CO:09:5 | LDL-cholesterol goal attainment with ezetimibe and bempedoic acid in patients with rheumatoid arthritis: a simulation study in the Italian CORDIS cohort

Alessandro Giollo¹, Kiren Khalid¹, Luca Bonanni², Nicola Ferri³, Gianluca Erre⁴, Matteo Piga⁵, Elena Bartoloni⁶, Andreina Manfredi⁷, Enno Giulio Favalli⁸, Maria Sole Chimenti⁹, Serena Guiducci¹⁰, Eleonora Celletti¹¹, Addolorata Corrado¹², Simone Parisi²⁰, Ivan Giovannini¹³, Elisa Gremese¹⁴, Garifallia Sakellariou¹⁵, Ombretta Viapiana¹⁶, Marco Fornaro¹⁹, Fabiola Atzeni¹⁷, Francesca Romana Spinelli¹⁸, Fabio Cacciapaglia¹⁹ | ¹Università di Padova Padova, Italy; ²UO Medicina Interna ULSS3 Mestre, Italy; ³Università di Padova, Department of Pharmaceutical and Pharmacological Sciences, University of Padova Padova, Italy; ⁴Università di Sassari Sassari, Italy; ⁵Università di Cagliari Cagliari, Italy; ⁶Univeristà degli studi di Perugia Perugia, Italy; ⁷Università di Modena e Reggio Emilia, UO di Reumatologia Ospedale Policlinico di Modena Reggio Emilia, Italy; ⁸IRCCS Humanitas Research Hospital, Rozzano Milano, Italy; ⁹Università Tor Vergata Roma, Italy; ¹⁰Università di Firenze Firenze, Italy; ¹¹Ospedale SS. Annunziata Chieti, Italy; ¹²Università degli studi di Foggia Foggia, Italy; ¹³Università di Udine, Clinica di Reumatologia Udine, Italy; ¹⁴Università degli studi di Milano Milano, Italy; ¹⁵Università degli Studi di Pavia Pavia, Italy; ¹⁶Università di Verona Verona, Italy; ¹⁷Università degli Studi di Messina Messina, Italy; ¹⁸Università La Sapienza Roma, Italy; ¹⁹Università di Bari, Reumatologia Universitaria Policlinico di Bari Bari, Italy; ²⁰S.C. di Reumatologia A.O.U. Città della Salute e della Scienza di Torino - Ospedale Molinette Torino, Italy

Background. Bempedoic acid (BA) is a novel lipid-lowering therapy (LLT) that reduces LDL cholesterol (LDL-C) when used in association with a statin or ezetimibe. Nevertheless, the potential of BA to achieve LDL-C targets in patients with rheumatoid arthritis (RA) has never been investigated.

Materials and Methods. We used a Monte Carlo simulation to mimic the sequential addition of ezetimibe and bempedoic acid in a large RA cohort. First, we determined whether patients were at their goal with current LLT based on their SCORE2 cardiovascular (CV) risk. The algorithm sequentially simulated the effect of adding ezetimibe 10 mg on LDL-C in patients who were not at goal at baseline with their current treatments (i.e., statins) and BA 180 mg in patients who did not achieve LDL-C goals after the simulated add-on of ezetimibe. The beta distribution was based on a mean (SD) of -22.9% (10%) and -16.7% (20.9%), respectively, for ezetimibe and BA. The simulation assumed no statin intensification beyond the baseline regimen. The probabilistic sampling was run 10,000 times on the complete set of patients. The mean LDL-C value and the number of patients at goal on each of the 10,000 simulated cohorts were calculated after ezetimibe and after BA simulation, applying national LDL-C goals. The LDL-C goal was achieved if the patient was below their LDL-C target for >50% of simulations.

Results. The study cohort included 1432 RA patients, mean (SD) age of 61 (10) years, 81.4% female, median disease duration of 120 months, and 70% RF/ACPA positive. 43.5% of patients were on glucocorticoids (mean prednisone-equivalent dose (SD) 4.9 (3.4) mg daily); 68.7% were on csDMARDs (80% on methotrexate), and 57.3% were on b/tsDMARDs. Disease activity was moderate, with a mean (SD) DAS28 of 3.4 (1.7) and CRP of 5.9 (10.2). Mean (SD) SCORE2 risk was 4 (3)%, with only 19% of patients on LLT. Most patients (77.6%) were not at LDL-C target, with 93% (at worst) not scoring their treatment goal in the very high-risk group and 48% (at best) in the low-risk group. Across all CV risk classes, BA showed an improvement in LDL-C targets (Figure 1). A higher impact of BA was seen in RA patients at low (patients at goal increased from 52 to 96%) and moderate (patients at goal increased from 24 to 85%) risk, while the effects of BA in patients at high and very high risk were less evident (Figure 2 and Table 1).

Conclusions. BA may be a promising therapeutic option for attaining CV risk goals in patients with RA, especially in those at low and moderate risk. These results must be confirmed from independent observational data.