Giulio Giancaspro, M.D., Cinzia Rotondo, M.D., Raffaele Barile, M.D., Valeria Rella, M.D., Jlenia Casciaro, M.D., Luigi Nardella, M.D., Francesco Paolo Cantatore, M.D., Addolorata Corrado, M.D.. J Rheum Dis -0001;0:232-. https://doi.org/10.4078/jrd.2025.0136

Background: Fibromyalgia syndrome (FS) is one of the most common causes of chronic generalised pain and often complicates the therapeutic management of inflammatory chronic arthritis (ICA), negatively impacting both the real assessment of disease activity and the perception of response. Our study aims to evaluate in a group of patients with ICA, multi-resistant to biologic/target synthetic disease-modifying antirheumatic drugs (b/ts-DMARDs), both the impact of FS on the possibility of achieving low disease activity (LDA) or remission (REM) and the possible improvement in the severity of FS symptoms, after starting b/ts-DMARDs with different a mechanism of action (MoA). Methods: A prospective study was conducted, from January 2023 to December 2024, on patients who fulfil the classification criteria for psoriatic arthritis (PsA) or fulfil the 2010 American College of Rheumatology criteria for RA. Results: Sixty-four Caucasian patients with ICA, of which 47 with FS, were enrolled in the study. At the baseline visit, FS patients had a significantly shorter ICA disease duration, worse fibromyalgia symptom-related indices (such as Fibromyalgia Severity Scale (FSS), Widespread Pain Index (WPI), and Symptom Severity Scale (SSS)) and functional and disability scores (such as health assessment questionnaire (HAQ) and Functional Assessment of Chronic Illness Therapy (FACIT)), and a higher basal value of Disease Activity in Psoriatic Arthritis (DAPSA) score compared to patients without FS. After 6 months of starting b/ts-DMARDs, no differences in severity of arthritis clinimetric indices (disease activity score (DAS) 28 (erythrocyte sedimentation (ESR)) and DAPSA) and Visual Analogue Scale (VAS) pain were found between the patients with FS compared to those without. At the follow-up visit, 36% of the whole group of patients were in LDA (36% ICA patients with FS vs. 35% of ICA patients without FS; p = 0.080), while 17% of patients reached REM (11% ICA with FS vs. 35% ICA without FS patients; p = 0.031). The FS presence appeared to be a factor associated with failure to reach REM (OR 4.5 (95%CI: 1.1–17.8), p = 0.028), but not for achieving LDA (OR 2.7 (95%CI: 0.8–8.9), p = 0.099). The overall retention rate at 6 months was 79%; in particular, 11 patients discontinued treatment with b/ts-DMARD, 69% of whom belonged to the FS group (p = 0.489). Among the group of patients with ICA and FS, patients in LDA/REM presented an important improvement in FSS, SSS, and VAS pain, with the best percentage variation from the baseline of these indices compared to patients who did not achieve the LDA/REM. Of note, sixteen patients with FS at the baseline no longer met the diagnostic criteria for FS after 6 months of follow-up. Conclusions: The presence of FS seems to negatively impact the achievement of REM, but not LDA, in both RA and PsA patients, even in b/ts-DMARDs patients with multi-failure of at least two different MOAs. Only a cluster of patients with FS, presumably those with FS triggered and/or amplified by the chronic joint inflammatory process, appear to improve their perception of FS severity by achieving ICA LDA/REM. However, these findings require further supporting data for more accurate validation.