Dataset Information

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. 50.0%, P = 0.0006, and 47.6% vs. 32.4%, P = 0.0523). In the mirogabalin and NSAIDs group, the incidences of TEAEs and adverse drug reactions were 60.9% and 57.3%, respectively, and the most common TEAEs were somnolence (30.0%) and dizziness (25.5%).

Conclusions

The addition of mirogabalin to NSAIDs improved VAS, EQ-5D-5L, and PGIC. The main TEAEs were somnolence and dizziness. The addition of mirogabalin to NSAIDs improved peripheral neuropathic pain associated with LSS and raised no new safety concerns.

Trial registration

Japan Registry of Clinical Trials (jRCTs021200007).

SUBMITTER: Nikaido T

PROVIDER: S-EPMC9298169 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundFor 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.MethodsIn 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.ResultsOf 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.ConclusionsAddition 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 registrationJapan Registry of Clinical Trials jRCTs071200053 (registered 17/11/2020).

Project description:Purpose:To develop a self-administered diagnostic screening questionnaire for lumbar spinal stenosis (LSS) consisting of items with high content validity and to investigate the diagnostic value of the questionnaire and the items. Patients and Methods:A self-reported diagnostic LSS screening questionnaire was developed based on items from the existing literature describing key symptoms of LSS. The screening questionnaire (index test) was to be tested in a cohort of patients with persistent lumbar and/or leg pain recruited from a Danish publicly funded outpatient secondary care spine clinic with clinicians performing the reference test. However, to avoid unnecessary collection of data if the screening questionnaire proved to be of limited value, a case-control design was incorporated into the cohort design including an interim analysis. Additional cases for the case-control study were recruited at two Danish publicly funded spine surgery departments. Prevalence, sensitivity, specificity and diagnostic odds ratio (OR) were calculated for each individual item, and AUC (area under the curve) was calculated to examine the performance of the full questionnaire. Results:A 13-item Danish questionnaire was developed and tested in 153 cases and 230 controls. The interim analysis was not in favour of continuing the cohort study, and therefore, only results from the case-control study are reported. There was a positive association for all items except the presence of back pain. However, the association was only moderate with ORs up to 3.3. When testing the performance of the whole questionnaire, an AUC of 0.72 was reached with a specificity of 20% for a fixed sensitivity of 95%. Conclusion:The items were associated with LSS and therefore have some potential to identify LSS patients. However, the association was not strong enough to provide sufficient accuracy for a diagnostic tool. Additional dimensions of symptoms of LSS need identification to obtain a reliable questionnaire for screening purposes.

Project description:IntroductionCentral neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson's disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI.MethodsThis 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5-10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ).ResultsOf the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were -2.3 ± 21.13 mm (CNePSCI), -17.0 ± 24.99 mm (CPSP), and -17.1 ± 35.32 mm (CNePPD).ConclusionMirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study.Trial registrationClinicalTrials.gov identifier, NCT03901352.

Project description:ObjectiveTo comprehensively compare and assess the effects of different lumbar fusion techniques in patients with lumbar spinal stenosis (LSS).MethodsPubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched up to December 24, 2022 in this network meta-analysis. Outcomes were pain (pain, low back pain, and leg pain), Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), complications, reoperation, and fusion. Network plots illustrated the direct and indirect comparisons of different fusion techniques for the outcomes. League tables showed the comparisons of any two fusion techniques, based on both direct and indirect evidence. The efficacy of each fusion technique for LSS was ranked by rank probabilities.ResultsTotally 29 studies involving 2,379 patients were eligible. For pain, percutaneous endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) was most likely to be the best technique, followed by minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), extreme lateral interbody fusion (XLIF), and transforaminal lumbar interbody fusion (TLIF). Percutaneous endoscopic posterior lumbar interbody fusion (Endo-PLIF) had the greatest likelihood to be the optimal technique for low back pain, followed sequentially by MIS-TLIF, minimally invasive posterior lumbar interbody fusion (MIS-PLIF), XLIF, Endo-TLIF, TLIF, oblique lumbar interbody fusion (OLIF), posterior lumbar interbody fusion (PLIF), and posterolateral lumbar fusion (PLF). MIS-PLIF was ranked the most effective technique concerning leg pain, followed by Endo-TLIF, MIS-TLIF, TLIF, Endo-PLIF, PLIF, OLIF, PLF, and XLIF. As regards JOA scores, Endo-TLIF had the maximum probability to be the best technique, followed by MIS-TLIF and TLIF. Endo-PLIF had the greatest likelihood to be the optimum technique for complications, followed by TLIF, MIS-TLIF, Endo-TLIF, OLIF, and XLIF.ConclusionMinimally invasive fusion techniques may be effective in the treatment of LSS, compared with traditional techniques. Minimally invasive techniques were likely non-inferior with regards to postoperative complications.