Identifying Predictors of MACE in Tofacitinib-Treated Rheumatoid Arthritis

After 24 weeks of tofacitinib, increased HDL-c, but not increases in LDL-c or total cholesterol, appeared to be associated with lower future major adverse cardiovascular event risk in patients with rheumatoid arthritis.

Results from a post-hoc analysis published in Arthritis & Rheumatology outlined risk factors for major adverse cardiovascular events (MACE) in tofacitinib-treated patients with rheumatoid arthritis (RA). Findings showed that traditional cardiovascular risk factors at baseline were associated with increased risk for future MACE; however, disease activity and inflammation measures were not.

Investigators pooled data from 6 phase 3 and 2 long-term extension studies conducted over 7 years. The current post-hoc analysis included all patients with RA who received ≥1 tofacitinib dose and had exposure after week 24; patients who experienced MACE prior to week 24 were excluded. MACE outcomes, adjudicated independently, comprised myocardial infarction, stroke, and cardiovascular death. Patient demographics and disease characteristics were assessed at enrollment. Traditional MACE risk factors were also captured at baseline, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). Cox regression models were used to evaluate associations between baseline variables and time to first MACE. Following 24 weeks of tofacitinib, changes in MACE predictors and time to future MACE were evaluated after adjusting for age, baseline values, and time-varying tofacitinib dose.

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The final cohort comprised 4076 patients, representing 12,873 patient-years of tofacitinib exposure. A total of 52 patients had adjudicated MACE, resulting in an incidence rate of 0.4 patients with events per 100 patient-years.

In univariable analyses, risk for MACE was significantly associated with older age (P <.0001), higher body mass index (P =.0066), statin use (P =.0020), and longer duration of RA (P =.0332). MACE was also associated with traditional risk factors, including elevated triglycerides (P =.0052), higher TC/HDL-c ratio (P =.0006), abnormal systolic (P =.0129) or diastolic (P =.0230) blood pressure, history of hypertension (P =.0002), and history of diabetes (P =.0146). Corticosteroid use was associated with a significantly lower risk for MACE (P =.0409), while disease activity and inflammation measures had no substantial association with MACE outcomes.

After adjusting for age, time-varying tofacitinib dose, and the baseline value for each variable, increases in HDL-c values (P =.0007) and decreases in TC/HDL-c ratio (P =.0450) after 24 weeks of tofacitinib were associated with a reduced risk for MACE. Elevated erythrocyte sedimentation rate also trended with an increased future risk for MACE. However, increases in TC levels and LDL-c levels were not associated with increased risk, nor were other measures of disease activity and inflammation.

As these analyses used data from studies not intended to evaluate MACE risk, results must be extrapolated with care. Even so, these data may assist clinicians in profiling tofacitinib-treated patients with RA at highest risk for future MACE.

Disclosure: This study was funded by Pfizer Inc. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.


Charles-Schoeman C, DeMasi R, Valdez H, et al. Risk factors for major adverse cardiovascular events in phase III and long-term extension studies of tofacitinib in patients with rheumatoid arthritis [published online April 17, 2019]. Arthritis Rheumatol. doi:10.1002/art.40911