Background/Purpose: Chronic inflammation in rheumatoid arthritis (RA) is associated with an increased cardiovascular risk, possibly due to disrupted vascular vasodilation. Within 12 weeks adalimumab and etanercept normalize vascular dysfunction. We here analyze whether stopping adalimumab or etanercept is associated with worsening of vasodilator function using the forearm vascular model using intraarterial AcetylCholine (ACh) and Sodium NitroPrusside (SNP) measuring forearm vasodilator function with plethysmography.

Methods: 35 patients participating in the nationwide tumor necrosis factor inhibitor stop study were assessed for eligibility and provided informed consent for this add-on study (exclusion criteria: uncontrolled hypertension); 8 were randomly allocated to the continuation arm of adalimumab/etanercept, 27 to the intervention arm of stopping the adalimumab or etanercept. Lost in follow up were 2 and 5 patients respectively. In the stopped group 8 flared and 14 did not flare. Forearm Vasodilation was assessed twice: before cessation of the intervention (visit 1) and 6 months afterwards (visit 2) or earlier when flaring occurred; flare defined as DAS28>3.2 plus increase exceeding 0.6 compared with baseline.

Results: In patients who stopped but did not flare (group B) vasodilator response to SNP and ACh did not differ between visit 1 and 2. In patients who flared after stopped adalimumab or etanercept (group C) vasodilator responses to ACh and SNP were significantly reduced during visit 2 when compared with visit 1, see table. In patients from group A who continued adalimumab/etancercept no flares were observed and vasodilator responses did not significantly differ between both visits. Table: percentage change in forearm blood flow (FBF) in infused versus non-infused arm in group C (n=8) vs group B (n=14); means (SE)

* P<0.05 for comparison visit 1 to visit 2 (repeated measures ANOVA with vasodilator dose and visit as within subject factors)

Conclusion: Forearm vasodilator function is reduced after interruption of adalimumab or etanercept but only when rheumatoid arthritis reactivates. This indicates that without close rheumatological monitoring after interrupted biological treatment, ie stopped TNF inhibitor therapy, microvascular functional impairment will occur in those who flare, with potentially devastating implications for cardiovascular health. Funding for this study was gratefully acknowledged from Abbvie (unrestricted grant)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impaired-vasodilator-function-in-rheumatoid-arthritis-patients-who-flared-due-to-stopping-adalimumab-or-etanercept/