Abstract
Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent had failed in this open-label observational study. These patients were all treated with a second biologic agent and 27 ultimately required treatment with a third. The response to the therapy and disease activity were assessed at 6 and 12 months after each switch. Results: The remission rates at 6 months were lower than previously reported and the initiation of a second biologic agent resulted in significant improvement at 12 months, including DAS remission in 36% of patients. The response in those receiving a third biologic was less pronounced, as might be expected in this relatively treatment-refractory population. In this group, only patients treated with tocilizumab had maintained remission at one year. Conclusion: Patients who do not respond to an anti-TNF agent often benefit from being switched to a second, or even third, biologic. Importantly, it may take longer than expected to fully assess the effectiveness of a second or third agent in patients with refractory disease.
Highlights
Introduction iationsThe treatment of rheumatoid arthritis (RA) has changed greatly in recent years due to the introduction of biologic therapy
Recommendations regarding changing from one biologic to another rely on expert consensus opinion [24,25,26] and there is even less data available to guide the management of patients who have failed to respond to multiple biologic agents
This study confirms that patients who failed to respond to the initial biologic therapy with an anti-TNF agent may obtain a significantly beneficial response after switching to a second, or even third, drug
Summary
The treatment of rheumatoid arthritis (RA) has changed greatly in recent years due to the introduction of biologic therapy. These agents target intercellular signaling pathways, co-stimulatory molecules, cytokines, or specific cell populations and can induce a significant therapeutic response, leading to improved signs and symptoms of disease as well as slowing or preventing structural damage [1]. Clinical trials and observational studies have shown that 50–70% of RA patients respond to biological therapy, according to ACR and EULAR criteria [2,3,4,5,6,7,8]. With the recent approval of novel agents with differing mechanisms of action, there are a number of treatment options available after the failure of the first biologic.
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