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

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Two decades have passed since the first biologic disease-modifying anti-rheumatic drug (bDMARD) was approved. Studies on the long-term use of biologics in different disease states, such as for cardiovascular disease (CVD) and malignancy, as well as for knee/hip replacement, reveal some encouraging news.

In clinical trials, bDMARDs have been shown to increase the risk of infection and malignancy, but they are also known for better liver and kidney tolerance among patients with rheumatoid arthritis (RA) than synthetic DMARDs (sDMARDs). bDMARDs also have significant clinical benefits over sDMARDs when controlling moderate to severe autoimmune diseases caused by uncontrolled chronic inflammation, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis and polymyalgia rheumatica, but heretofore evidence is lacking that they reduce comorbidities in RA. The most common comorbidities among RA patients are CVD and joint damage.

A systematic literature review, which informed the 2016 update of the EULAR recommendations for RA management, studied the safety and efficacy of synthetic and biologic DMARDs in RA patients and showed that bDMARDs have favorable effects on CV events and total knee/hip replacement.¹

It’s worthwhile to review the long-term benefits and risks of biologics among RA patients and other chronic systemic inflammatory patient populations.

Per one study conducted in Sweden, total joint replacement surgeries are increasing in general, while the number of TKR & THR surgeries is decreasing in patients with a primary RA diagnosis. Introduction of biologics in RA patients may be an important contributing factor.

Benefits in Total Knee & Hip Replacements

Considering quality of life, one of the largest burdens for RA patients is total knee or hip replacement (TKR or THR) due to chronic joint damage. TKR and THR have increased in the general patient population with the aging of baby boomers. Prior to the introduction of biologics for RA patients, 25% of these patients would require TKR or THR within 10 years.² Per one study conducted in Sweden, total joint replacement surgeries are increasing in general, while the number of TKR and THR surgeries is decreasing in patients with a primary RA diagnosis.³ Introduction of biologics in RA patients may be an important contributing factor.

In 2014 in the U.S., researchers used data from the Nationwide Inpatient Sample, Health Care Cost and Utilization Project in a study that focused on the first three tumor necrosis factor (TNF) inhibitors: etanercept, infliximab and adalimumab (FDA approved in 1998, 1999 and 2002, respectively).⁴ In this study, patients were categorized into three subgroups: 1) RA as primary diagnosis, 2) RA as secondary diagnosis and 3) no RA. With a few exceptions, only the group of patients with RA as primary diagnosis were shown to have experienced an overall 32% and 24% reduction in TKR and THR surgeries, respectively, since 1993, and consistent decreasing rates after 2002.⁴