Sublingual cyclobenzaprine can significantly reduce daily pain for patients with fibromyalgia, according to results of a phase 3 trial published in Arthritis Care & Research.
In the United States, 3 medications are approved for the management of fibromyalgia pain. In a survey of patients with fibromyalgia, 70% reported using prescription pain medications, but only 19% reported being very satisfied with their current treatment.
The RELIEF (ClinicalTrials.gov Identifier: NCT04172831) study was a phase 3, double-blind, multicenter, placebo-controlled trial designed to evaluate the safety and efficacy of sublingual cyclobenzaprine (TNX-102 SL). Patients (N=503) with fibromyalgia and generalized pain symptoms lasting 3 months or longer were randomly assigned in a 1:1 ratio to receive 5.6 mg TNX-102 SL (n=248) or a placebo (n=255) taken at bedtime for 14 weeks.
During the first 2 weeks, the participants were instructed to take a single tablet nightly and thereafter, 2 tablets. Efficacy was evaluated using a daily pain diary and quantified using an 11-point numeric rating scale (NRS) score.
The patients were aged mean 49.6 (SD, 9.8) years, 95.2% were women, 87.1% were White, they had an average BMI of 32.0 (SD, 6.4) kg/m2, they had been diagnosed with fibromyalgia 9.1 (SD, 8.2) years previously, and average diary pain was 6.1 (SD, 1.1).
At week 14, the TNX-102 SL recipients reported a greater decrease in the average weekly pain scores (least squares mean difference [LSMD], -1.91) compared with placebo (LSMD, -1.51; P =.01). Patients who received the sublingual cyclobenzaprine were more likely to report a 30% or greater reduction in daily pain at week 14 compared with placebo (odds ratio [OR], 1.67; 95% CI, 1.16-2.40; P =.006).
The first key secondary endpoint was not met, indicating that TNX-102 SL recipients were not more likely to report a ‘much improved’ or better Patient Global Impression of Change (PGIC) response compared with placebo (OR, 1.44; 95% CI, 0.99-2.10; P =.058).
As the first secondary endpoint did not reach significance, the remaining secondary endpoints were considered nominal. However, there was evidence that TNX-102 SL was favored over placebo for the outcome of the change in Fibromyalgia Impact Questionnaire Revised (FIQR) scores from baseline (P =.007) as well as greater improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance (P <.001) and fatigue (P =.018) scores from baseline.
Most TNX-102 SL recipients (59.7%) and nearly half of placebo recipients (46.3%) reported 1 or more treatment-emergent adverse event, among whom 44.4% and 20.4% of individuals’ events were possibly related to treatment. Overall, 8.9% of the TNX-102 SL and 3.9% of the placebo groups discontinued the study due to adverse events.
In the cohort that received the sublingual cyclobenzaprine, the most common adverse events were oral hypoesthesia (17.3%), oral paresthesia (5.6%), and product taste abnormalities (4.4%).
“[T]reatment with TNX-102 SL was associated with significant reductions in daily pain and was generally safe and well tolerated in patients with fibromyalgia,” the investigators report.
Disclosures: This research was supported by Tonix Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Lederman S, Arnold LM, Vaughn B, Kelley M, Sullivan GM. Efficacy and safety of TNX-102 SL (sublingual cyclobenzaprine) for the treatment of fibromyalgia: results from the randomized, placebo-controlled RELIEF rrial. Arthritis Care Res. Published online May 11, 2023. doi:10.1002/acr.25142