New Treatment for Fibromyalgia? Will It Help or Harm? Save

For years, the pharmacologic treatment landscape for fibromyalgia has remained relatively unchanged, with limited therapeutic options despite a substantial disease burden. This condition is characterized by chronic widespread pain, fatigue, sleep disturbance and functional impairment. In August 2025, cyclobenzaprine HCl sublingual tablets (brand name Tonmya®) became the first newly approved therapy for adults with fibromyalgia in over 15 years. 

At ACR Convergence 2026, abstract 2547 revealed pooled data from the two pivotal 14-week, randomized, placebo-controlled phase 3 clinical trials, RELIEF and RESILIENT. The studies evaluated the efficacy, safety and tolerability of sublingual cyclobenzaprine 5.6 mg versus placebo in 479 cyclobenzaprine patients and 481 patients on placebo. All patients were treated for a diagnosis of primary fibromyalgia, meeting the 2016 revised American College of Rheumatology Fibromyalgia Diagnostic Criteria. This poster presents trial data as number needed to treat (NNT), number needed to harm (NNH) and likelihood to be helped or harmed (LHH). These quantifiable measurements provide easily understood data for patients on the potential benefits and harms of treatment. The NNT, calculated as the inverse of absolute risk reduction, was based on a ≥30% reduction in pain from baseline to the 14 week end of trial. This represents the number of patients needed to receive the treatment rather than placebo for one additional patient to achieve the pain reduction outcome. NNH was calculated as medication discontinuation due to adverse events. The ratio LHH (≥30% pain reduction/discontinuation due to AE) provides comparison of benefit to harm ratio by calculating how many patients report pain reduction for every medication discontinuation.

The study found a number needed to treat of 7 patients (95% confidence interval: 5-12), indicating that seven patients would need to be treated with sublingual cyclobenzaprine rather than placebo for one additional patient to obtain at least a 30% pain reduction. The number needed to harm was 26 (confidence interval 14-110). Discontinuation at 14 weeks included oral adverse events, dry mouth and somnolence. The likelihood to be helped or harmed was calculated at 3.7 suggests that patients were approximately 3.7 times more likely to achieve the pain response than to discontinue treatment because of an adverse event.

These findings provide an encouraging perspective on sublingual cyclobenzaprine as an additional pharmacologic option for fibromyalgia. However, these results should be interpreted in the context of a relatively short 14-week trial duration. Furthermore, adverse events that do not result in treatment discontinuation are not captured by the NNH in this study. Additionally, the clinical endpoint of 30% reduction in pain is a meaningful response, but not necessarily adequate to be the complete therapeutic plan for this disease. As with other pharmacologic treatments for fibromyalgia, sublingual cyclobenzaprine should be considered part of a multimodal treatment approach. Nonpharmacologic interventions, including mind-body therapies, speech optimization, and regular exercise and stretching routines, remain essential components of comprehensive fibromyalgia care.

The study shows that sublingual cyclobenzaprine can be a useful therapy in the arsenal of fibromyalgia and this data led to its FDA-approval. This therapy can be part of the treatment algorithm, though it is important to note that successful patients only achieve partial pain response and the non-pharmacologic interventions including mind-body therapy, optimization of sleep, and regular exercise/stretching routines are the most important aspects in fibromyalgia care.