Efficacy and safety of add-on mirogabalin to conventional therapy for the treatment of peripheral neuropathic pain after thoracic surgery: the multicenter, randomized, open-label ADMIT-NeP study
Authors: Miyazaki Takuro , Matsumoto Keitaro , Sato Toshihiko , Sano Isao , Furukawa Katsuro , Shimoyama Koichiro , Kamohara Ryotaro , Suzuki Makoto , Kondou Masamichi , Ikeda Norihiko , Tabata Shunsuke , Shiosakai Kazuhito , Nagayasu Takeshi ,   on behalf of the ADMIT-NeP Study group, Doi Ryoichiro , Waseda Ryuichi , Nakamura Akihiro , Akao Keiko , Hatachi Go , Tagawa Tsutomu , Imai Makoto , Ikeda Koei , Hagiwara Masaru 
Published: January 2024

Abstract
Background
For chronic pain after thoracic surgery, optimal timing of its diagnosis and effective treatment remains unresolved, although several treatment options are currently available. We examined the efficacy and safety of mirogabalin, in combination with conventional pain therapy (nonsteroidal anti-inflammatory drugs and/or acetaminophen), for treating peripheral neuropathic pain (NeP) after thoracic surgery.

Methods
In this multicenter, randomized, open-label, parallel-group study, patients with peripheral NeP were randomly assigned 1:1 to mirogabalin as add-on to conventional therapy or conventional treatment alone.

Results
Of 131 patients of consent obtained, 128 were randomized (mirogabalin add-on group, 63 patients; conventional treatment group, 65 patients). The least squares mean changes (95% confidence interval [CI]) in Visual Analogue Scale (VAS) score for pain intensity at rest from baseline to Week 8 (primary endpoint) were − 51.3 (− 54.9, − 47.7) mm in the mirogabalin add-on group and − 47.7 (− 51.2, − 44.2) mm in the conventional group (between-group difference: − 3.6 [95% CI: − 8.7, 1.5], P = 0.161). However, in patients with Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score (used for the screening of NeP) ≥ 12 at baseline, the greater the S-LANSS score at baseline, the greater the decrease in VAS score in the mirogabalin add-on group, while no such trend was observed in the conventional treatment group (post hoc analysis). This between-group difference in trends was statistically significant (interaction P value = 0.014). Chronic pain was recorded in 7.9% vs. 16.9% of patients (P = 0.171) at Week 12 in the mirogabalin add-on vs. conventional treatment groups, respectively. Regarding activities of daily living (ADL) and quality of life (QOL), changes in Pain Disability Assessment Scale score and the EQ-5D-5L index value from baseline to Week 8 showed significant improvement in the mirogabalin add-on group vs. conventional treatment group (P < 0.001). The most common adverse events (AEs) in the mirogabalin add-on group were dizziness (12.7%), somnolence (7.9%), and urticaria (3.2%). Most AEs were mild or moderate in severity.

Conclusions
Addition of mirogabalin to conventional therapy did not result in significant improvement in pain intensity based on VAS scores, but did result in significant improvement in ADL and QOL in patients with peripheral NeP after thoracic surgery.

Trial registration
Japan Registry of Clinical Trials jRCTs071200053 (registered 17/11/2020).