Background Autonomic dysfunction has been studied in rheumatic disorders as a significant risk predictor related to sudden cardiac death. There is need to study the effect of different disease modifying anti-rheumatic diseases (DMARDs) (synthetic & biologics) which are routinely employed in the treatment of RA and AS, since there is no published literature in this regard.
Objectives We examined the clinical efficacy of DMARDs on autonomic neuropathy in patients with RA and AS.
Methods We evaluated total 35 patients in which 23 of RA aged between 26-67 years, disease duration 0.6-28 years (16 DMARDs naive and 7 biologics naive) and 12 patients with AS aged between 20-50 years, disease duration 2-18 years (7 DMARDs naive and 5 biologics naïve). 20 aged matched healthy subjects aged between 27-57 years were also enrolled from clinic staff as a control population. Autonomic function was assessed by applying a battery of non invasive cardiovascular reflex tests according to Ewing1 and peripheral sympathetic autonomic function was assessed by Sudoscan2 (Sudoscan-Impeto Medical Device, EZS 01750010193 Paris France). Five cardiovascular reflex tests used in the assessment of cardiovascular autonomic neuropathy (CAN). They are the heart rate (HR) responses to the deep breathing, standing up and Valsalva manoeuvre and the blood pressure (BP) responses to standing up and sustained handgrip. Autonomic dysfunction is considered when two or more of the heart rate tests are abnormal3.
Results Patients with RA and AS had abnormal autonomic function compared with healthy controls. After 12 weeks treatment of RA and AS with combination synthetic DMARDs, HR response to standing in RA patients significantly improved. After treatment of RA and AS with different biologic DMARDs (3 infusions of TNFi/tocilizumab, 2 infusions of rituximab) there was significant improvement in HR responses to the deep breathing (p<0.05), standing up (p<0.05) and Valsalva manoeuvre in RA (p=0.03), sustained handgrip in AS (p=0.02)and sudomotor function (p<0.05) in RA and AS. After 12 weeks treatment of RA and AS with synthetic DMARDs 22.2% (2/9) RA patients improved cardiovascular autonomic neuropathy while there was no improvement in CAN in AS. After treatment with biologic DMARDs, 85% (6/7) RA patients and 100% (2/2) AS patients had significantly improved cardiovascular autonomic neuropathy. 66.6% (2/3) of the biologics naïve RA patients and 100% (2/2) AS patients who had sudomotor dysfunction improved significantly with biologics treatment but there was no significant improvement in sudomotor function in RA and AS patients treated with synthetic DMARDs. RA and AS patients with normal autonomic function had no change in their autonomic function after treatment with synthetic or biologic DMARDs.
Conclusions Synthetic DMARDs significantly improved HR response to standing in RA and sudomotor function in both RA and AS patients. Surprisingly, biologics DMARDs have potential to significantly improve both cardiovascular autonomic neuropathy and sudomotor function in RA and AS patients.
Ewing DJ et al. Clin Endocrinol Metab. 1986; 15:855-888.
Mayaudon H et al. Diabetes Metab. 2010; 36:450–454.
Aydemir M et al. Lupus. 2010; 19:255–61.
Disclosure of Interest None Declared
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