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TNF Blockers for Rheumatic Diseases: Drug and Anti-drug Antibody Levels: Laboratory Support of Management
- Interpretive Guide
- Related Tests
Clinical Focus |
TNF Blockers for Rheumatic Diseases: Drug and Anti-drug Antibody Levels |
Laboratory Support of Management |
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Tumor necrosis factor (TNF) blockers, such as adalimumab (Humira®) and infliximab (Remicade®), are used to treat rheumatic diseases (eg, rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis) and inflammatory bowel disease (IBD; Crohn disease, ulcerative colitis).1,2 TNF blockers have had a major impact on the therapy of these conditions, but response rates vary by indication (Table 1) and other factors (eg, dose). Many patients do not initially respond (primary failure), while others respond initially but do not maintain the response (secondary failure). Table 1. Rates of Nonresponse to TNF Blockers for Treatment of Rheumatic Diseases
When treatment fails, a physician may need to consider other treatment options, such as adjusting dose or dosing interval, switching to a different TNF blocker, or switching to a non-TNF blocker. Selecting a treatment option depends on the strategy being used by the physician. Strategies for addressing treatment failure include the following:
In one study, investigators used a decision-making model to compare these approaches in rheumatoid arthritis patients. In the model, each month of suboptimal treatment increased costs (mostly attributed to drug and visit costs) and the interval of follow-up visit varied from 3 to 6 months. The model showed that a testing-based strategy saved costs when it prevented nonoptimal treatment in as little as 2.5% to 5% (6- and 3-month follow-up, respectively) of patients.3 With a testing-based strategy, measuring adalimumab or infliximab drug levels can help differentiate PD from possible PK conditions associated with treatment failure. The presence of therapeutic drug levels can indicate PD conditions, whereas subtherapeutic drug levels can indicate PK issues, such as increased drug clearance or patient adherence issues. PK issues can be managed by higher dose, shortening the dosing interval, or addressing patient adherence.4,5 On the other hand, loss of response after induction (PD) is usually due to the formation of antibodies against the drug (anti-drug antibodies [ADAs]).4,6 Testing for ADAs can help determine if changing the treatment approach is appropriate. ADAs can cause subtherapeutic drug levels. They form in about 25% of infliximab-treated and 14% of adalimumab-treated patients.7 In patients who have subtherapeutic drug levels and test positive for ADAs, switching to a different TNF blocker may be more effective than increasing dose. In patients who have subtherapeutic drug levels and test negative for ADAs, increasing dose or addressing adherence issues may be appropriate. |
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Quest Diagnostics offers tests for the TNF blockers adalimumab and infliximab for patients with rheumatic diseases (Table 2). All tests use enzyme-linked immunosorbent assays (ELISA) to measure levels. Table 2. Available Tests for TNF Blockers for Rheumatic Diseases
Testing for drug levels will indicate bioavailability, whereas testing for ADAs can help differentiate causes of insufficient bioavailability.
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Studies suggest a target trough concentration of 5 to 12 µg/mL for adalimumab8 and 2 to 8 µg/mL or 2 to 10 µg/mL for infliximab.3,9 Subtherapeutic drug levels may be caused by a patient not yet achieving a steady state trough level early in therapy; they may also be caused by inadequate dosing, a dosing interval that is too long, or accelerated drug clearance. Accelerated drug clearance may be explained by ADAs or rheumatoid factor (RF) in the patient's serum or by other diseases that indirectly lead to immunoglobulin loss (eg, kidney disease, protein-losing gastroenteropathy). Adalimumab or infliximab ADA levels ≥10 AU indicate detectable serum levels, which can lead to accelerated drug clearance, reduced trough levels, and a compromised clinical response. Levels <10 AU are considered "not detected" and suggest treatment failure is not caused by ADAs. Some ELISA-based tests for adalimumab or infliximab ADAs are susceptible to false-negative results caused by cross-reactivity with RF. However, Quest Diagnostics uses ELISAs that measure both free and bound ADAs, so serum RF will not cause false-negative results. Table 3 contains result interpretation and management strategies when both drug and ADA levels are tested. Table 3. Interpretation of Results in Patients with TNF Blocker Treatment Failure4
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Content reviewed 12/2017 |
* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.