TNFi use in RA tied to reduced VTE risk

Patients with rheumatoid arthritis (RA) treated with tumour necrosis factor (TNF) inhibitors may have a reduced risk of venous thromboembolism (VTE) compared with those treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), according to an observational study presented at EULAR 2020.

“By treatment with TNF inhibitors, the risk of major VTE events is reduced by almost half in comparison to csDMARDs,” said study lead author Dr Martin Schäfer from the German Rheumatism Research Center, Berlin, Germany.

The results were based on data from the RABBIT* register in Germany which tracks the disease course and biologic treatment in >17,000 patients with RA. The present study involved 11,094 patients who initiated a DMARD following insufficient response to a csDMARD. In this cohort, 3,500 were receiving csDMARDs (mean age 58.8 years, 73.6 percent female), 2,534 were receiving other biologic DMARDs (bDMARDs; mean age 58.1 years, 76.3 percent female), and 5,060 were receiving TNF inhibitors (mean age 56.5 years, 73.8 percent female). Mean RA duration was 6.2, 11.9, and 9.4 years in csDMARD, other bDMARD, and TNF inhibitor users, respectively.

Baseline C-reactive protein (CRP) levels were higher in patients on other bDMARDs (mean, 12.4 mg/L) or TNF inhibitors (mean, 11.6 mg/L) compared with csDMARDs (mean, 8.8 mg/L). Cardiovascular disease prevalence was also higher in patients on other bDMARDs or TNF inhibitors compared with csDMARDs (heart failure: 3.7, 2.2, and 1.0 percent, respectively; coronary artery disease: 7.2, 6.4, and 5.6 percent, respectively). bDMARD and TNF inhibitor recipients also had a higher incidence of osteoporosis than csDMARDs recipients (20.9, 15.2, and 11.4 percent, respectively), and were more likely to be receiving glucocorticoids (80.4, 78.1, and 73.3 percent, respectively). [EULAR 2020, abstract OP0012]

VTE events occurred in 1.1 percent of csDMARD or TNF inhibitor recipients and in 0.9 percent of patients on other bDMARDs. VTE risk was almost halved among TNF inhibitor compared with csDMARDs recipients (hazard ratio [HR], 0.53, 95 percent confidence interval [CI], 0.33–0.86). There was also a trend toward reduced VTE risk among other bDMARD compared with csDMARD recipients (HR, 0.66, 95 percent CI, 0.40–1.09).

Factors influencing a greater risk of VTE were older age at baseline (≥65 years; HR, 2.96, 95 percent CI, 1.94–4.52) and higher CRP levels (≥5 mg/L; HR, 2.09, 95 percent CI, 1.39–3.14), with an almost three- and twofold risk, respectively. In contrast, better physical function reduced VTE risk (HR, 0.85, 95 percent CI, 0.78–0.92 per 10 percentage point increase in full physical capacity).

Previous research has shown that VTE risk is increased in patients with RA. [Ann Rheum Dis 2014;73:1774-1780] “In the case of autoimmune diseases such as RA, the immune system turns against the body and causes inflammation in a number of places. Inflammation may have a disruptive effect on coagulation,” pointed out EULAR President Professor Iain McInnes from the University of Glasgow, Scotland, UK, who was not affiliated with the study.

“For patients with an increased risk of thrombosis, alternative treatment with TNF inhibitors, and possibly other biologic drugs, should be considered instead of standard csDMARD treatment,” noted co-author Dr Anja Strangfeld, also from the German Rheumatism Research Center. “Reducing the inflammatory activity is also an important factor to reduce the risk of VTE,” she added.