TY - JOUR
T1 - Vasodilator function worsens after cessation of tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis only if a flare occurs
AU - Rongen, Gerard A.
AU - van Ingen, Iris
AU - Kok, Marc
AU - Vonkeman, Harald
AU - Janssen, Matthijs
AU - Jansen, Tim L.
N1 - Funding Information:
Funding information Funding for this vascular substudy of the POEET trial by Abbvie is gratefully acknowledged. The POEET trial was funded by The Netherlands Organisation for Health Research and Development (ZonMw) and the Government of The Netherlands, Ministry of Health, Welfare, and Sport.
Publisher Copyright:
© 2018, International League of Associations for Rheumatology (ILAR).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Vasodilator function is reported to be reduced in rheumatoid arthritis (RA), and is considered an early sign of vascular dysfunction, which is normalised by TNF inhibitors (TNFi). To optimise cost-effectiveness, tapering or interruption of TNFi therapy in established RA patients is advocated. We explored whether cessation of TNFi results in impaired vasodilator function and whether this relates to the development of a Disease Activity Score (DAS28)-based flare. Forty-one patients were assessed for eligibility as RA with at least 12 months of low disease activity (based on 28 joint counts); 35 enrolled into the randomised study: 8 were randomised to continue, 27 to stopping TNFi. Forearm vasodilation to acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed before cessation of TNFi therapy (visit 1) and 6 months after (dis)continuation of TNFi or at flare (based on DAS28) whichever came first (visit 2). None of the patients who continued their TNFi therapy flared. Eight out of 22 patients who stopped TNFi therapy flared. The vasodilator response to ACh and SNP was reduced significantly in patients who experienced a flare of RA: In patients who did not experience a flare, the vasodilator response to ACh or SNP was not significantly affected. Vasodilator function is reduced after cessation of TNFi, but only when RA reactivates, indicating that early vasodilator dysfunction is a consequence rather than a cause of systemic inflammation in RA and not specifically related to inhibition of TNFα signalling. Without close monitoring, microvascular damage can occur after TNFi interruption with potential devastating implications for cardiovascular health. Trial registration: NCT02130076.
AB - Vasodilator function is reported to be reduced in rheumatoid arthritis (RA), and is considered an early sign of vascular dysfunction, which is normalised by TNF inhibitors (TNFi). To optimise cost-effectiveness, tapering or interruption of TNFi therapy in established RA patients is advocated. We explored whether cessation of TNFi results in impaired vasodilator function and whether this relates to the development of a Disease Activity Score (DAS28)-based flare. Forty-one patients were assessed for eligibility as RA with at least 12 months of low disease activity (based on 28 joint counts); 35 enrolled into the randomised study: 8 were randomised to continue, 27 to stopping TNFi. Forearm vasodilation to acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed before cessation of TNFi therapy (visit 1) and 6 months after (dis)continuation of TNFi or at flare (based on DAS28) whichever came first (visit 2). None of the patients who continued their TNFi therapy flared. Eight out of 22 patients who stopped TNFi therapy flared. The vasodilator response to ACh and SNP was reduced significantly in patients who experienced a flare of RA: In patients who did not experience a flare, the vasodilator response to ACh or SNP was not significantly affected. Vasodilator function is reduced after cessation of TNFi, but only when RA reactivates, indicating that early vasodilator dysfunction is a consequence rather than a cause of systemic inflammation in RA and not specifically related to inhibition of TNFα signalling. Without close monitoring, microvascular damage can occur after TNFi interruption with potential devastating implications for cardiovascular health. Trial registration: NCT02130076.
KW - UT-Hybrid-D
KW - Flow mediated vasodilation
KW - Rheumatoid arthritis
KW - Stopping TNF inhibitor
KW - TNF inhibitors
KW - Vascular smooth cells
KW - Vasodilator function
KW - Endothelial vasodilation
UR - http://www.scopus.com/inward/record.url?scp=85040066954&partnerID=8YFLogxK
U2 - 10.1007/s10067-017-3961-6
DO - 10.1007/s10067-017-3961-6
M3 - Article
C2 - 29307093
AN - SCOPUS:85040066954
SN - 0770-3198
VL - 37
SP - 909
EP - 916
JO - Clinical rheumatology
JF - Clinical rheumatology
IS - 4
ER -