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:

• Empiric dose escalation: increasing the dose (eg, from 5 mg to 10 mg) as a first response to failure
• Testing-based strategy: relying on characteristics related to treatment failure to guide therapy; characteristics include pharmacodynamic (PD, presence of drug but lack of effect) or pharmacokinetic (PK, lack or absence of drug due to metabolism) conditions

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.

• Individuals with a rheumatic disease who have experienced failure of adalimumab or infliximab treatment

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.

• Measuring only drug levels may be appropriate if a sequential approach is preferred to concurrent testing. It may also be appropriate for therapeutic drug monitoring (TDM), though TDM is not routine for TNF blocker treatment because thresholds and testing intervals have not been established.
• Measuring only ADAs may be appropriate if insufficient bioavailability has already been established.
• Measuring both drug and ADA levels at the same time may expedite identification of the bioavailability of the drug and the cause of treatment failure.