Effects of Pharmacotherapy on Fibromyalgia Symptoms and Functional Outcomes in Systemic Lupus Erythematosus: A Moderation Analysis on a Multicenter Canadian Study

Objectives Fibromyalgia (FM) symptoms are a common comorbidity in systemic lupus erythematosus (SLE), contributing to increased pain, fatigue, and insomnia. These symptoms can significantly impair physical and cognitive function, making it harder to perform daily activities, exercise, and tasks requiring concentration. This study examines the effect of FM symptoms on function and explores how various treatment approaches can moderate these effects through a multicenter cross-sectional analysis of SLE patients from 7 Canadian clinics. Methods Data on disease burden metrics (FM symptoms, pain areas, disease activity, and irreversible damage), medication use (antimalarials, corticosteroids, immunosuppressants, biologics and narcotics), and sociodemographic factors were collected. Linear mixed-effects models evaluated the effect of FM symptoms and other disease burden variables on 5 functional outcomes: fatigue severity (FSS), cognitive dysfunction (PDQ), disability (WHODAS), depression (BDI), and work role functioning (WRF). Moderation models were used to assess if SLE treatments ameliorated the effect of these variables on function, while correcting for multiple testing. Results The models established that a higher number of reported fibromyalgia symptoms was the strongest predictor of functional impairment, being significantly associated with increased fatigue (β = 1.06, p < 0.001), cognitive dysfunction (β = 1.21, p < 0.001), and higher disability (β = 0.68, p < 0.001), and depression scores (β = 0.73, p < 0.001). Conversely, irreversible damage scores were uniquely linked to worsened work role functioning (β = −4.41, p = 0.020). Building on these models, moderation analyses revealed that certain treatments lowered the effect of the disease burden metrics on various function metrics (Figure 1). Immunosuppressants moderated the impact of organ damage on disability from β = 2.62 to β = 0.45 (p = 0.022) and perceived deficits from 2.28 to −0.84 (p = 0.041). Corticosteroids attenuated the association between FM symptoms and cognitive dysfunction falling from β = 1.42 to β = 0.14 in users (p = .024). Figure 1. Simple Slopes of Effects of Immunosuppressants and Corticosteroids Conclusion This study demonstrates that the reported number of fibromyalgia symptoms is the dominant factor driving functional burden across nearly all measured domains in SLE, surpassing the impact of disease activity. Most significantly, we provide evidence that certain SLE treatments act as functional shields: corticosteroids protecting cognition from FM effects and immunosuppressants mitigating disability linked to damage. These moderation effects strongly support tailoring treatment not only to disease activity but also to the patient’s functional risk profile, moving clinical practice closer to truly personalized medicine. Supported by a CIORA grant