What is the evidence for a 'drug leakage' when switching patients from one biologic agent (e.g. adalimumab (Humira)) to another?

From the Guidelines

When switching patients from one biologic agent to another, it is recommended to change to a different mechanism of action, rather than switching within the same class, particularly after multiple TNF inhibitor failures, to minimize the risk of "drug leakage" and optimize treatment outcomes. The concept of "drug leakage" refers to the phenomenon where a patient who fails one biologic therapy may experience diminished response to subsequent biologics, particularly within the same class. This effect is most commonly observed when switching between TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, certolizumab) 1. Several observational studies suggest that the efficacy of a second TNF inhibitor is typically lower than the first, with response rates decreasing with each subsequent TNF inhibitor trial. For example, patients switching from adalimumab to another TNF inhibitor might experience approximately 30-50% lower response rates compared to biologic-naïve patients. The mechanism likely involves shared pathways of inflammation and potential cross-reactivity of anti-drug antibodies. Some key points to consider when switching biologics include:

• Monitoring drug levels and antibodies before switching can help guide more effective therapeutic decisions 1.
• Changing to a different mechanism of action, such as from a TNF inhibitor to an IL-17 inhibitor, may be beneficial in minimizing the risk of "drug leakage" 1.
• The use of biosimilars may also be considered, as they have been shown to have similar efficacy and safety profiles to their reference products 1.
• A treat-to-target strategy, with treatment adaptations within 6 months, may also be effective in optimizing treatment outcomes 1. In terms of specific recommendations, the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis suggests that bDMARDs should be used preferentially in combination with MTX or other csDMARDs, and that monotherapy is not a major recommendation 1. Overall, the evidence suggests that a thoughtful and individualized approach to switching biologics is necessary to optimize treatment outcomes and minimize the risk of "drug leakage".

From the Research

Evidence of Drug Leakage when Switching Biologic Agents

• There is limited direct evidence of "drug leakage" when switching patients from one biologic agent to another, as the provided studies focus on the effectiveness and safety of biologic agents in treating psoriasis and psoriatic arthritis, rather than the phenomenon of drug leakage itself 2, 3, 4, 5, 6.
• However, the studies suggest that switching biologic agents can be an effective treatment strategy for patients who experience primary or secondary failure, or adverse events, with their initial biologic therapy 3, 4.
• The decision to switch biologic agents is often based on factors such as the patient's risk profile, previous treatment experience, and the specific characteristics of the biologic agents being considered 2, 5.

Quantifying Drug Leakage when Switching Biologic Agents

• The provided studies do not quantify drug leakage directly, but they do report on the rates of adverse events, treatment discontinuation, and switching between biologic agents 2, 3, 4, 5.
• For example, a study by 3 reported that 53% of patients achieved PASI75 after 8 weeks of switching to a second biologic agent, and 89.4% achieved PASI75 after 16 weeks.
• Another study by 5 found that the overall drug survival rates for adalimumab, secukinumab, and ustekinumab in patients with psoriasis were 0.78,0.88, and 0.88, respectively, at 1 year.

Factors Influencing Drug Leakage when Switching Biologic Agents

• The provided studies suggest that factors such as psoriatic arthritis, previous biologic experience, and the specific characteristics of the biologic agents being used can influence the effectiveness and safety of biologic therapy 5, 6.
• For example, a study by 5 found that psoriatic arthritis predicted survival in the adalimumab and secukinumab cohorts, but predicted discontinuation in the ustekinumab cohort.
• Another study by 6 found that secukinumab demonstrated good efficacy across all outcomes in patients with psoriatic arthritis, and that all treatments for active PsA included in the analysis demonstrated superiority to placebo.