Disease-modifying anti-rheumatic drugs improve autonomic neuropathy in arthritis: DIANA study

Abstract

Autonomic neuropathy (AN) is a risk predictor for sudden cardiac death in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, the impact of most commonly employed disease-modifying anti-rheumatic drug (DMARD) therapy on autonomic neuropathy in rheumatic diseases is not known. Hence, we investigated the efficacy of DMARDs on autonomic neuropathy in RA and AS. We performed autonomic function assessment in 60 patients in this open-label, 12-week pilot study including 42 patients with RA, 18 with AS, and 30 aged-matched healthy subjects. The methodology included assessment of cardiovascular autonomic reflex tests according to Ewing. Parasympathetic dysfunction was established by performing three tests: heart rate response to deep breathing, standing, and Valsalva tests. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing and handgrip tests. Sudomotor function was assessed by Sudoscan. Cardiovascular reflex tests were impaired significantly among the patients as compared to healthy subjects (p < 0.05). Autonomic neuropathy was more pronounced in biologic-naive RA and AS patients. After treatment with combination synthetic DMARDs, parasympathetic, and sudomotor dysfunction significantly (p < 0.05) improved in RA and AS. Biologic DMARDs significantly improved parasympathetic, sympathetic and peripheral sympathetic autonomic neuropathy (p < 0.05) in biologic-naive RA and AS patients. In conclusion, synthetic DMARDs improved parasympathetic and sudomotor dysfunction in both DMARD-naive RA and AS patients. However, biologic DMARDs improved parasympathetic, sympathetic and sudomotor dysfunction to a greater extent than synthetic DMARDs in both RA and AS patients.

Fatigue in chronic liver disease: New insights and therapeutic approaches

“…Similar observations have been made in patients with chronic nonhepatic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease . Moreover, elevated systemic TNFα levels have also been linked to the development of autonomic nervous system dysfunction in animal models and in patients . These observations potentially implicate TNFα as an important link between chronic liver injury, sickness behaviours (including fatigue) and autonomic dysfunction.…”

Inflammation and cardiovascular autonomic dysfunction in rheumatoid arthritis: a bidirectional pathway leading to cardiovascular disease

“…Similarly, there is also evidence indicating the benefits of disease‐modifying anti‐rheumatic drugs in inflammatory and autonomic profiles of RA patients (Syngle et al . ). However, whilst most of these findings do not associate the observed improvements with cardiovascular disease outcomes, other studies have demonstrated the beneficial impact of such interventions on cardiovascular risk markers, reinforcing the importance of the role of the autonomic nervous system as a potential pathway for improvement.…”

“…Recently, the cholinergic anti‐inflammatory pathway has been investigated as a therapeutic alternative to several diseases, including RA (Syngle et al . ; Koopman et al . ).…”

“…Recently, the cholinergic anti-inflammatory pathway has been investigated as a therapeutic alternative to several diseases, including RA (Syngle et al 2015;Koopman et al 2016). Accordingly, it has been elegantly demonstrated that stimulation of vagal nerves using a surgically implantable neuromodulation device inhibits TNF production and reduces disease activity in patients with RA for up to 84 days (Koopman et al 2016).…”

Tumor necrosis factor-alpha blockade with etanercept improves autonomic dysfunction in rheumatoid arthritis

“…Therapeutic effect of diseasemodifying anti-rheumatic drugs (DMARDs) and biologic DMARDs (infliximab, tociluzimab, rituximab) on autonomic neuropathy has been demonstrated in RA and ankylosing spondylitis (AS) patients. [3][4][5] However, there is no specific treatment recommendation for autonomic neuropathy in RA. Treatment with TNF-inhibitor (TNFi) etanercept has revolutionized the treatment of RA, however, its impact on autonomic neuropathy has not been reported.…”