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Biologics have been commonly prescribed as therapies for inflammatory bowel disease (IBD) since the late 1990s. However, research demonstrates that not all individuals respond to the first biologic taken and many lose response over time¹. As a result, there is a great need to explore the immunogenicity of IBD biologics. Studies indicate that measuring drug levels, free anti-drug antibodies, and total anti-drug antibodies of common IBD treatment biologics is a key component to unraveling immunogenic responses to biologics^2,3. ALPCO offers a comprehensive portfolio of colorimetric therapeutic drug monitoring assays to investigate the immunogenicity of IBD biologics. ALPCO’s TDM assays are simple to use and generate quality data for IBD researchers.

Investigating Immunogenicity of IBD Biologics

Therapeutic drug monitoring assays (TDM assays) can measure the drug, free anti-drug antibody (ADA), and total anti-drug antibody levels of common biologics classes used to treat IBD including TNF-alpha, integrin antagonists, and interleukin blockers. Drug level and ADA measurements can aid in the investigation of primary non-response (PNR) as well loss of response (LOR) to biologics therapies such as:

• Adalimumab
• Infliximab
• CT-P13 (infliximab biosimilar)
• Golimumab
• Vedolizumab
• Ustekinumab

Free Anti-Drug Antibody ELISAs

The measurement of free anti-drug antibodies with TDM assays allows for the semi-quantitative determination of unbound antibodies against a given biologic which enables an assessment of the immune system’s response to a given biologic. Free anti-drug antibody assays can be used to semi-quantitatively determine the unbound anti-drug antibodies against three TNF-alpha blockers:

• Adalimumab^*
• Infliximab^*
• Golimumab^*

The Free Anti-Drug Antibody ELISA plates are coated with biologic F(ab)2 fragments. Samples are added to the wells of the ELISA plate. Free ADAs in the samples are then captured by the F(ab)2 fragments on the plate. Antibodies which are already bound by a biologic in circulation do not have the ability to bind to the F(ab)2 fragments on the plate. Peroxidase-labeled biologic is added to the well and a TMB substrate allows for the colorimetric measurement of free ADAs in samples.

Total Anti-Drug Antibody ELISAs

The measurement of free and bound antibodies allows for the semi-quantitative determination of  total ADA levels in circulation. and can help explain whether or not antibodies are playing a role in  PNR and LOR to a given IBD biologic. Total anti-drug antibody assays can be used to semi-quantitatively determine the total anti-drug antibody levels of two common TNF-alpha blockers:

• Adalimumab^*
• Infliximab^*

Anti-drug antibodies can exist in both free form and bound to their corresponding biologic. When total ADA measurements are desired, the bound ADAs in the sample must first be displaced from the biologic. Next, anti-drug antibodies in the sample bind with peroxidase-labeled conjugate and biotinylated biologic in the well. Lastly, the biotinylated biologic binds to the streptavidin-coated plate, and a TMB substrate allows for the colorimetric measurement of total anti-drug antibody levels in the sample.

Drug Level ELISAs

Drug levels for biologics can be measured to help investigate the optimal concentrations of a given biologic. Understanding the optimal drug concentration can help avoid doses that are too low (ineffective) or too high (toxic). Drug level  assays can quantify levels of:

• Adalimumab^*
• Infliximab^*
• Golimumab
• CT-P13
• Vedolizumab
• Ustekinumab

The Drug Level ELISA plates are coated with monoclonal anti-drug antibodies. Samples containing free biologic and biologic bound to anti-drug antibodies are added to the ELISA plate wells. Free or unbound drug in the sample binds to the monoclonal ADA coated plate while the complexed drug is washed away. Lastly, peroxidase-labeled conjugate is added, and a TMB substrate allows for the colorimetric measurement of free drug levels in the sample. ALPCO offers therapeutic drug monitoring assays for investigating the immunogenicity of IBD biologics. Determining free anti-drug antibody and total anti-drug antibody levels allows for the analysis of primary non-response and loss of response to IBD biologics^1,2,3. Furthermore, measuring drug levels of biologics can help ^1,2,3. When used together, biologics and therapeutic drug monitoring assays  have the potential to uncover deeper insights that may guide the development of  new methods to  improve the lives of those living with inflammatory bowel disease. Shop TDM ELISAs for IBD Download our brochure to learn more about ALPCO's therapeutic drug monitoring assays for investigating the immunogenicity of IBD biologics. Download Brochure

References

1. Roda et al. (2016). Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clin Transl Gastroenterol. 2016 Jan;7(1):e135. doi:10.1038/ctg.2015.63. PMCID:PMC4737871.
2. Krishna et al. (2016). Immunogenicity to Biotherapeutics – The Role of Anti-drug Immune Complexes. Front Immunol. 2016;7:21. PMCID: PMC4735944.
3. Kopylov et al. (2014). Therapeutic drug monitoring in inflammatory bowel disease. Ann Gastroenterol. 2014;27(4):304-312. PMCID: PMC4188926.

  Unless otherwise noted, all assays are for Research Use Only in the U.S. and cannot be used in diagnostic procedures. ^*Health Canada Licensed.