with amitriptyline and nortriptyline, but greater with oral pregabalin compared to the 5% lidocaine patch. Using only indirect comparisons, low-strength evidence supports no significant difference with withdrawals due to adverse events between duloxetine, pregabalin, lacosamide, and lamotrigine. There is insufficient direct evidence to evaluate comparative harms in other types of neuropathic pain. Guidelines In 2010 The National Institute for Health and Clinical Excellence (NICE) published guidelines for the treatment of neuropathic pain in the non-specialist setting and recommended amitriptyline or pregabalin as first-line treatment and duloxetine or amitriptyline first line in patients with painful diabetic neuropathy 4. Since those there were significant concerns about the associated costs with pregabalin as a first line agent for adults with neuropathic pain and an updated guideline document is anticipated to be available in The provisional draft recommendations are currently published and state that oral amitriptyline or gabapentin are recommended as first-line agents for neuropathic conditions due to similar efficacy and an added cost benefit. Pregabalin is recommended as an alternative to gabapentin if patients cannot adhere to the dosing schedules or tolerate adverse events 5. The American Academy of Neurology recently published evidence-based guidelines for the treatment of painful diabetic neuropathy and concluded that pregabalin is established as effective based on evidence displaying pain relief and venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, 2

3 and capsaicin cream are probably effective for treatment of painful diabetic neuropathy 6. This evidence-based systematic review also found a low strength of evidence that the lidoderm patch is possibly effective. There is limited data for the effectiveness of carbamazepine and what does exist is very dated. However, current guidelines still recognize that carbamazepine has been the routine treatment for trigeminal neuralgia in clinical practice and due to lack of good-quality evidence for treating trigeminal neuralgia, continue to recommend carbamazepine in treating trigeminal neuralgia. 4, 7 Additional Available Treatment The approval of gabapentin ER (Gralise) was based on one short-term placebo-controlled study that showed a statistically significant improvement in mean pain score compared to placebo in patients with postherpetic neuralgia. This is a new preparation of gabapentin with a delivery system allowing for once-daily dosing 3, 8. There is a lack of data supporting its efficacy, safety, and optimal dosing and no comparative effectiveness data with any other treatments for postherpetic neuralgia. The capsaicin 8% patch (Qutenza) is the first product to contain prescription strength capsaicin for the management of neuropathic pain associated with postherpetic neuralgia. The capsaicin patch was approved based on two randomized low-dose controlled trials in patients with postherpetic neuralgia that were required to of had at least 6 months of oral treatment. 9 There were significantly more patients taking concomitant drugs for neuropathic pain in the treatment group (50% vs. 38%, p=0.021) in one study. These two studies showed that compared to a low-dose capsaicin (0.04%) control patch, capsaicin 8% had a statistically significant greater percent change of pain score from baseline although the clinical significance of the difference is low (less than a 2 point reduction in patient-reported pain). Due to the potential irritation caused by the high strength capsaicin and administration site reactions, the patch has to be administered by a health care professional and would likely require specialist administration. There is a low quality of evidence demonstrating that capsaicin 0.075% cream is probably effective for the treatment of diabetic neuropathy and is 4, 10 recommended for consideration in the evidence-based guidelines by the American Academy of Neurology and is evaluated in the NICE guidelines. Conclusions: Overall there is low to moderate evidence comparing benefits and harms of available drugs for neuropathic pain. The majority of available direct comparative evidence is in patients with either diabetic neuropathy or postherpetic neuralgia and included comparisons between amitriptyline or nortriptline and gabapentin, pregabalin, or lamotrigine. There is insufficient comparative effectiveness evidence in patients with other types of neuropathic pain to assess comparative safety and conclusions for efficacy were largely based from placebo-controlled trials and indirect analyses 1. In patients with diabetic neuropathy and postherpetic neuralgia, there is moderate evidence that there is not a statistically significant difference in response or withdrawal due to adverse events with gabapentin, pregabalin, and lamotrigine compared to tricyclic antidepressants and low strength 3

4 evidence that there is no difference between oral pregabalin and the lidocaine patch. Low strength evidence based on indirect comparisons demonstrates that duloxetine, pregabalin, and gabapentin are superior to lacosamide and lamotrigine and there are no differences between pregabalin, duloxetine, and gabapentin or comparisons of lidocaine and amitriptyline or gabapentin 1. Recommendations: Include topical analgesics into current neuropathic pain PA criteria including Lidoderm patch and capsaicin 8% patch to restrict use to patients with postherpetic neuralgia who have failed or cannot tolerate oral therapy with gabapentin and TCA s. Designate gabapentin ER as a line extension of currently available gabapentin and as a non-preferred agent due no management demonstrated in evidence-based guidelines and alternative therapy with available comparative effectiveness evidence showing efficacy in neuropathic pain. 4

5 References 1. Selph S, Carson S, Thakurta S, Low A, McDonagh M. Drug Class Review: Neuropathic Pain. Update 1 final report. Prepared by the Oregon Evidencebased Practice Center for the Drug Effectiveness Review Project. Oregon Health and Science University. Portland, OR Available at: 2. Qutenza Package Insert. Available at: 3. Gralise Package Insert. Available at: 4. Centre for Clinical Practice. Neuropathic pain. The pharmacological management of neuropathic pain in adults in non-specialist settings. London (UK): National Institute for Health and Clinical Excellence (Nice) Centre for Clinical Practice. Neuropathic pain. The pharmacological management of neuropathic pain in adults in non-specialist settings. Draft Consultation. London (UK): National Institute for Health and Clinical Excellence (Nice) Bril V, England J, Franklin G m., et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Neurology. 2011;76(20): Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur. J. Neurol. 2010;17(9):1113-e Wallace MS, Irving G, Cowles VE. Gabapentin extended-release tablets for the treatment of patients with postherpetic neuralgia: A randomized, double-blind, placebo-controlled, multicentre study. Clinical Drug Investigation. 2010;30(11): Food and Drug Administration Center for Drug Evaluation and Research. Summary Review. Application Number Available at: Food and Drug Administration Center for Drug Evaluation and Research. 10. Bril V, England J, Franklin G m., et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Neurology Available at: Accessed December 16,