Pregabalin for Neuropathic Pain and Itch in Recessive Dystrophic Epidermolysis Bullosa: A Randomized Crossover Trial

Abstract

Importance: Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB.

Objectives: To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB.

Design, setting, and participants: A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the Douleur Neuropathique 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023.

Intervention: Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups.

Main outcomes and measures: Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention.

Results: In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated.

Conclusions and relevance: The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial.

Trial registration: ClinicalTrials.gov Identifier: NCT03928093.

Figure 1.. Flow Diagram of Participants With RDEB

Forty-one eligible patients (8-40 years old) with a primary diagnosis of RDEB were contacted by the 2 study centers (Canada and Chile). After screening for neuropathic pain and indicating a willingness to participate, 10 participants (26% of eligible patients) were allocated to either group 1 (n = 6) to start flexible-dose pregabalin (50-300mg/d) followed by placebo, or to group 2 to start flexible-dose placebo followed by flexible-dose pregabalin. RDEB indicates recessive dystrophic epidermolysis bullosa.

Figure 2.. Pain and Itch Scores According to Intervention Group and Treatment

Pain (A) and itch (B) mean levels measured with a 10-point VAS at baseline and at the end of each treatment (pregabalin or placebo) in both groups (group 1, pregabalin followed by placebo; group 2, placebo followed by pregabalin); whiskers indicated 95% CIs. Pain (C) and itch (D) reduction by participant (difference in VAS before and after treatment; pooled data from group 1 and group 2). VAS indicates visual analog scale.