Bedtime sublingual Cyclobenzaprine may improve pain, fatigue and sleep in Fibromyalgia, finds a new study. New data was presented by investigators at the American College of Rheumatology (ACR) 2021 Convergence.
Fibromyalgia (FM) is characterized by fatigue and altered sleep, memory and mood. TNX-102 SL* Cyclobenzaprine HCl sublingual tablets, 'TNX' is known to target improvement in sleep quality in order to ease pain. Previous studies of TNX at a 2.8 mg dose in Fibromyalgia showed signals for broad efficacy but narrowly missed significance on primary outcome of daily diary pain reduction.
In a phase 3 trial "RELIEF", Gregory Sullivan and team revealed that TNX at the 5.6 mg dose when given at bedtime significantly reduced daily pain, provided a larger rate of ≥30% pain responders. It showed improving activities in sleep, fatigue, and other Fibromyalgia symptoms and measures of function.
The findings of the trial are published in The American College of Rheumatology.
The objective of the trial was to evaluate Phase 3 trial ('RELIEF') efficacy and safety of TNX for FM at twice the dose, 5.6 mg.
The trial included sample of 503 patients meeting 2016 FM diagnostic criteria and were enrolled from 39 U.S. sites and received TNX 2.8 mg or placebo for 2 weeks followed by TNX 5.6 mg or placebo for 12 weeks. Primary outcome measure was change from baseline in weekly average of daily diary pain scores (0-10 NRS) at Week 14, analyzed by mixed model repeated measures with multiple imputation (MMRM-MI). The 1st key secondary analysis was Patient Global Impression of Change (PGIC) responders by logistic regression. Remaining key secondaries (by MMRM-MI) included: Fibromyalgia Impact Questionnaire-Revised (FIQ-R) symptom domain; FIQ-R function domain; Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance; PROMIS Fatigue; and daily diary NRS of sleep quality.
The results of the trial were
• TNX was effective in decreasing daily diary pain compared to placebo (p=0.010). A ≥30% pain reduction responder analysis indicated 46.8% TNX responders vs. 34.9% on placebo (p=0.006). By PGIC, 37.5% on TNX were responders, which was numerically but not significantly greater than 29.4% on placebo (p=0.058).
• TNX also provided greater separation from placebo on: FIQ-R Symptoms (p=0.007), Function (p=0.009); PROMIS Sleep Disturbance (p< 0.001) and Fatigue (p=0.018); and daily diary sleep quality (p< 0.001).
• In the TNX group, 82.3% completed vs. 83.5% on placebo. Systemic adverse events (AEs) were infrequent, with somnolence/sedation the only category at a rate of ≥ 5% on TNX (5.6% TNX; 1.2% placebo).
• The most common local administration site reaction was oral numbness (17.3% TNX; 0.8% placebo) which was episodic and typically temporally related to dosing, resolved in < 60 min.
Sullivan and team concluded that "Bedtime TNX at the 5.6 mg dose significantly reduced daily pain, provided a larger rate of ≥30% pain responders. It showed activity in improving sleep, fatigue, and other FM symptoms and measures of function. In addition, nightly TNX 5.6 mg was well tolerated."
reference:
Sullivan G, Kelley M, Iserson A, Peters P, Peters A, Flint C, Gendreau J, Harris H, Vaughn B, Lederman S. TNX-102 SL (Sublingual Cyclobenzaprine) for the Treatment of Fibromyalgia in the RELIEF Study: Positive Results of a Phase 3 Randomized, Double-Blind, Placebo-Controlled Multicenter Efficacy and Safety Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10).
https://acrabstracts.org/abstract/tnx-102-sl-sublingual-cyclobenzaprine-for-the-treatment-of-fibromyalgia-in-the-relief-study-positive-results-of-a-phase-3-randomized-double-blind-placebo-controlled-multicenter-efficacy-and-safet/.
Accessed November 7, 2021.