Changes

Jump to: navigation, search

Adalimumab

637 bytes added, 10:09, 13 May 2019
no edit summary
|-
!style="text-align:left;"|Synonyms
|ADL,<br />D2E7,<br />adalimumab-adaz,<br />adalimumab-adbm,<br />adalimumab-atto<ref name="[1]" />
|-
!style="text-align:left;"|Type
|-
!style="text-align:left;"|Molecular weight
|144190.3 Da148 kDa<ref name="[1]" />
|-
!style="text-align:left;"|Half life
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>
{| class="wikitable" style="border: none; background: none;"
== 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 ADL 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, a patient can be classified as a non-reponder, 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 beneficialis often advised. 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.
== State of the art of adalimumab assays ==
At the moment, there are no handheld or table-top point-of-care devices for detecting adalimumab available on the market. In the table below, a selection of the available adalimumab assays is listed.
{| class="wikitable" style="margin-bottom:0"
!Sample Volume
!Reportable range
!Dilutionratio*
!Precision
!Incubation time
|5 μL
|1–30 µg/mL
|1:200199<br />1:15001499<br />1:20001999|Total: CV <15%<br /> Inter-assay: CV <15.4%
|2 hours 10 min.
|-
|R-Biopharm AGapDia<ref name=”[28]”>RIDASCREEN ADM Monitoring apDia Adalimumab ELISA (2016). Leaflet ''RIDASCREEN ADM MonitoringapDia Adalimumab ELISA.'' R-Biopharm AGapDia.</ref>|G09043710201|RIDASCREEN ADM MonitoringapDia Adalimumab ELISA
|10 μL
|0.5-12 µg/mL<br />2.0- 48 µg/mL
|1:10099<br />1:400399|Intra-assay: CV <10.1%<br />Inter-assay: CV<14.2%
|1 hour 40 min.
|-
|5 μL
|0.3 - 16 µg/mL
|1:201200|Intra-assay: CV <13.3%<br />Inter-assay: CV<9.7%
|2 hours
|-|R-Biopharm AG<ref name=”[30]”>GN3043 RIDA®QUICK ADM Monitoring (2018). Leaflet ''GN3043 RIDA®QUICK ADM Monitoring''. R-Biopharm AG.</ref>|GN3043|RIDA®QUICK ADM Monitoring|20 μL|0.5 - 25 μg/ml|1:499|Intra-assay: CV < 16.8%<br />Inter-assay: CV< 16.6%|15 min.|-|BÜHLMANN<ref name=”[31]”>LF-TLAD25 Quantum Blue® Adalimumab (2018). Leaflet ''LF-TLAD25 Quantum Blue® Adalimumab''. BÜHLMANN.</ref>|LF-TLAD25|Quantum Blue® Adalimumab|10 μL|1.3 - 35 μg/mL|1:19|Intra-assay: CV < 28.6%<br />Inter-assay: CV < 12.6%|15 min |}<div style="margin-bottom:1em"><sub>''Table 2: Selection of currently available systems for measuring adalimumab.''<br />*Note: the dilution ratio is defined as 1:x, with x the volume of added reagents relative to the volume of plasma sample</sub></div>
To determine the trough levels of adalimumab, the samples must be taken within 24 hours prior to the drug administration.<ref name=”[27]”>MabTrack level adalimumab (2018). Leaflet ''MabTrack level adalimumab''. Sanquin.</ref>
These assays are sandwich-type assays with enzymatic labelling, except for the RIDA®QUICK ADM Monitoring and Quantum Blue® Adalimumab, which are based on lateral flow immunoassays. Mabtrack by Sanquin uses polystyrene microtiter wells with immobilized TNF-specific mouse monoclonal antibodies. These bind recombinant TNF. The adalimumab that is present in the sample bind binds to the bound TNF on the microtiter plate and a an adalimumab/TNF/anti-TNF complex is formed. Next, a monoclonal ADAb labeled with horseradish peroxidase is added which binds to the complex. A substrate solution leads to the formation of a colored product, proportional to the amount of adalimumab present in the sample.<ref name=”[27]”>MabTrack level adalimumab (2018). Leaflet ''MabTrack level adalimumab''. Sanquin.</ref> The RIDASCREEN ADM Monitoring Adalimumab ELISA and LISA-TRACKER Adalimumab both have immobilized TNF-⍺ on the surface of the microwell plate. While RIDASCREEN ADM the apDia Adalimumab ELISA makes use of ADAb conjugated with horseradish peroxidase to form a TNF-⍺/adalimumab/conjugated-ADAb complex, the LISA-TRACKER uses anti-human IgG biotinylated antibodies to form the complex, whereafter horseradish peroxydase labelled with streptavidin is added that binds to the complex.<ref name=”[28]”>RIDASCREEN ADM Monitoring apDia Adalimumab ELISA (2016). Leaflet ''RIDASCREEN ADM MonitoringapDia Adalimumab ELISA.'' R-Biopharm AGapDia.</ref><ref name=”[29]”>LTA002 LISA-TRACKER Adalimumab (2017). Leaflet ''LTA002 LISA-TRACKER Adalimumab''. Theradiag.</ref>
