INDIVIDUAL TEST 129,135,130

Simponi® (golimumab)

129 - Concentration

Indication

As an aid in monitoring treatment efficacy, drug concentrations can be established and hereby help optimizing individual patient treatment strategy.

Test result

Result is given as concentration of the biologic TNF-α inhibitor. Limit of detection: 0.65 µg/mL.

Method

The assay is performed with an in vitro reporter cell line (iLite) which measures the amount of drug in the serum that can inhibit TNF-α binding to the TNF receptor on the cells (Lallemand 2011).

The specific TNF-alpha binding activates a reporter gene (Firefly Luciferase) and the effect of the produced enzyme can be measured.

The method is very stable and reproducible and is based on an arrest of the normal cell cycle. The cellular activity assay has a very good correlation to classical concentration measurement by radioimmunoassay (RIA) but measures in contrary to binding assays the activity of the drug, which is of a high therapeutic significance and clinical value.

Result interpretation

Normal or high concentration of active drug but no treatment effect is observed in patients with a profile of the disease that is not driven by TNF-α levels. When secondary failure is suspected despite the presence of normal or high concentrations of active drug, the sample may have been collected not at Cmin. (through level)

When the concentration of the TNF-α inhibitor is below the detection level, less than 0.65 µg/mL, this may be caused by NAbs (neutralizing anti-drug-antibodies) against the TNF-α inhibitor which prevents the drug to bind to TNF-α. (Determination of NAbs is done in a separate analysis.) Patient compliance problems may be the reason when the serum concentration of TNF-α inhibitors is lower than expected in combination with undetectable levels of NAbs or ADA (non-neutralizing anti-drug-antibodies). Low drug concentration and no treatment effect may also suggest that the patient needs a higher drug dose to achieve the desired therapeutic effect. Low concentrations of the drug can also be due to non-neutralizing ADA. ADAs can both limit the bioavailability (with local administration of the drug) and increase the elimination of the drug in the circulation. (Determination of ADAs is done in a separate analysis.)

130 - Neutralising antibodies (NAbs)

Indication

Monitoring the effect of the drug can determine if the patient develops neutralizing anti-drug antibodies (NAbs) that target the drug.

Test result

Test results for NAbs to TNF-α inhibitors are reported as negative or positive with titer. Testing for NAbs against TNF-α inhibitors are performed only when the concentration of TNF-α inhibitors activity in serum is < 0.65 µg/mL.

Method

The assay for TNF-α inhibitor NAbs is based on the same in vitro reporter cell line (iLite) which is used to measure the activity (concentration) of the drug (Lallemand 2011). In short, the NAbs tests show if antibodies in patient serum can prevent TNF-α inhibitor activity in an in vitro cell model.

Result interpretation

NAbs are defined as antibodies that prevent TNF-α inhibitor binding and thus makes the treatment ineffective.

In case of a secondary treatment failure and positive results for NAbs, it is highly recommended to change the drug treatment.

When it is uncertain if the NAbs cause treatment failure, the patient should be followed up with regular monitoring, since there is a high risk that NAbs sooner or later will affect the efficacy of the TNF-α inhibitor.

NAbs do not cross-react between the different TNF-α inhibitors.

135 - Anti-drug antibodies (ADA)

Indication

When the patient has measurable, but low, concentration of drug in the blood (0.65 - 10 µg /mL) we can offer a test to verify if the patient has developed ADA (anti-drug antibodies).

Test result

The test results are reported as negative or positive.

Method

The test is an enzyme immuno assay (EIA) for the determination of antibodies binding to TNF-α inhibitors in serum. The procedure can be described as a sandwich EIA. Prior to analysis, serum is treated with acid and diluted to allow dissolution of immune complexes.

Result/interpretation

ADAs can both limit the bioavailability (with local administration of the drug) and increase the elimination of the drug in the circulation. ADAs do not cross-react between the different TNF-α inhibitors.

