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Immunogenicity of Anti-TNF-α Biotherapies: I. Individualized Medicine Based on Immunopharmacological Evidence.

Bendtzen K - Front Immunol (2015)

Bottom Line: Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use of protein drugs.The use of therapeutic strategies based on anti-TNF drug levels and ADA rather than dose-escalation has also proven to be cost-effective, as this allows individualized patient-tailored strategies rather than the current universal approach to loss of response.The objective of the present article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies.

View Article: PubMed Central - PubMed

Affiliation: Institute for Inflammation Research (IIR 7521), Rigshospitalet University Hospital , Copenhagen , Denmark.

ABSTRACT
Specific inhibition of the cytokine, tumor necrosis factor-α (TNF), has revolutionized the treatment of patients with several autoimmune diseases, and genetically engineered anti-TNF antibody constructs now constitute a heavy medicinal expenditure in many countries. Unfortunately, up to 30% of patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use of protein drugs. The use of therapeutic strategies based on anti-TNF drug levels and ADA rather than dose-escalation has also proven to be cost-effective, as this allows individualized patient-tailored strategies rather than the current universal approach to loss of response. The objective of the present article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies.

No MeSH data available.


Related in: MedlinePlus

Temporal association of circulating drug (infliximab) and ADA levels. Trough serum levels of infliximab and anti-infliximab antibody (ADA) were measured in 106 RA patients using radioimmunoassay. Infliximab was administered at a dosage of 3 mg/kg. Note the step-by-step disappearance of infliximab when ADA develop (44% of patients were ADA-positive after 6 months). With permission from Arthritis and Rheumatism (7).
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Figure 1: Temporal association of circulating drug (infliximab) and ADA levels. Trough serum levels of infliximab and anti-infliximab antibody (ADA) were measured in 106 RA patients using radioimmunoassay. Infliximab was administered at a dosage of 3 mg/kg. Note the step-by-step disappearance of infliximab when ADA develop (44% of patients were ADA-positive after 6 months). With permission from Arthritis and Rheumatism (7).

Mentions: It is known that trough serum levels of drug decline as soon as ADA appears. In many cases, the drug disappears completely as documented in RA patients treated with infliximab (Figure 1). Investigations of RA and CD patients have also shown that low serum levels of infliximab, adalimumab, and etanercept, and the presence of ADA correlate with the requirement for dose increase and therapeutic failure. Furthermore, serious side-effects that could be mediated by drug–ADA immune complexes have also been reported. These include infusion and allergic reactions, serum sickness, bronchospasm, arthus reactions, and vasculitis, some with fatal outcome (7, 12). In view of such findings, it is notable that the majority of patients still receive TNF-antagonists without attention to safety issues related to induction of ADA.


Immunogenicity of Anti-TNF-α Biotherapies: I. Individualized Medicine Based on Immunopharmacological Evidence.

Bendtzen K - Front Immunol (2015)

Temporal association of circulating drug (infliximab) and ADA levels. Trough serum levels of infliximab and anti-infliximab antibody (ADA) were measured in 106 RA patients using radioimmunoassay. Infliximab was administered at a dosage of 3 mg/kg. Note the step-by-step disappearance of infliximab when ADA develop (44% of patients were ADA-positive after 6 months). With permission from Arthritis and Rheumatism (7).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389569&req=5

Figure 1: Temporal association of circulating drug (infliximab) and ADA levels. Trough serum levels of infliximab and anti-infliximab antibody (ADA) were measured in 106 RA patients using radioimmunoassay. Infliximab was administered at a dosage of 3 mg/kg. Note the step-by-step disappearance of infliximab when ADA develop (44% of patients were ADA-positive after 6 months). With permission from Arthritis and Rheumatism (7).
Mentions: It is known that trough serum levels of drug decline as soon as ADA appears. In many cases, the drug disappears completely as documented in RA patients treated with infliximab (Figure 1). Investigations of RA and CD patients have also shown that low serum levels of infliximab, adalimumab, and etanercept, and the presence of ADA correlate with the requirement for dose increase and therapeutic failure. Furthermore, serious side-effects that could be mediated by drug–ADA immune complexes have also been reported. These include infusion and allergic reactions, serum sickness, bronchospasm, arthus reactions, and vasculitis, some with fatal outcome (7, 12). In view of such findings, it is notable that the majority of patients still receive TNF-antagonists without attention to safety issues related to induction of ADA.

Bottom Line: Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use of protein drugs.The use of therapeutic strategies based on anti-TNF drug levels and ADA rather than dose-escalation has also proven to be cost-effective, as this allows individualized patient-tailored strategies rather than the current universal approach to loss of response.The objective of the present article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies.

View Article: PubMed Central - PubMed

Affiliation: Institute for Inflammation Research (IIR 7521), Rigshospitalet University Hospital , Copenhagen , Denmark.

ABSTRACT
Specific inhibition of the cytokine, tumor necrosis factor-α (TNF), has revolutionized the treatment of patients with several autoimmune diseases, and genetically engineered anti-TNF antibody constructs now constitute a heavy medicinal expenditure in many countries. Unfortunately, up to 30% of patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use of protein drugs. The use of therapeutic strategies based on anti-TNF drug levels and ADA rather than dose-escalation has also proven to be cost-effective, as this allows individualized patient-tailored strategies rather than the current universal approach to loss of response. The objective of the present article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies.

No MeSH data available.


Related in: MedlinePlus