Sublingual Cyclobenzaprine Significantly Reduces Fibromyalgia Pain

Sublingual cyclobenzaprine may provide a new pain relief option for patients with daily fibromyalgia pain.

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 ( 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.

[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 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.

This article originally appeared on Clinical Pain Advisor


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