== Numbers ==
Rheumatoid arthritis affects around 1% of the world population per year.<ref name=”[3032]”>Marita Cross, M. et al. (2014). The global burden of rheumatoid arthritis: estimates from the Global Burden of Disease 2010 study. ''Annals of Rheumatic diseases, 73'', 1316-1322. [https://doi.org/10.1136/annrheumdis-2013-204627 ''doi:10.1136/annrheumdis-2013-204627'']</ref> Global estimates in 2010 reported a prevalence rate of 0.35% for women and 0.13% for men. The prevalence of RA is higher in more developed countries.<ref name=”[3133]”>Fazal, S.A. et al. (2018). A Clinical Update and Global Economic Burden of Rheumatoid Arthritis. ''Endocrine, Metabolic &amp; Immune disorders - Drug Targets, 18''(2), 98-109. [https://doi.org/10.2174/1871530317666171114122417 ''doi:10.2174/1871530317666171114122417'']</ref> A study in the US reported an overall lifetime risk for RA of 3.6% for women and 1.7% for men. This corresponds to around 1 in 28 women and 1 in 59 men that will develop RA in their lifetime.<ref name=”[3234]”>Crowson, C.S. et al. (2011). The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. ''Arthritis and Rheumatism, 63''(3), 633-639. [https://doi.org/10.1002/art.30155 ''doi:10.1002/art.30155'']</ref>
Globally in 2010, RA represented 0.49% of years lived with disability (YLD) and 0.19% of disability-adjusted-years (DALY). Across 31 nations in the period of 2009–2011, a total of 219,189 patients died, in whom RA was registered as the underlying cause of death. The YLDs for RA were 55/100000 population and the total DALYs were around 4.8 million.<ref name=”[3133]”>Fazal, S.A. et al. (2018). A Clinical Update and Global Economic Burden of Rheumatoid Arthritis. ''Endocrine, Metabolic &amp; Immune disorders - Drug Targets, 18''(2), 98-109. [https://doi.org/10.2174/1871530317666171114122417 ''doi:10.2174/1871530317666171114122417'']</ref>
The US reported having approximately $128 billion of direct and $47.0 billion of indirect costs billable to arthritis and related rheumatic conditions. In the UK, this number came down to £560 million a year in health care costs.<ref name=”[3133]”>Fazal, S.A. et al. (2018). A Clinical Update and Global Economic Burden of Rheumatoid Arthritis. ''Endocrine, Metabolic &amp; Immune disorders - Drug Targets, 18''(2), 98-109. [https://doi.org/10.2174/1871530317666171114122417 ''doi:10.2174/1871530317666171114122417'']</ref>In 2017, adalimumab (Humira) was at the top of pharmaceutical products by sales worldwide. The drug generated more than 18.4 billion US dollars. Almost twice as much as Rituxan, who took second place with 9.2 billion dollars generated.<ref name=”[3335]”>Statista (2018). Top 15 pharmaceutical products by sales worldwide in 2017. Accessed on 7 November 2018, at [https://www.statista.com/statistics/258022/top-10-pharmaceutical-products-by-global-sales-2011/ ''https://www.statista.com/statistics/258022/top-10-pharmaceutical-products-by-global-sales-2011/''].</ref> In 2015, Humira cost costs around $2669 per month in the US and $1362 in the UK.<ref name=”[3436]”>Statista (2018). Average prices of Humira in selected countries in 2015. Accessed on 7 November 2018, at [https://www.statista.com/statistics/312014/average-price-of-humira-by-country/ ''https://www.statista.com/statistics/312014/average-price-of-humira-by-country/''].</ref>
== References ==
<references />

Navigation menu