Efficacy and Safety of Mirogabalin as an Add-on to Nonsteroidal Anti-inflammatory Drugs for Neuropathic Pain Caused by Lumbar Disc Herniation: A Randomized Controlled Study (Miro-Hers).

Introduction: Lumbar disc herniation (LDH) is characterized by the displacement of intervertebral disc material with compression of adjacent nerve roots, leading to nociceptive and neuropathic pain in the lower limbs and lower back. The Miro-Hers study explored the efficacy and safety of mirogabalin add-on treatment in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) compared with NSAIDs alone. We hypothesized that mirogabalin added on to NSAID therapy may reduce neuropathic pain due to LDH more than NSAIDs alone.

Methods: This was a multicenter, 8-week, randomized (1:1), open-label, parallel-group study conducted in Japan between March 2023 and September 2024. The study included participants with LDH diagnosed by magnetic resonance imaging who had inadequately controlled lower limb pain [numerical rating scale (NRS) score ≥ 4] despite NSAID treatment. The primary endpoint was the change in the NRS score for lower limb pain from baseline to Week 8. The secondary endpoints included quality of life, as assessed by the EuroQol 5 dimensions 5-level score (EQ-5D-5L), and NRS score for sleep disturbance. Safety endpoints included treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs).

Results: Of the 182 participants screened and randomized, 90 in the mirogabalin add-on group and 89 in the NSAIDs alone group were included in the efficacy analysis. The reduction in NRS score for lower limb pain from baseline to Week 8 was significantly greater in the mirogabalin add-on group than in the NSAIDs alone group, with least squares mean changes of - 3.8 [95% confidence interval (CI): - 4.4, - 3.3] and - 2.2 (- 2.8, - 1.7), respectively [intergroup difference - 1.6 (- 2.4, - 0.8); P < 0.001]. EQ-5D-5L and NRS score for sleep disturbance both significantly improved over the study period with mirogabalin add-on treatment compared with NSAIDs alone [intergroup difference: 0.0653 (95% CI 0.0235, 0.1071); P = 0.002 and - 1.3 (- 1.9, - 0.7); P < 0.001, respectively]. No severe or serious TEAEs were observed. In the mirogabalin add-on group, ADRs were observed in 48.9% of participants, with somnolence (31.1%) and dizziness (18.9%) being the most common.

Conclusion: The addition of mirogabalin to NSAIDs treatment significantly improved pain, quality of life, and sleep disturbance in patients with LDH, with no previously undocumented safety concerns identified.

Trial registration: Japan Registry of Clinical Trials (jRCTs061220102, registered 27/February/2023, https://jrct.mhlw.go.jp/en-latest-detail/jRCTs061220102 ).