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

The literature shows a positive correlation between severity of RA and the risk of both non-Hodgkin’s lymphomas (NHL) and Hodgkin’s lymphoma (HL), and it is believed that immunological elements can trigger transformation of normal lymphocyte polyclonal population into lymphoproliferative disease.^25,26 Severe RA has a higher risk of lymphoma than the general population. In general, the risk ratio for lymphoma in RA patients is 2.0, and the hazard ratio for lymphoma in RA patients receiving bDMARDs falls into the range of 2.3–5.⁹, which is not significantly different from RA patients receiving sDMARDs per EULAR safety recommendations.^1,27 Per these summarized data, there is no clear evidence that RA lymphoma risks are increased by bDMARDs.

Per new EULAR safety recommendations, the risk of melanoma may be slightly increased in patients receiving bDMARDs compared with sDMARDs with an adjusted HR of 1.5.1 However, a recent malignancy risk study conducted in Australian RA patients showed that melanoma risk was increased in both TNFi-treated and biologic-naive RA patients compared with the general population, with a standardized incidence ratio (SIR) of 2.72 and 2.03, respectively.²⁸

Conclusion

An evaluation of the long-term risks and benefits of using bDMARDs suggests that bDMARDs have more statistically significant clinical benefits in the areas of total joint replacement and CVD risk in RA patients. Malignancy should not be a barrier for RA patients to receive bDMARDs, as long as patients are under close monitoring by both rheumatologists and oncologists. Based on current studies, bDMARDs showed significant value clinically, but work still needs to be done to show significant long-term economic value. Future studies should be designed to demonstrate comprehensive and clear clinical roles of bDMARDs in heterogenous diseases, such as CVD.

Nan Yang, PharmD, is a one-year postgraduate employed by Evergreen Pharmacy in West Allis, Wis.

Kurt Oelke, MD, is the clinical studies director at the Rheumatic Disease Center in Glendale, Wis.

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