The use of anti-TNF biologicals in the treatment of rheumatoid arthritis has been a major therapeutic advance. A recent article about testing for drug immunogenicity in these patients by a national reference lab, ARUP, was intriguing (see: Dancing Through the Pain: Advancements in Immunogenicity Testing Deliver Relief to Patients with Autoimmune Diseases). Below is an excerpt from it:
To manage the overproduction of TNF seen in rheumatoid arthritis, patients are prescribed TNF blockers, medications that suppress the response to TNF and decrease inflammation. What happens is the body starts seeing the medication as a foreign element, triggering the immune system to create antibodies to eliminate it. This is called immunogenicity. This happens in about half of the patients.....TNF blocking drugs don’t always work because the body may see them as foreign invaders, producing antibodies against them that make the drugs ineffective. Testing for drug levels of biologicals help clinicians figure out if the drug is still working for the patient and if it is being administered at the right dose..... [W]hen a patient has been responding to a drug, then stops all of sudden, the physician wants to know why. If the patient has developed antibodies against the drug, the physician may switch them over to another type of TNF blocking drug. There are five of them available in the United States, with one biosimilar recently approved. When the patient develops antibodies against the TNF blocker, it is important to switch to another drug, as the patient could end up with an immune-complex disease that threatens the organs.....Immunogenicity testing may also reveal that there are no drug antibodies present, indicating that the patient may require a higher dosage....[T]he most commonly used tests measure the presence of any antibody that can bind to the drug molecule, regardless of whether or not they interfere with drug activity. The ARUP test only detects the presence of those antibodies that inhibit the function of the drug, which makes it more specific for identifying the cause as to why the drug treatment is not working.
Immunogenicity can be divided into wanted and unwanted (see: Immunogenicity). The latter is defined in the following way:
Unwanted immunogenicity is an immune response by an organism against a therapeutic antigen (ex. recombinant protein, or monoclonal antibody). This reaction leads to production of anti-drug-antibodies (ADAs) inactivating the therapeutic effects of the treatment and, in rare cases, inducing adverse effects. The prediction of the immunogenic potential of novel protein therapeutics is thus a challenge in biotherapy.
Here's more information from the ARUP web site about Adalimumab (Humira) activity and the neutralizing antibody to it:
This test is used to evaluate secondary response failures to adalimumab therapy. Secondary response failure is defined as loss of clinical response after initial improvement of clinical signs and symptoms. Therapeutic decision should rest on both the clinical response and the knowledge of the fate of the drug including the emergence of immunogenicity in individual patients. Circulating adalimumab levels have been shown to vary considerably between patients. These differences relate to route and frequency of administration and patient-related features such as age, gender, weight, drug metabolism, and concomitant medications such as methotrexate and other immunosuppressants.