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ADA-lab. KI/CMM

Laboratory for research and analysis of anti-drug antibodies (ADA) at Karolinska Institutet (KI) and Center for Molecular Medicine (CMM)

Biopharmaceuticals are becoming increasingly important as treatment, especially for patients with severe chronic illnesses. Unfortunately, the immune system reacts against parenterally administered drugs (those given as injections or infusions) and anti-drug antibodies (ADA) might develop. High titers of ADA can block the intended treatment effect and the patient might need to switch treatment to ensure continuous control over the disease. All biopharmaceutical drugs have the potential to activate the immune system, but to what degree depends on the type of drug, formulation, dose, route and frequency of administration, as well as characteristics of the patient and disease. The clinical relevance of ADA depends on the titer, the neutralizing capacity and if they are transient or persistent.

For new drugs and biosimilars the pharma industry needs to provide the regulatory agencies with an evaluation specifying how immunogenic a drug preparation is and what percentage of the patients treated in the clinical trial developed the ADA. These data are unfortunately not directly transferable into clinical practice, which usually consist of a more diverse population of patients subsequently treated over longer periods. In order to guarantee that all patients have the desired effect of their treatment over time, we need to know if their immune system is reacting towards the treatment or not in regular health care practice.

We can measure the ADA and drug levels with various immunological assays and thus at an early stage identify those patients that have lost the effect of the treatment. Our ambition is to, together with the health care system, implement, follow up and review processes whereby we can transfer ADA testing to the health care routine for those patients that are treated with biological drugs and to do research on the potential clinical impact of immunogenicity.

We provide tests for the following biopharmaceuticals:

Neutralizing ADA (nADA or NAb) against interferon beta (IFNbeta) by a bioassay (iLite, Eurodiagnistica, Malmö)

  • Screening for nADA against IFNbeta: 3125 SEK
  • Screening and titration of nADA against IFNbeta (for the around 20% expected to become positive): 5000 SEK

ADA against natalizumab (Tysabri) by ELISA (BiogenIdec, ”bridging” ELISA)

  • Screening of ADA against Tysabri: 2500 SEK

Analysis of ADA against rituximab (Mabthera) by electrochemiluminiscens (ECL) on the Meso Scale Discovery (MSD) platform

  • Screening (ADA, pos/neg): 3000 SEK
  • Screening and titration of ADA positive samples: 6000 SEK

From November 2007 the test results of the ADA analyses for MS patients are registered in the Swedish MS registry. You can register MS patients and download referral forms from this home page, which is part of the Swedish Neuroregister:

Swedish Neuroregister

Referral forms can also be downloaded directly from here:

Interferon beta nADA referral form

Tysabri (natalizumab) referral form

Mabthera (rituximab) referral form

For other patient groups than MS, the test results will be sent by paper to the address of the clinic noted on the referral form.

For patients treated with TNF blocking drugs, we recommend to start with screening of drug level in trough by ELISA that can be ordered through the TakeCare system and which is done by Clinical Immunology at the Karolinska University Hospital. Samples with very low trough level of drug (<0.2 µg/ml) will be tested for ADA by ELISA at Clinical Immunology at the Karolinska University Hospital. Samples with low drug level but above 0.2 µg/ml might have a suboptimal effect due to immune complexes formed between the drug and the ADA. These can be detected by the PandA method using ECL on MSD at the ADA lab. KI/CMM and ordered through this referral form:

PandA infliximab referral form

You are welcome to send in your samples!

Associate professor Anna Fogdell-Hahn, Dr. Katharina Fink (MD/PhD) and professor Jan Hillert

Publications:

Rituximab (Mabthera and MS)

28762877

IFNbeta ADA and MS

26779831

28729851

28170401

27806057

24444338

22551640

20837854

20534645

18727672

18535018

17911184

17439886

Natalizumab (Tysabri) ADA and MS

23045379

23390173

21511692

21228027

Review articles:

26098690

25959571

24780058

Anti-drug antibodies.
Warnke C, Hermanrud C, Lundkvist M, Fogdell-Hahn A.
Drugs and Therapy Studies 2012; volume 2:e11