Dr. Lee next discussed sublingual cyclobenzaprine (TNX-102 SL), which in August 2025 became the first FDA-approved treatment for fibromyalgia since milnacipran in 2009. Oral cyclobenzaprine has often been used off-label by clinicians to treat fibromyalgia, but the sublingual form is felt to have more rapid absorption and potentially improved pharmacokinetics compared to oral formulations. In two pivotal double-blind, placebo-controlled trials, sublingual cyclobenzaprine produced a statistically significant reduction in pain intensity scores versus placebo for patients with fibromyalgia, with 46–47% of patients achieving at least a 30% improvement in pain at 14 weeks.2-3 These improvements are not consistently observed with oral cyclobenzaprine, which has shown only modest effects on sleep and no significant impact on pain or global function in fibromyalgia populations.4
Dr. Lee also discussed medications that are not prescribed exclusively for pain but nevertheless appear to have analgesic effects. Janus kinase (JAK) inhibitors are well known to rheumatologists who manage inflammatory arthritides, but it’s less commonly known that these medications may act directly or indirectly to decrease pain via multiple pathways, such as through the central nervous system (CNS), dorsal root ganglion and peripheral nerves at the joints. In one paper cited by Dr. Lee, the 60% of the effect of the JAK inhibitor baricitinib on pain seemed to occur via “non-inflammatory” pathways.5 Dr. Lee believes the future of pain management in the rheumatic diseases will rest on understanding these non-inflammatory pathways of pain modulation, personalizing pain management for patients (including by phenotyping pain as nociceptic versus nociplastic), using combination therapies (such as with an anti-inflammatory along with a central analgesic), and integrating behavioral interventions.
The session may have been about pain, but the audience left feeling relieved to have gained such newfound knowledge from the speakers. Much remains to be done to help patients who are suffering, but now it appears there is more hope to do so.
Jason Liebowitz, MD, FACR, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.
References
- Bernardy K, Klose P, Busch AJ, et al. Cognitive behavioural therapies for fibromyalgia. Cochrane Database Syst Rev. 2013 Sep 10;2013(9):CD009796.
- Lederman S, Arnold LM, Vaughn B, et al. Efficacy and Safety of Sublingual Cyclobenzaprine for the Treatment of Fibromyalgia: Results From a Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2023 Nov;75(11):2359-2368.
- Lederman S, Arnold LM, Vaughn B, et al. Pain Relief by Targeting Nonrestorative Sleep in Fibromyalgia: A Phase 3 Randomized Trial of Bedtime Sublingual Cyclobenzaprine. Pain Med. 2025 Jul 8:pnaf089.
- Oldfield BJ, Gleeson B, Morford KL, et al. Long-Term Use of Muscle Relaxant Medications for Chronic Pain: A Systematic Review. JAMA Netw Open. 2024 Sep 3;7(9):e2434835.
- Taylor PC, Lee YC, Fleischmann R, et al. Achieving Pain Control in Rheumatoid Arthritis with Baricitinib or Adalimumab Plus Methotrexate: Results from the RA-BEAM Trial. J Clin Med. 2019 Jun 12;8(6):831.
