Efficacy and Safety of Add-on Mirogabalin to NSAIDs in Lumbar Spinal Stenosis with Peripheral Neuropathic Pain: A Randomized, Open-Label Study

Abstract

Introduction In Japan, conservative therapy for patients with lumbar spinal stenosis (LSS) includes non-steroidal anti-inflammatory drugs (NSAIDs), prostaglandin E1, tramadol, physical/exercise therapy, and nerve blocks. Mirogabalin, a selective oral α2δ ligand, is approved for treating peripheral neuropathic pain, though data regarding visual analog scores (VAS) for pain in patients with LSS are limited. We investigated the efficacy and safety of mirogabalin as an add-on treatment in patients with LSS taking NSAIDs compared with patients taking NSAIDs only. Methods This multicenter, randomized, open-label study (MiroTAS) was conducted at 32 centers in Japan between June 2020 and October 2021. Patients were randomly assigned to mirogabalin and NSAIDs or NSAIDs alone in a 1:1 ratio. NSAIDs were administered according to their Japanese package inserts; mirogabalin was administered based on renal function [creatinine clearance (CrCL) ≥ 60 mL/min, 5 mg twice daily (BID) in Weeks 1–2, 10 mg BID in Weeks 3–4, and 15 or 10 mg BID after Week 5; CrCL 30 to < 60 mL/min, 2.5 mg BID Weeks 1–2, 5 mg BID Weeks 3–4, and 7.5 or 5 mg BID after Week 5]. The primary endpoint was the change in VAS score for leg pain from baseline to Week 12. Secondary endpoints were quality of life, evaluated using the EuroQol five-dimensional descriptive system (EQ-5D-5L) (at baseline and Week 12) and Patient Global Impression of Change (PGIC) (at Week 12), and safety. Change in VAS score at Week 12 was calculated using a linear mixed model for repeated measures. The safety endpoints were treatment-emergent adverse events (TEAEs) and adverse drug reactions. Results In total, 220 patients who met the eligibility criteria were enrolled. In the mirogabalin and NSAIDs and NSAIDs groups, mean ages (67.8 vs. 70.9 years), proportions of female patients (54.5% vs. 49.0%), mean body weights (63.9 vs. 62.0 kg), mean CrCL values (81.5 vs. 70.7 mL/min), proportions of patients with CrCL 30 to < 60 mL/min (27.3% vs. 33.7%), mean VAS scores (63.8 vs. 62.8 mm), and proportions of patients with VAS score ≥ 60 (53.6% vs. 52.9%) at enrollment were similar. The median durations of LSS were 9.0 and 11.0 months and the spine pain DETECT questionnaire (SPDQ) scores were 6.8 and 7.8, respectively. The least square (LS) mean change in VAS score from baseline to Week 12 was − 24.1 mm in the mirogabalin and NSAIDs group and − 14.2 mm in the NSAIDs group (both P < 0.0001 vs. baseline). The difference in LS mean was − 9.9 [95% confidence interval (CI), − 18.0, − 1.8] ( P = 0.0174). The improvement in EQ-5D-5L score at Week 12 was significantly greater in the mirogabalin and NSAIDs group versus the NSAIDs group [mean difference, 0.0529 (95% CI, 0.0036, 0.1022), P = 0.0357]. At Week 12, the proportions of patients with PGIC scores ≤ 3 and ≤ 2 were higher in the mirogabalin and NSAIDs group vs. the NSAIDs group (76.2% vs. 5...

Impact of Lumbar Surgery on Pharmacological Treatment for Patients with Lumbar Spinal Canal Stenosis: A Single-Center Retrospective Study

“…NSAIDs are also considered one of the potentially inappropriate medications that can cause ADEs, especially for the elderly [ 19 , 20 , 21 ], so careful attention should be paid to the prescription of NSAIDs for LSCS patients, whether before or after lumbar surgery. Pregabalin/mirogabalin has been also reported to have a relatively high incidence of ADEs in patients with LSCS [ 22 , 23 ]. Common ADEs associated with pregabalin and mirogabalin are somnolence, dizziness, peripheral edema, and weight gain [ 22 , 23 ].…”

“…Pregabalin/mirogabalin has been also reported to have a relatively high incidence of ADEs in patients with LSCS [ 22 , 23 ]. Common ADEs associated with pregabalin and mirogabalin are somnolence, dizziness, peripheral edema, and weight gain [ 22 , 23 ]. Especially in elderly patients with LSCS, physicians need to be aware of somnolence and dizziness caused by pregabalin/mirogabalin in terms of increased risk of falls.…”

Inhalation of Pelargonium graveolens Essential Oil Alleviates Pain and Related Anxiety and Stress in Patients with Lumbar Spinal Stenosis and Moderate to Severe Pain

“…Although this pain is frequently treated with gabapentinoids, such as pregabalin and gabapentin [ 38 ], there is insufficient evidence regarding their efficacy and safety in relation to central nervous system inhibition [ 39 ]. The relationship between neuropathic pain and COX-2 has been evaluated in an LPS-induced neuropathic animal model [ 40 ], and a recent randomized controlled trial reported that NSAIDs can improve peripheral neuropathic pain in LSS patients [ 41 ]. Therefore, GEO may act as a long-term modulator of neuropathic pain in patients with LSS, offering potential advantages over NSAIDs, which are recommended only for short-term use.…”

Combined Efficacy of Systemically Acting Diclofenac Sodium Patch and Alpha-2-Delta Calcium Channel Ligand in Chronic Low Back Pain: Subanalysis of a Phase III Study

“…It is conceivable that in this patient group, the combination with diclofenac sodium, which suppresses nociceptive pain, may have resulted in additional pain improvement compared with the non-combination group (placebo group), resulting in a greater change in pain VAS scores. Furthermore, one study reported that the addition of the α2δ Ca 2+ channel ligand mirogabalin in patients treated with NSAIDs for lumbar spinal canal stenosis with peripheral neuropathic pain significantly improved the change in pain VAS scores compared with patients treated with NSAIDs alone [ 14 ], and another found that the combination of celecoxib and pregabalin was more effective than monotherapy [ 10 ]. Although these reports do not directly support an additive effect of the DF systemic patch itself with α2δ Ca 2+ channel ligands, the positive effects of the concomitant use of NSAIDs and α2δ Ca 2+ channel ligands indicate that the DF systemic patch may also be highly likely to have an additive effect in controlling chronic pain, such as that associated with the mixed pain of chronic low back pain.…”