Effect of pregabalin on dynamic allodynia in patients with postherpetic neuralgia (PHN): Results from a double-blind, randomized, controlled trial (RCT)

Although common in patients with PHN (>50%), dynamic allodynia has not been routinely evaluated in large RCTs. We evaluated the effect of pregabalin, an alpha-2-delta ligand, on Visual Analog Scale (VAS) ratings of dynamic (brush-evoked) allodynia in PHN in this placebo-controlled RCT. The study consisted of a 7-day screening period, 28-day treatment phase, and 1-week taper. Patients (≥18y) with PHN for 3 months, pain VAS score of 40mm (100-mm scale), who completed the daily pain NRS ≥4 times (average daily score 4; 0-10 scale) during 7-day screening. Time-to-onset of clinically meaningful pain relief (1-point improvement in daily pain score in patients achieving ≥30% decrease in weekly pain score at endpoint) was the primary efficacy measure, with VAS allodynia being a secondary measure and the focus of this analysis. A total of 91 patients were randomized to flexible-dosage pregabalin (optimized dose 150-600mg/d BID); 88 to fixed-dosage 300mg/d; and 90 to placebo for 4 weeks. Median time-to-onset of pain relief was 3.5d, 1.5d, and >4wks for flexible, fixed, and placebo, respectively and corresponded to meaningful pain relief achieved in 69.2%, 58.0%, and 30% of treatment groups, respectively. Fixed- and flexible-dosage pregabalin appeared superior to placebo as early as Days 1 and 2, respectively. Most patients (approx. 66%) had moderate-to-severe allodynia at baseline. Baseline-to-endpoint LS-mean changes in brush-evoked allodynia in PHN-affected areas for flexible-, fixed-dosage, and placebo groups were: −26.23 (P<0.0001) −20.81 (P=0.0075), and −11.83. Significant improvement of pregabalin over placebo was seen at Week 1. Endpoint improvement in allodynia correlated with improvement in pain for all groups. Improvements in mean weekly pain score and brush-evoked allodynia rating significantly correlated with improvement on PGIC. Both pregabalin regimens were well-tolerated. Both pregabalin regimens were associated with early-onset clinically meaningful, sustained pain relief and corresponding improvements in dynamic allodynia and PGIC scores in PHN patients.