TNF Inhibitors Cut Odds of VTE in RA Patients

Maureen Salamon

June 08, 2020

The risk for venous thromboembolism is almost 50% lower in patients with rheumatoid arthritis (RA) taking TNF inhibitors than in those taking conventional synthetic disease-modifying antirheumatic drugs (DMARDs), according to data from the German RABBIT registry.

"Some rheumatologists have thought TNF inhibitors could increase the risk for venous thromboembolism events, but we don't think this is true, based on our findings," said investigator Anja Strangfeld, MD, PhD, from the German Rheumatism Research Center in Berlin.

The risk is more than one-third lower in RA patients treated with other newer biologics, such as abatacept, rituximab, sarilumab, and tocilizumab.

However, risk for a serious venous thromboembolism is twice as high in patients with C-reactive protein (CRP) levels above 5 mg/L and is nearly three times as high in patients 65 years and older.

For the study, Strangfeld and her colleagues followed about 11,000 patients for more than 10 years. The findings were presented at the European League Against Rheumatism (EULAR) 2020 Congress.

"Patients with RA have a greater risk for venous thromboembolism compared with the general population, but we didn't know the risk conveyed by different DMARD treatments," Strangfeld told Medscape Medical News. "It is also evident that higher age and lower capacity for physical function increase the risk, which was not so surprising."

Chronic inflammation in RA patients elevates the risk for deep vein and pulmonary thrombosis by two to three times, said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR scientific program committee.

Among the supporting studies Isaacs discussed during an online press conference was a Swedish trial of more than 46,000 RA patients, which had been presented earlier by Viktor Molander, a PhD candidate from the Karolinska Institute in Stockholm (abstract OP0034).

Molander's team showed that one in 100 patients with high disease activity will develop venous thromboembolism within a year, which is twice the number of events seen among patients in remission.

Combined with the RABBIT data, both studies "show if you can control their disease in the right way, you're not only helping rheumatoid arthritis patients feel better, but you could be prolonging their lives," Isaacs said.

The prospective RABBIT study followed RA patients who began receiving a new DMARD after treatment failed with at least one conventional synthetic DMARD, such as methotrexate or leflunomide. At baseline, those taking TNF inhibitors or other biologics had higher CRP levels on average, as well as a higher rate of existing cardiovascular disease. They also received glucocorticoids, such as prednisone, more often.

The observational nature of the RABBIT study is a weakness, Strangfeld said, and it could not prove cause end effect. But the methodology had several strengths, including input on patient factors from participating rheumatologists at least every 6 months.

"We enrolled patients at the start of treatment and observed them, regardless of any treatment changes, for up to 10 years," she added. "That's a really long observation period."

The TNF inhibitors are actually reducing the inflammation and, therefore, reducing the risk.

The RABBIT data can help shape treatment decisions, said Loreto Carmona, MD, PhD, from the Musculoskeletal Health Institute in Madrid, who is chair of the EULAR abstract selection committee.

For a woman with RA who smokes and takes oral contraceptives, for example, "if she has high levels of inflammation, I think it's okay to use TNF inhibitors, where maybe in the past we wouldn't have thought that," she said.

"The TNF inhibitors are actually reducing the inflammation and, therefore, reducing the risk," Carmona told Medscape Medical News. "It could be an effect of using the drugs on people with higher levels of inflammation. It's an indirect protective effect."

The study was funded by a joint unconditional grant from AbbVie, Amgen, BMS, Fresenius-Kabi, Hexal, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. Strangfeld is on the speakers bureau of AbbVie, BMS, Pfizer, Roche and Sanofi-Aventis. Isaacs is a consultant or has received honoraria or grants from Pfizer, AbbVie, Amgen, Merck, Roche, and UCB. Carmona has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) 2020 Congress: Abstract OP0012. Presented June 3, 2020.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.