Effect of introducing biologics to patients with rheumatoid arthritis on the risk of venous thromboembolism: a nationwide cohort study

Abstract

In the United States, 100,000–300,000 patients die from venous thromboembolism (VTE) each year, with more than 500,000 people related hospitalizations. While in Europe, 500,000 people die from VTE each year. Patients with rheumatoid arthritis are at increased risk of VTE. The use of biologics in patients with rheumatoid arthritis may be associated with an increased risk of VTE. We identified all patients who had been newly approved for Catastrophic Illness Card of rheumatoid arthritis extracted the claims data from the National Health Insurance research database and Registry for Catastrophic Illness Patient Database from 2003 to 2016. VTE was defined as the presence of inpatient VTE diagnostic codes (including DVT or PE) according to the discharge diagnosis protocol. An analysis of VTE variables indicated that the incidence of VTE in the biologic group (14.33/10,000 person-years) was higher than that in the conventional drug group (12.61/10,000 person-years). As assessed by the Cox proportional hazards model, the relative HR for VTE in the biologic group (HR: 1.11; 95% CI 0.79–1.55) versus that in the conventional drug group did not reach a significant difference. In conclusion, this study found no significant differences in risk were observed between the use of conventional DMARDs and biologics.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

“…From a total of 2961 references (after de-duplication), 226 were selected for a full-text review and 59 observational studies fulfilled the inclusion criteria 16–74. In addition, 2 RCTs with a primary safety outcome,2 3 and 28 RCTs/LTEs from the efficacy SLR,75–102 were included (flow chart in online supplemental figure S1).…”

“…Of 59 observational studies, 51 assessed only 1 outcome,16–66 and 8 addressed ≥2 outcomes (online supplemental table S1–137). 67–74 Of 27 studies evaluating the risk of infections,27–47 67 69 71–74 23 included patients on bDMARDs,27–29 31–33 35–37 39–47 69 71–74 9 of which also patients on JAKi,27 28 30 31 42 45 69 71 72 3 only patients on csDMARDs34 38 67 and 1 patients either on tofacitinib or on csDMARDs 30.…”

“…Nine studies evaluated the risk of malignancies with bDMARDs,48–53 71 73 74 and one of these also with tofacitinib 71. Thirteen studies assessed the risk of MACE,17–24 67–71 with 11 including patients on bDMARDs,17–21 23 24 67 69–71 6 of which included patients on JAKi20 21 24 67 69 71 and 2 had patients only on csDMARDs 22 68. Intestinal perforations25 26 and neuroinflammatory events60 61 were assessed in two studies, each in patients on bDMARDs.…”

Venous Thromboembolism in Rheumatoid Arthritis: The Added Effect of Disease Activity to Traditional Risk Factors

“…71 bDMARDs have not been linked to an increased risk of VTE in RA. 56,[72][73][74][75] In a large Chinese cohort studying the risk of VTE with bDMARDs compared to csDMARDs, there was no statistically significant association between biologic use and VTE (HR, 1.11 (95% CI 0.79-1.55); (p > 0.05). 72 In another cohort study on the risk of VTE and TNFi use, there was no significant association between TNFi and VTE (HR of TNFi group was 0.8).…”

“…56,[72][73][74][75] In a large Chinese cohort studying the risk of VTE with bDMARDs compared to csDMARDs, there was no statistically significant association between biologic use and VTE (HR, 1.11 (95% CI 0.79-1.55); (p > 0.05). 72 In another cohort study on the risk of VTE and TNFi use, there was no significant association between TNFi and VTE (HR of TNFi group was 0.8). 74 The significant effect of JAKi on different cytokine pathways may hypothetically reduce the risk of thrombosis.…”