Statins No Silver Bullet in RA

Statins have become a ubiquitous part of cardiovascular risk reduction. In addition to lowering cholesterol levels, statins have anti-inflammatory and immunomodulatory effects that the authors point out may be beneficial to patients with autoimmune disorders.

Hilda de Jong and colleagues in the Netherlands and the UK note that statins have multifactorial effects on immune-modulating cytokines and the expression of different immunological cells.¹ While statins promote some pro-inflammatory changes, such as a shift from T-helper-1 cell production to T-helper-2, they may also suppress the secretion of pro-inflammatory cytokines, such as interleukin (IL)-2, IL-12, interferon-γ, and tumor necrosis factor-α.

It is unclear whether statins increase or decrease the risk of rheumatoid arthritis (RA). Serving to confound the issue further is the fact that patients with RA are at higher risk for cardiovascular disease and thus are candidates for statin therapy. As such, hyperlipidemia could be implicated in RA risk rather than the statins used to treat it.

The authors examined the association between the use of statins and patterns of risk of developing RA over time; they also accounted for confounding by cardiovascular comorbidities. Recently, they presented their findings in PLOS One.

The study
The authors conducted a matched cohort study that looked at 511,620 statin users and 511,620 matched non-users from the Clinical Practice Research Datalink database in the UK. Primary outcomes consisted of a first diagnosis of RA or at least one prescription for a disease-modifying antirheumatic drug.

The results
• Overall incidence of RA was 4.2/10,000 person-years.

• No associations were found between RA and current (adjusted hazard ratio [HR_adj], 1.06; 99% confidence interval [CI], 0.88 to 1.27) or past statin users (HR_adj, 1.18; 99% CI, 0.88 to 1.57).

• The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level.

• Current users of statins saw increases in RA risk soon after starting the drug.

• After 1 year of statin exposure, the risk of RA declined to baseline level (> 1 year: HR_adj, 0.95; 99% CI, 0.74 to 1.16).

Implications for physicians
• Patients who started statin therapy had a 1.3-fold increased risk of developing RA during the first year of treatment.

• Monitor patients closely during the first year of statin treatment for signs and symptoms of RA.

• Ascertainment bias may be responsible for these findings, since closer monitoring usually follows the start of statin therapy.

• Be vigilant for an acceleration of RA disease onset, but reassure patients who remain healthy that their risk is no greater in the long term than that of patients who do not take statins.

References:

1. de Jong HJI, Cohen Tervaert JW, Lalmohamed A, et al. Pattern of risks of rheumatoid arthritis among patients using statins: a cohort study with the clinical practice research datalink. PLoS ONE. 2018;13:e0193297. doi.org/10.1371/journal.pone.0193297