INTRODUCTION: The present analysis was a post hoc analysis of the MiroTAS study, a 12-week, randomized, open-label, parallel-group study conducted at 32 centers in Japan (jRCTs021200007)1. In the MiroTAS study, lumbar spinal stenosis (LSS) patients with leg pain were randomized in a 1:1 ratio to treatment with NSAIDs plus mirogabalin (MGB add-on group) or treatment with NSAIDs alone (NSAIDs alone group), and the MGB add-on group showed significantly improved leg pain compared with the NSAIDs alone group. In this post-hoc analysis of the MiroTAS, we examined the timing of onset of adverse drug reaction (ADR) caused by MGB, factors influencing the onset of the ADR, patient background influencing the improvement of leg pain with MGB, and the relationship between baseline leg numbness and the improvement of quality of life with MGB.
METHODS: Safety outcomes were 1) the timing of the first onset of MGB-related ADRs, such as somnolence, dizziness, peripheral edema, and edema in the MGB add-on group, and 2) the relationships between the occurrence of ADRs and patient characteristics, or MGB efficacy at Week 12 (Patient Global Impression of Change [PGIC] score, change in EQ-5D-5L score). Efficacy outcomes were relationships of the degree of improvement in leg pain (by visual analog scale [VAS] score) with patient characteristics; relationships of baseline numbness severity (by Spine painDETECT questionnaire [SPDQ] score) with the improvement in EQ-5D-5L score. Statistical analyses were performed using t-test and Spearman's rank correlation coefficient.
RESULTS: Among the 110 patients in the MGB add-on group, patient characteristics did not affect the incidence of ADRs. The first onset of ADRs mainly occurred after the first administration of MGB and the titration period. Patients with the ADRs showed a significant improvement in EQ-5D-5L scores from baseline to Week 12 compared with those without (difference: 0.0767; p = 0.0304 by t-test). The proportion of patients with a PGIC score ≤3 at Week 12 was tended to be numerically higher in patients with ADRs vs those without. Except in cases with complications such as spondylolysis/spondylolisthesis, there were no differences in the proportion of patients with reduced leg pain by the VAS score (improvement ≥20 mm) at Week 12 based on patient characteristics. Baseline SPDQ numbness score was positively correlated with improvement in EQ-5D-5L score at Week 12 (Spearman’s rank correlation coefficient r = 0.2811, p = 0.0092).
DISCUSSION: Administration of MGB to NSAIDs in LSS patients improved leg pain regardless of patient characteristics, and it is expected to have a greater effect on improving patient quality of life (QOL) in those with higher baseline numbness scores. Meanwhile, the occurrence of MGB-related ADRs was associated with the efficacy indicators of MGB, such as PGIC and EQ-5D-5L scores. With paying attention to the timing of the initial ADRs identified in this study, it is necessary to continuously monitor both the effectiveness of MGB and the onset of ADRs.