Long-Term Benefits, Risks of Biologic Disease-Modifying Anti-Rheumatic Drugs in Patients with RA

At a recent 2017 EULAR press conference, researchers said that a Danish study demonstrated the incidence of RA-related TKR started to decrease after bDMARDs were introduced into their national treatment guidelines.⁵ This retrospective study showed the number of TKR surgeries in RA patients had been increasing at a rate of +0.19 per 1,000 person years before 2002, but dipped to -0.20 per 1,000 person years after 2003, when bDMARDs were introduced in Denmark. The incidence of THR in RA patients had been equivalent to -0.38 per 1,000 person years both before and after the introduction of bDMARDs.⁵

Although the same Danish researchers, using data from England and Wales in 2016, could not show a statistically significant reduction in THR, they demonstrated that introduction of bDMARDs was associated with a relative reduction of 34% in five-year rates of TKR since 2003.⁶

These studies demonstrated a reduction of TKR and THR in RA patients receiving biologic treatments despite the high cost of bDMARDs. The cost of biologics for RA patients can reach $30,000 annually, but the average cost for TKR is $44,816 for only the hospital procedure.⁷ Adding the costs of RA medical care, employer/caregiver and quality-of-life-related expenses, the annual cost of all patients living with RA can reach $40 billion U.S. annually.⁸

By using biologics in primary RA diagnosed patients, we can stabilize disease status and minimize indirect and overall medical costs due to surgeries and ER visits.

Positive Outcomes in CVDs

CV events are higher among patients with RA and other systemic inflammatory disease states regardless of progressive status.^9,10 The most common clinical cardiovascular event in RA patients is atherosclerosis. It is also important to evaluate CVDs’ clinical outcomes among potential treatment options in RA and other systemic inflammatory diseases. The most common therapeutic classes are NSAIDs, DMARDs, biologics and systemic corticosteroids.

Long-term, modest-dose corticosteroids and NSAIDs are contraindicated in RA patients with CVD comorbidities. The American Heart Association suggested clinicians avoid using NSAIDs in patients with history of CVD and limit the use of NSAIDs in all patient populations due to its mechanism of inhibiting both COX-1 and COX-2.^11,12 Long-term systemic corticosteroids also contribute to adverse cardiovascular events, including dyslipidemia and hypertension.¹³

Based on the 2016 EULAR recommendations for CVD management in RA patients, CVD risk decreases in RA patients with long-term use of bDMARDs, including TNF inhibitors, tocilizumab and rituximab.¹⁴ Chronic systemic inflammatory diseases clearly play a role in promoting the development of atherosclerosis due to actions on endothelial cells and leukocytes.¹⁵ A proposed mechanism by which anti-TNF therapies reduce CVD risk is through a reduction in the inflammatory cascade and signaling, eventually reducing athero­sclerosis and other cardiovascular events. The proposed mechanism of reducing CVD risk by tocilizumab and rituximab is their beneficial effect on carotid intima-media thickness, a surrogate marker for CVD.¹⁴