Adverse drug reactions represent a major health problem

Type A reactions are due to the pharmacological action of a drug, and type B reactions are mostly due to immunological effects. While the majority of type B reactions are rather harmless, some side effects are the cause of severe diseases and even death. Immunological side effects of drugs represnet indeed a main cause of drug withdrawal Drug induced hepatitis, toxic epidermal necrolysis, Guillain-Barré syndrome etc. do not only harm the individual patient, but can also cause an enormous loss of investment and money, as it is a relative frequent cause of “late” (after phase 3) drug withdrawals. Both, regulatory agencies as well as the pharmaceutical industries are interested to better recognize the potential of such side effects during drug development and possibly to predict and avoid such side effects. Development of such tests has been hampered by the rarity of severe side effects to a single drug, the lack of understanding their pathomechanism, the absence of animal models, and the lack of access to patients with drug hypersensitivity.

ADR-AC is based on

• a profound knowledge of the clinical picture and physiopathology of drug induced hypersensitivity reactions affecting different organs 
• an extensive experience with in vitro studies using cells from drug allergic individuals: these data adress T cell and basophil reactivity to drugs (small chemicals as well as biologicals) and allow to identify the causative drug in side effects
• the availability of a bank of peripheral blood mononuclear cells as well as serum from drug allergic individuals, which can be used as positive controls; these data are also necessary to choose the correct test in patients afected 
• a great battery of drug specific T-cell clones together with EBV transformed B cell lines from drug allergic donors: they help to better understand the drug reactivity of T cells, the crucial cell in drug allergic reactions 
• a steadily growing bank of mouse cell-hybridomas transfected with drug specific TCR able to recognize certain drugs and drug families in an MHC restricted way: this cell lines help in the understanding of TCR interactions with drugs
• Sophisticated basophil activation tests using serum of allergic donors to screen for drug activity in well defined basophile donors.

Identifying the culprit drug


Prof. Werner J. Pichler and his team at the Inselspital, University of Berne, Switzerland has studied the pathomechanism of drug allergies during the last 20 years. Combining careful clinical investigations with intensive research using blood and skin biopsies of drug allergic patients led to a better understanding of adverse side effects: a decisive role of T-cells in many immune mediated drug hypersensitivity reactions was found, cell mediated type IV reactions were subclassified and the p-i concept of T cell stimulation by drugs was developed.
This research has major implications for diagnosis of drug allergies: Over 10.000 diagnostic procedures like the lymphocyte transformation tests (LTT) were performed in patients with suspected drug hypersensitivity. Recently basophile activation tests for drugs were established. Both T cell and basophile based tests can also be used in the work up of patients with presumably allergic reactions to new drugs (phase 1-3 studies).

Identifying the culprit drug for a severe, potentially immune mediated side effect during drug development

During a phase 1-3 study or after launching the drug you are made aware that the drug might have caused a severe side effect. You want to know how you can handle this situation?

ADR-AC gives you advice: 

1. clinical evaluation of the case; 
2. work of the patient. We perform cellular or serological studies with the blood of the affected patients (and controls): this requires (details are provided upon request):

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