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Monitoring of biopharmaceuticals

ENSKILD ANALYS 129,135,130

Simponi® (golimumab)

129 - Concentration

Indication

As an aid in monitoring treatment efficacy, drug concentrations can be established and hereby help optimizing individual patient treatment strategy.

Test result

Result is given as concentration of the biologic TNF-α inhibitor. Limit of detection: 0.65 µg/mL.

Method

The assay is performed with an in vitro reporter cell line (iLite) which measures the amount of drug in the serum that can inhibit TNF-α binding to the TNF receptor on the cells (Lallemand 2011).

The specific TNF-alpha binding activates a reporter gene (Firefly Luciferase) and the effect of the produced enzyme can be measured.

The method is very stable and reproducible and is based on an arrest of the normal cell cycle. The cellular activity assay has a very good correlation to classical concentration measurement by radioimmunoassay (RIA) but measures in contrary to binding assays the activity of the drug, which is of a high therapeutic significance and clinical value.

Result interpretation

Normal or high concentration of active drug but no treatment effect is observed in patients with a profile of the disease that is not driven by TNF-α levels. When secondary failure is suspected despite the presence of normal or high concentrations of active drug, the sample may have been collected not at Cmin. (through level)

When the concentration of the TNF-α inhibitor is below the detection level, less than 0.65 µg/mL, this may be caused by NAbs (neutralizing anti-drug-antibodies) against the TNF-α inhibitor which prevents the drug to bind to TNF-α. (Determination of NAbs is done in a separate analysis.) Patient compliance problems may be the reason when the serum concentration of TNF-α inhibitors is lower than expected in combination with undetectable levels of NAbs or ADA (non-neutralizing anti-drug-antibodies). Low drug concentration and no treatment effect may also suggest that the patient needs a higher drug dose to achieve the desired therapeutic effect. Low concentrations of the drug can also be due to non-neutralizing ADA. ADAs can both limit the bioavailability (with local administration of the drug) and increase the elimination of the drug in the circulation. (Determination of ADAs is done in a separate analysis.)

130 - Neutralising antibodies (NAbs)

Indication

Monitoring the effect of the drug can determine if the patient develops neutralizing anti-drug antibodies (NAbs) that target the drug.

Test result

Test results for NAbs to TNF-α inhibitors are reported as negative or positive with titer. Testing for NAbs against TNF-α inhibitors are performed only when the concentration of TNF-α inhibitors activity in serum is < 0.65 µg/mL.

Method

The assay for TNF-α inhibitor NAbs is based on the same in vitro reporter cell line (iLite) which is used to measure the activity (concentration) of the drug (Lallemand 2011). In short, the NAbs tests show if antibodies in patient serum can prevent TNF-α inhibitor activity in an in vitro cell model.

Result interpretation

NAbs are defined as antibodies that prevent TNF-α inhibitor binding and thus makes the treatment ineffective.

In case of a secondary treatment failure and positive results for NAbs, it is highly recommended to change the drug treatment.

When it is uncertain if the NAbs cause treatment failure, the patient should be followed up with regular monitoring, since there is a high risk that NAbs sooner or later will affect the efficacy of the TNF-α inhibitor.

NAbs do not cross-react between the different TNF-α inhibitors.

135 - Anti-drug antibodies (ADA)

Indication

When the patient has measurable, but low, concentration of drug in the blood (0.65 - 10 µg /mL) we can offer a test to verify if the patient has developed ADA (anti-drug antibodies).

Test result

The test results are reported as negative or positive.

Method

The test is an enzyme immuno assay (EIA) for the determination of antibodies binding to TNF-α inhibitors in serum. The procedure can be described as a sandwich EIA. Prior to analysis, serum is treated with acid and diluted to allow dissolution of immune complexes.

Result/interpretation

ADAs can both limit the bioavailability (with local administration of the drug) and increase the elimination of the drug in the circulation. ADAs do not cross-react between the different TNF-α inhibitors.

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