How to monitor anti-TNF-alpha therapy (infliximab and adalimumab)?

Anti-TNF alpha drugs are members of the relatively new therapeutic class of biopharmaceuticals or biologics. Their use is becoming increasingly wide-spread, with 70 000 patients receiving treatment in France and an expenditure of 1 billion Euro.

These are chimeric or human monoclonal antibodies that block the action of TNF alpha, a major pro inflammatory cytokine. Marketing authorization has been granted for the treatment of rheumatoid arthritis, chronic inflammatory diseases of the intestines (Crohn’s disease and ulcerative colitis), spondyloarthritis and psoriasis.

Their use is currently positioned as a second-line treatment for when “conventional” treatment, for example methotrexate in rheumatoid arthritis or azathioprine in Crohn’s disease, is not adequately effective. The recommendation is to combine conventional treatment and a biologic.
The main contraindications are active infection, latent tuberculosis, cancer and heart failure.

In consideration of their high therapeutic efficacy, their high cost, and the small number of products available, it is essential to optimize their use to decrease the rate of loss of patient response, which currently occurs in approximately 20% of annual cases, in part due to the development of anti-drug antibodies.

Levels of anti-TNF alpha correlate positively with clinical response. Similarly, the presence of antibodies targeted against anti-TNF alpha is associated with a loss of clinical response. These levels are subject to multiple influences:

• height, weight and sex
• posology, injection schedule, concomitant use of immunosuppressants
• serum concentrations of albumin and CRP
• serum concentration of TNF alpha
• presence and levels of potential antidrug antibodies

Monitoring of these levels, alongside clinical response, makes it possible to adjust treatment by increasing or decreasing the medication doses, or by switching drugs to another anti-TNF alpha product or another therapeutic class (other than anti-TNF alpha).

Infliximab (Remicade® and its biosimilars: Inflectra® and Remsima®) is administered by means of IV infusion in a hospital setting.

Adalimumab (Humira®) is administered by subcutaneous injection by a nurse or by the patients themselves.

Monitoring

The blood sample should be collected before a new injection.
The frozen serum is sent to the laboratory together with the clinical information sheet “R46”, available on our website.
The assays, performed using the Lisa Tracker kit from Theradiag, include parallel quantification of the drug and potential antibodies, as well as interpretation.

Example of the report

Measurement of infliximab and antiinfliximab antibodies (Remicade®, Inflectra®, Remsima®) – Lisa Tracker® kit

• Residual level of infliximab: 0.7 ?g/mL     3.0-7.0
• Anti-infliximab antibodies: < 10.0 ng/mL    <10.0

Recommendation

• Low infliximab levels, without thepresence of anti-infliximab antibodies.
• Please consider treatment optimization.