Switching From Pregabalin to Mirogabalin in Patients with Peripheral Neuropathic Pain: A Multi-Center, Prospective, Single-Arm, Open-Label Study (MIROP Study)

Abstract

Introduction: Mirogabalin, which is a selective ligand of the α₂δ subunit of voltage-gated Ca²⁺ channels, was recently approved in Japan for peripheral neuropathic pain. The α₂δ ligands, including mirogabalin and pregabalin, are associated with significant risk of adverse events (AEs) such as somnolence or dizziness, leading to poor compliance and subsequent inefficacy. Safety and efficacy data for switching patients from pregabalin to mirogabalin are scarce.

Methods: This prospective, single-arm, open-label study involving ten participating centers in Japan recruited patients aged ≥ 20 years with peripheral neuropathic pain [visual analog scale (VAS) score ≥ 40 mm]. Where necessary, patients underwent a 1-week tapering period to reduce their pregabalin dose, after which pregabalin was stopped and mirogabalin dose was increased using a step-wise dose titration. Patients underwent dose increases after the first and second weeks if there were no tolerability issues, followed by the effective doses until the end of the study (4 weeks). The primary endpoint was the incidence of somnolence, dizziness, and peripheral edema; secondary endpoints included changes in VAS score. AEs were monitored for safety.

Results: Of 157 patients who provided informed consent, 152 patients were enrolled; 136 (89.5%) patients completed the study. The overall incidences of somnolence, dizziness, and peripheral edema were 41.4, 15.8, and 2.6%, respectively. Most patients (> 70%) experienced mild AEs, and one patient experienced a severe AE (dizziness). Most patients (> 70%) were able to achieve dose titration to an effective dose. Overall mean VAS score significantly decreased (Δ15.7 mm, p < 0.0001) by the end of the study.

Conclusions: Mirogabalin switching from pregabalin is well tolerated and effective in pain management for peripheral neuropathic pain using a step-wise titration.

Trial registration: Japan Registry of Clinical Trials (jRCTs031190113).

Keywords: Mirogabalin; Peripheral neuropathic pain; Pregabalin; Switching; α2δ ligands.

Fig. 1

Study design. ^a ± 7 days; i.e., dose-adjustment period could begin anywhere between days 9 and 22. ^b ± 7 days; i.e., end of study occurred anywhere between days 22 and 36. BID twice daily, CrCL creatinine clearance

Fig. 2

Patient disposition. ^aPatients may have had multiple reasons for withdrawal

Fig. 3

Cumulative incidence of somnolence, dizziness, and peripheral edema (safety analysis set; N = 152)

Fig. 4

Pain intensity (VAS score) from study enrollment to end of study (efficacy analysis set; N = 151). Data are mean ± standard deviation. ^a ± 7 days; i.e., dose-adjustment period could begin anywhere between days 9 and 22. ^b ± 7 days; i.e., end of study occurred anywhere between days 22 and 36. ***p < 0.001 vs. baseline using a paired t test. VAS visual analog scale