1Kansas Pain Management, Overland Park, KS, USA. 2Grünenthal GmbH, Aachen, Germany. 3Grünenthal Inc., Morristown, NJ, USA
Purpose Post-surgical neuropathic pain (PSNP) is peripheral neuropathic pain (PNP) following surgery. Managing patients with PNP is challenging as it often becomes chronic, with marked long-term reductions in health-related quality of life, decreased individual productivity and increased patient and healthcare expenditure. Etiologies range from mechanical and inflammatory diseases to injury and nerve compression. A key pathophysiological mechanism is neuronal hyperexcitability, both within the axon and cell body as well as at the peripheral nociceptors. This allows for single or combined therapies targeting one or more sites within the neuron. Treatments for PNP include systemic and local treatments such as pregabalin (PRE) or the high concentration 8% capsaicin patch (HCCP). PRE reduces neuronal excitability in the central nervous system by reversibly binding alpha-2-delta subunits of the Ca++ channels, thus reducing synaptic neurotransmitter release. Locally applied HCCP for 60-min rapidly delivers capsaicin into the skin directly targeting the nociceptor leading to its defunctionalization. HCCP is indicated for the treatment of peripheral neuropathic pain (PNP) in the EU and for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN) and for neuropathic pain associated with diabetic peripheral neuropathy (DPN) of the feet in the US.PSNP is a common yet underdiagnosed PNP condition with a high growing need for symptomatic treatments. In a recent placebo-controlled trial in patients with post-traumatic neuropathic pain (including patients with PSNP), pregabalin failed to meet the primary endpoint (change from baseline to week 15 on the numeric pain rating scale (NPRS) whereas key secondary endpoints yielded positive result (Markman et al. 2018).1 To date, no direct comparison of the efficacy of the HCCP and PRE in PSNP have been reported. In this post-hoc analysis in a subgroup of patients with PSNP from ELEVATE, treatment outcomes of HCCP and PRE are compared (primary and safety/tolerability data published in Haanpää et al., 2016).2 Methods In an eight-week open-label, randomized, multicenter, non-inferiority trial eligible patients with PSNP were randomly assigned 1:1 to a single treatment of the HCCP (179mg (8% w/w)) or to optimized daily treatment of pregabalin (75mg capsules), the study lasted 8 weeks. Efficacy assessments included the Numeric Pain Rating Scale (NPRS), Neuropathic Pain Symptom Scale (NPSI), Treatment satisfaction Questionnaire for Medication (TSQM), EQ-5D, Patient Global Impression of Change (PGIC), Area of Dynamic Mechanical Allodynia (ADMA). The proportion of patients in each arm who achieved ≥30% decrease in the ‘average pain for the past 24 hours’ NPRS score was assessed from baseline to Week 8. The results pertain to a post-hoc analysis using analysis of covariance models, and Least Square means are presented. Baseline observation carried forward (BOCF) analyses were used to account for missing data. Secondary endpoints included optimal therapeutic effect (OTE), time-to-onset of pain relief and treatment satisfaction. Results In the ELEVATE study 145 patients had PSNP and were randomized to each group, 78 participants received treatment with HCCP and 67 received oral pregabalin. At the end of week 8, respectively 48.7% and 31.3% were responders (≥30% decrease in NPRS from baseline) and 46.2% versus 22.6% were very much or much improved on the PGIC. HCCP treatment scored higher than PRE on TQSM (68.7 versus 43.8 on global satisfaction). The total NPSI score decreased (-35.1 and -27.0 for HCCP and PRE, respectively) whereas the EQ-5D-5L scores increased (15.3 and 4.3, respectively). The ADMA was reduced by 78.9 cm2 and 63.5 cm2, respectively. Conclusions A single treatment with HCCP compared favorably with daily oral pregabalin in PSNP patients considering responder rates, patient assessment of improvement, patient satisfaction and reduction of ADMA.