When Is Switching Warranted Among Biologic Therapies in Rheumatoid Arthritis?

Alan Reynolds; Andrew S Koenig; Eustratios Bananis; Amitabh Singh


Expert Rev Pharmacoeconomics Outcomes Res. 2012;12(3):319-333. 

In This Article

Abstract and Introduction


Switching among biologic therapies is common practice in patients with rheumatoid arthritis who have an inadequate response or intolerable adverse events. Evidence from observational studies and association guidelines supports the use of sequential biologic therapy for these reasons. Owing to recent economic pressures on healthcare budgets, patients with rheumatoid arthritis who are well controlled on and tolerant of their current biologic therapy may be switched to alternative biologics, despite limited evidence supporting this practice. Clinical research and experience suggest that TNF antagonists are not interchangeable, as meaningful differences have been observed in their efficacy and safety profiles. Additional research is needed to assess the risk:benefit ratio of specific sequences of biologic therapies and the validity of switching biologic therapies for nonclinical purposes.


Over the past two decades, major paradigm shifts have occurred in the treatment of rheumatoid arthritis (RA), related in large part to the early institution of disease-modifying antirheumatic drugs (DMARDs) and the introduction of biologic agents, including tumor necrosis factor (TNF) antagonists, which have demonstrated unparalleled benefits.[1] The robust efficacy of the TNF antagonists adalimumab, etanercept and infliximab in RA has been confirmed in randomized controlled trials[2–4] and a recent meta-analysis,[5] yet sizeable proportions of patients discontinue anti-TNF therapy because they do not achieve an adequate response, subsequently lose response during therapy or experience adverse events.[6] Recent findings from national registries and other observational studies indicate that drug survival rates for TNF antagonists range from approximately 65 to 83% at 1 year, and discontinuations are due to primary or secondary nonresponse, or issues related to toxicity and tolerability.[7–13]

For patients who do not have a satisfactory response to an initial anti-TNF agent, rheumatologists may consider several alternative approaches, including: switching to a different TNF antagonist; switching to a biologic with a non-TNF-related mechanism of action; modifying concomitant synthetic DMARD therapy; reverting back to a previously prescribed synthetic DMARD; or introducing a synthetic DMARD to the regimen. Switching among TNF antagonists became a well-established practice with physicians' increasing familiarity with the clinical profiles of these agents and accumulating evidence of their benefits in slowing disease progression.[6] In a 2005 survey, 94% of rheumatologists reported switching patients from one TNF antagonist to another if they experienced an inadequate response or therapy-limiting adverse events.[14] However, switching among TNF antagonists has been reduced by the recent introduction of biologics with different mechanisms of action. Although the effects of using sequential anti-TNF agents have not been examined extensively in randomized controlled trials, several professional associations, including the American College of Rheumatology (ACR),[15] the European League Against Rheumatism (EULAR)[16] and the Consensus Group on Advances in Targeted Therapy,[17] recommend switching between TNF antagonists when the first agent is associated with an inadequate response or poor tolerability, based on evidence derived primarily from observational studies. In addition, data from published randomized controlled trials indicate that the non-TNF biologics rituximab, abatacept and tocilizumab are more effective than placebo in patients with an inadequate response to at least one TNF antagonist.[18–20]

Sequential use of TNF antagonists and switching to a different class of biologic agent are considered warranted for clinical reasons such as a lack or loss of efficacy or adverse events associated with initial anti-TNF therapy. However, patients receiving TNF antagonist therapy may also be switched to other therapies for nonclinical purposes. Although substitution for current treatments in patients who successfully achieve therapeutic targets may occur for many reasons, rapid growth of global healthcare expenditures and the substantial contribution of biologic agents to this growth have undoubtedly helped foster this practice. As little information is available on switching anti-TNF treatment in therapeutic responders, the health and cost consequences of this approach are not yet well understood.

The aim of this review is to assess the existing evidence that supports switching strategies for clinical and nonclinical reasons in patients who receive initial TNF antagonist therapy for RA.


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