Patterns of Anti-Inflammatory and Immunomodulating Drug Usage and Microvascular Endothelial Function in Rheumatoid Arthritis

Arduino A Mangoni; Richard J Woodman; Matteo Piga; Alberto Cauli; Anna Laura Fedele; Elisa Gremese; Gian Luca Erre; EDRA Study Group

doi:10.3389/fcvm.2021.681327

Patterns of Anti-Inflammatory and Immunomodulating Drug Usage and Microvascular Endothelial Function in Rheumatoid Arthritis

Front Cardiovasc Med. 2021 Jul 19:8:681327. doi: 10.3389/fcvm.2021.681327. eCollection 2021.

Authors

Arduino A Mangoni¹, Richard J Woodman², Matteo Piga^{3

4}, Alberto Cauli^{3

4}, Anna Laura Fedele⁵, Elisa Gremese⁵, Gian Luca Erre^{6

7}; EDRA Study Group

Collaborators

EDRA Study Group:
Floriana Castagna, Marco Piras, Maria Luisa Cadoni, Loredana Taras, Ignazio Cangemi, Martina Dessì, Ilaria Platè, Elisabetta Chessa, Mattia Congia, Alberto Floris, Maria Giovanna Longu, Giuseppe Passiu, Dario Bruno, Gianfranco Ferraccioli

Affiliations

¹ Discipline of Clinical Pharmacology, Flinders Medical Centre, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
² Centre of Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
³ Dipartimento di Scienze Mediche e Sanità Pubblica, Università degli Studi di Cagliari, Cagliari, Italy.
⁴ Unità Operativa Complessa (UOC) di Reumatologia, Policlinico Universitario Azienda Ospedaliero-Universitaria (AOU) Cagliari, Cagliari, Italy.
⁵ Fondazione Policlinico Gemelli-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Università Cattolica del Sacro Cuore, Rome, Italy.
⁶ Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, Università degli Studi di Sassari, Sassari, Italy.
⁷ Dipartimento di Specialità Mediche, Unità Operativa Complessa (UOC) Reumatologia, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy.

Abstract

Objectives: Specific anti-inflammatory and/or immunomodulating drugs (AIDs) can influence endothelial function which is often impaired in patients with rheumatoid arthritis (RA). We sought to determine whether overall patterns of AID usage are similarly associated with endothelial function. Methods: The reactive hyperaemia index (RHI), a marker of microvascular endothelial function, was measured in 868 RA patients reporting their intake of seven AIDs known to affect endothelial function. Latent class analysis (LCA) was performed to characterise patterns of AID usage. Models for 2-6 classes were compared using the AIC and BIC statistics and Lo-Mendell-Rubin likelihood ratio tests. Associations between the classes and RHI were adjusted for age, gender, body mass index, diabetes, HDL-cholesterol, LDL-cholesterol, family history of ischaemic heart disease, smoking status, RA duration, DAS28 score, steroid dose, existing hypertension, and C-reactive protein. Results: LCA identified five distinct AID usage classes: Class 1, generally low medication usage; Class 2, using either sulfasalazine or non-tumour necrosis factor (TNF) inhibitors; Class 3, methotrexate users; Class 4, TNF-inhibitor users; and Class 5, hydroxychloroquine users. The geometric mean for the RHI for subjects in classes 1 to 5 was 1.92, 1.81, 1.94, 2.10, and 2.07, respectively, with subjects in classes 4 and 5 having better endothelial function than subjects in class 2 (p = 0.003 for each). The glucocorticoid dosage did not influence the classes formed or the association between the classes and the RHI in sensitivity analyses. Conclusion: There were five broad patterns (classes) of AID usage in RA patients. The RHI was relatively lower in users of either sulfasalazine or non-TNF inhibitors. TNF inhibitors or hydroxychloroquine may counteract the negative effects of RA on endothelial function.

Keywords: TNF-inhibitors; anti-inflammatory drugs; endothelial dysfunction; hydroxychloroquine; immunomodulating drugs; latent class analysis; rheumatoid arthritis.