43 - Treatment outcomes in patients with postherpetic neuralgia: a controlled trial of capsaicin 8% patch versus oral pregabalin
Charles Argoff1, Marielle Eerdekens2 , Sylvia Engelen2, Lizandra Marcondes3
1Albany Medical Center, New York, NY, USA. 2Grünenthal GmbH, Aachen, Germany. 3Grünenthal Inc., Morristown, NJ, USA
Purpose Postherpetic neuralgia (PHN) is the most common complication of shingles. It continues to be a prevalent peripheral neuropathic pain (PNP) condition, despite the availability of a variety of pharmacological interventions (Hadley et al., 2016).1 In addition to pain, the disorder is associated with impaired functionality and quality of life. Pregabalin (PRE) is one of the established first line treatments for use in PHN whereas the high concentration 8% capsaicin patch (HCCP) is commonly recommended as a second line therapy. 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. The goal of this investigation was to compare treatment outcomes of HCCP and PRE in a subgroup of patients with PHN from ELEVATE (primary data and safety/tolerability data have been presented previously by Haanpää et al., 2016).2 Methods The ELEVATE study was an open-label, randomized, multicenter, non-inferiority trial. Eligible patients with PHN had pain persisting for at least 6 months after shingles vesicle crusting, and were either naïve to, or, in the opinion of the investigator had not received adequate pain relief with, gabapentin or pregabalin. The study participants were randomly assigned 1:1 to a single treatment with the HCCP (179mg (8% w/w)) or to optimized daily treatment with pregabalin (75mg capsules), the study lasted 8 weeks. Subjects were assessed at baseline and predefined times throughout the study using the following rating scales: Numeric Pain Rating Scale (NPRS); maximum Neuropathic Pain Symptom Inventory (NPSI) subscales [burning (superﬁcial) spontaneous pain, pressing (deep) spontaneous pain, paroxysmal pain, evoked pain, paraesthesia/dysesthesia]; Treatment Satisfaction Questionnaire for Medication (TSQM); EuroQol-5D (EQ-5D); Patient Global Impression of Change (PGIC); and Medical Outcomes Study-6 item questionnaire for cognitive function and sleep (MOS). The area of dynamic mechanical allodynia (ADMA) was measured, and adverse events were monitored. The primary efficacy parameter was defined as a ≥30% reduction from baseline in the average pain score over a 24-hour period based on the NPRS score. The optimal therapeutic effect was defined as no change in concomitant chronic pain medication, no discontinuation of the HCCP application or trial medication due to lack of efficacy or tolerability prior to the end of study (EoS), ≥30% reduction in NPRS pain score for ≥4 consecutive days between baseline and EoS, and no moderate or serious adverse reactions during the stable treatment period. Post hoc analyses with logistic regression models were used, with baseline observation carried forward (BOCF) analyses to account for missing data. Results In the ELEVATE study 136 patients had PHN and were randomized to each group, 63 participants received treatment with HCCP and 73 received oral pregabalin. In the two different treatment groups, 71.4% of patients were responders in the HCCP group compared with 76.7% in the pregabalin group (difference: -5.3%, 95% CI: -20.1%, +9.5%). In terms of the optimal response, the numbers were 71.4% versus 63.0%, respectively (difference: +8.4%, 95%: -7.3%, +24.1%). The secondary efficacy assessments evaluated for the two treatment groups included: NPRS pain responses, NPSI subscale responses, patient satisfaction with treatment (TSQM), quality of life (EQ-5D), and the Patient Global Impression of Change (PGIC). Specifically, the total NPSI score decreased with a mean (SD) of -56.4 (40.48) and -47.0 (42.47) for HCCP and PRE, respectively. On the TSQM scale, outcomes were generally similar between the two treatment groups with the exception of the side effects scale where scores were higher favoring HCCP (91.6) over PRE (78.8) with a LS Mean Difference of 12.8 (95% Cl: 5.2, 20.4). The EQ-5D-5L scores increased with an absolute mean (SD) change of 17.2 (19.65) and 13.7 (19.75) for HCCP and PRE, respectively. On the PGIC, 69.8% vs 57.7% patients reported to be very much or much improved with HCCP and PRE, respectively. The mean (SD) change on the MOS scale was 5.4 (9.87) versus 0.7 (10.70) for HCCP and PRE respectively with a LS mean difference (95% Cl) of 5.7 (2.8, 8.6). The mean (SD) reduction of area of dynamic mechanical allodynia was -162.9 (213.93) cm2 and -73.2 (269.7) cm2 with HCCP and PRE, respectively. In total, the % days (mean (SD)) free from any treatment emergent adverse events (TEAEs) were 89.1 (23.04) % and 74.8 (35.18) % with HCCP and PRE, respectively. Approximately two-thirds of patients achieved pain relief within 7 days with HCCP, versus only one-third of patients with PRE. TSQM scale outcomes were generally similar between the two treatments, with the exception of the side effects scale which showed better patient satisfaction in the HCCP treatment group. Furthermore, HCCP provided an optimal therapeutic response in more patients than PRE, and it produced better outcomes on the MOS 6 item questionnaire for cognitive function and sleep, as well as the response to ADMA. Conclusions PHN is a complex disorder that can significantly impact patient functioning and quality of life. In this randomized controlled trial, HCCP treatment outcomes compared favorably with PRE in patients with PHN. The proportion of patients with a ≥30% reduction in NPRS score (primary response) was equivalent between treatments, whilst more patients had an optimal response in the HCCP group. The mean TSQM side effects score was better with the HCCP, and fewer patients discontinued treatment because of treatment-related adverse events. In addition, the onset of pain relief was quicker and there was a greater reduction in ADMA. Treatment with the HCCP provided an optimal therapeutic effect in more patients, led to better outcomes on the MOS cognitive functioning scale, provided a quicker onset of pain relief and more prominently reduced the ADMA with improved tolerability (higher % of days free from TEAEs) than treatment with PRE. The outcomes of this head-to-head study show that the HCCP has non-inferior efficacy to oral PRE, allowing for patient preference and involvement when selecting single or combined therapies for chronic PNP conditions.