Biologic drugs and arrhythmic risk in chronic inflammatory arthritis: the good and the bad

Abstract

Increasing evidence indicates that patients with chronic inflammatory arthritis (CIA), including rheumatoid arthritis and spondyloarthropathies, have an increased risk of arrhythmic events, significantly contributing to the higher cardiovascular disease (CVD) morbidity and mortality observed in these subjects compared to the general population. Although the mechanisms accounting for such an arrhythmogenic substrate are not fully understood, the main role is probably played by chronic systemic inflammation, able to accelerate the development of structural CVD, as well as to directly affect cardiac electrophysiology. In the past decade, biologic therapies have revolutionized the treatment of CIA by highly enhancing the probability to effectively control disease activity and its systemic consequences, including cardiovascular involvement. Accordingly, accumulating data demonstrated that by potently inhibiting systemic inflammation, biologic drugs can reduce CVD progression and ameliorate arrhythmic risk parameters, with a putative beneficial impact on arrhythmia incidence. Nevertheless, a significant number of reports from clinical trials and postmarketing experience suggest that some of these medications, particularly TNF inhibitor monoclonal antibodies and rituximab, may in some circumstances precipitate arrhythmia occurrence, probably by acutely amplifying myocardial electric instability intrinsically associated with these diseases. In this review, we analyze the intricate link between biologic drugs and arrhythmias in CIA in the effort to identify which factors are involved in the fine-tuning of antiarrhythmic/pro-arrhythmic balance, and understand how this knowledge should be translated in the clinical practice to obtain the most favorable benefit-to-risk profile when biologic drugs are used in these patients.

Cardiovascular Manifestations of Inflammatory Bowel Disease: Pathogenesis, Diagnosis, and Preventive Strategies

“…Cyclosporine is associated with increased risk of hypertension, arrhythmias, acute coronary syndrome, and heart failure [132].…”

“…Biological molecules are associated with increased arrhythmogenic risks: supraventricular tachycardia, atrial fibrillation, ventricular tachycardia, multiple ectopic ventricular beats, bradyarrhythmias, and conduction disturbances [132]. Besides the arrhythmogenic risks, cardiovascular adverse effects include hypotension, hypertension, acute coronary syndrome, dyslipidemia, and worsening heart failure.…”

Prolonged P-Wave and QT Dispersion in Children with Inflammatory Bowel Disease in Remission

“…There are no significant documented pediatric data relating to QT alteration or fatal dysrhythmias with these drugs. About arrhythmogenic side effects of mesalamine and azathioprine, only few case reports in adult IBD patients are available in the literatures [21, 22]; however, a significant number of studies suggest that biologic drugs may increase the risk of arrhythmia in adult patients with inflammatory conditions [14, 23, 24]. In pediatric population, there is only one letter to the editor which is discussing cardiac involvement in 7 of 12 children with IBD during IFX therapy.…”

Novel clinical and therapeutic aspects in autoimmunity

“…Also, biologics may affect QTc and thus arrhythymias. Lazzerini et al [24] address the importance of arrhythmias associated with chronic arthritis and the controversial effects of anti-rheumatic therapies. Anti-TNF-a agents and tocilizumab have shown beneficial effects on the QT interval, as well as on cardiac autonomic dysfunction.…”