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Not only the presence of ADAb is a predictor of a non-response. Some non-responders have no detectable ADAb or have adequate or high drug levels without clinical response. In patients without detectable drug levels, however, no clinical effect of adalimumab was registered.<ref name=”[19]”>Ternant, D., Bejan-Angoulvant, T., Passot, C., Mulleman, D., Paintaud, G. (2015). Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis. ''Clinical Pharmacokinetics, 54''(11), 1107-1123. [https://doi.org/10.1007/s40262-015-0296-9 ''doi:10.1007/s40262-015-0296-9'']</ref><ref name=”[22]”>Pouw, M.F. et al. (2015). Key findings towards optimising adalimumab treatment: the concentration–effect curve. ''Annals of the rheumatic diseases, 74''(3), 513–518. [https://doi.org/10.1136/annrheumdis-2013-204172 ''doi:10.1136/annrheumdis-2013-204172'']</ref>
[[File:meandas28.png|left|thumb|Mean DAS28 improvement for adalimumab concentrations<ref name=”[22]”>Pouw, M.F. et al. (2015). Key findings towards optimising adalimumab treatment: the concentration–effect curve. ''Annals of the rheumatic diseases, 74''(3), 513–518. [https://doi.org/10.1136/annrheumdis-2013-204172 ''doi:10.1136/annrheumdis-2013-204172'']</ref>|500px]]
A good clinical response is characterized by a Disease Activity Score in 28 joints (DAS28) improvement of 1.2 and higher. Serum concentrations of around 3 mgµg/L mL are sufficient to reach this threshold. Serum levels up to 8 mgµg/L mL have a positive effect on the DAS28 score, therefore the probability of clinical response to adalimumab increases with the trough serum concentrations. It should be noted that serum levels surpassing 8 mgµg/L mL do not contribute to further clinical improvement. The cut-off value to distinguish between good responders and non and moderate of responders was determined to be 5 mgµg/LmL. Therefore, adalimumab serum trough concentrations in the range of 5-8 mgµg/L mL were found to be predictive of good clinical response. A DAS28 improvement score below 0.6 is classified as a no response.<ref name=”[22]”>Pouw, M.F. et al. (2015). Key findings towards optimising adalimumab treatment: the concentration–effect curve. ''Annals of the rheumatic diseases, 74''(3), 513–518. [https://doi.org/10.1136/annrheumdis-2013-204172 ''doi:10.1136/annrheumdis-2013-204172'']</ref>
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== Medical Use and TDM ==
The drug is supplied as a solution for injection with a pH of 5.2. Current available dosage forms are 40 mg/0.8 mL, 40 mg/0.4 mL, 20 mg/0.4 mL and 10 mg/0.2 mL single-use prefilled syringe. There also exist prefilled pens of 40 mg/0.8 mL and 40 mg/0.4 mL.<ref name=”[4]”>Medsafe (2012). Humira solution for injection: Data Sheet. Accessed on 6 November 2018, at [http://www.medsafe.govt.nz/Medicines/SearchResult.asp ''http://www.medsafe.govt.nz/Medicines/SearchResult.asp''].</ref> It is administered once every week or every other week. The target steady state trough concentration is between 5 and 8 mgµg/mL.
In current practices, when the concentration of adalimumab is at a normal range, but the patient has no decreased disease activity, the patient can be classified as non-responding. A switch to a different medicine could be beneficial. When serum levels of adalimumab are too low, the underlying cause, either non-compliance or ADAb, is investigated. If the concentration is not extremely low, an increase of dosage can be considered.
Measurements of adalimumab levels are not routinely done. Therapeutic drug monitoring (TDM) is the practice of measuring the concentration of a specific drug in the bloodstream with the aim of using this data to optimize the individual dosing schemes of patients. TDM could provide a means to optimize the treatment with adalimumab. The introduction of a biosensor for adalimumab as a means for TDM would allow for better drug monitoring. It gives the possibility to detect non-responders in an early stage of treatment or to optimize dosing strategies. For patients with too high serum levels, dosage reduction to obtain serum levels between 5 and 8 mgµg/L mL could be beneficial for the patient as the expensive drug is used more optimally. As ADAb can be the cause of the lower adalimumab serum levels, measurement of ADAb with a biosensor is also a possibility. However, as adalimumab can interfere with an assay that measures ADAb, measurement of adalimumab itself is to be prefered.<ref name=”[22]”>Pouw, M.F. et al. (2015). Key findings towards optimising adalimumab treatment: the concentration–effect curve. ''Annals of the rheumatic diseases, 74''(3), 513–518. [https://doi.org/10.1136/annrheumdis-2013-204172 ''doi:10.1136/annrheumdis-2013-204172'']</ref>
A treatment based on TDM has the potential to ensure a maximal clinical benefit with the lowest dose of the drug.<ref name=”[22]”>Pouw, M.F. et al. (2015). Key findings towards optimising adalimumab treatment: the concentration–effect curve. ''Annals of the rheumatic diseases, 74''(3), 513–518. [https://doi.org/10.1136/annrheumdis-2013-204172 ''doi:10.1136/annrheumdis-2013-204172'']</ref> Next to the health benefit, treatment could have an economic benefit, as it can be cost-saving in the long-term, especially in the case of dose reduction.
