New research suggests high levels of drug antibodies and patients not taking medication as instructed are associated with low drug levels leading to poor treatment response

New research published in the Annals of the Rheumatic Diseases journal suggests that high levels of drug antibodies and inadequate patient adherence are associated with poor response to biologic drug treatment in rheumatoid arthritis (RA) patients.

Biologic drugs used to treat RA act by targeting chemicals that cause inflammation in the body. They are usually very effective but, in about one in five patients where biologics work initially, the treatment stops working a few months later. In some cases, this is thought to be due to the body producing antibodies to the biologic drug and interfering with how it acts. Antibodies are proteins produced by the body to protect against foreign substances.

Previous research has discovered that when antibodies are detected against older biologic drugs (adalimumab and infliximab); subsequent low drug levels are associated with loss of response to the medication. Newer biologic drug, Certolizumab, has a different structure to traditional biologics and is now commonly used.

In a study led by Dr Meghna Jani, Centre for Musculoskeletal Research at The University of Manchester, scientists wanted to assess a number of factors: the frequency of antibodies in certolizumab-treated RA patients; the link between antidrug antibodies, drug levels and treatment outcomes, and clinical factors associated with antibodies and drug levels over 12 months.

The study included 115 patients with RA, who provided blood samples after starting certolizumab within the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS).

37% of patients on certolizumab developed antibodies, higher than other estimates with other biologic drugs such as adalimumab using similar sensitive methods (~25%) in the same study.

Researchers found the high levels of antibodies were linked to the patient having less of the drug in their system, which in turn was linked to poor treatment outcome.  Interestingly patients who developed the antibodies were more likely to have more swollen joints before starting the biologic.

Apart from drug antibodies, the most important factor linked with certolizumab drug levels, was whether patients take their medication as prescribed.

The study also established the levels of certolizumab in the body that make it more likely for patients to respond well to the treatment.  It was shown that the testing can be carried out in blood samples taken at random times rather than just before the next dose of biologic drug is due using sensitive methods for detection.

Anne Barton, Professor of Rheumatology and BRU Inflammatory Arthritis in Adults Theme Lead, said: “The findings confirm that measurement of drug levels in patients with RA treated with certolizumab could be helpful in the management of RA.

The ability to predict which patients are unlikely to respond at an early stage of biologic treatment using these tests could mean that patients are switched to the right drug as soon as possible.

This research was supported by the NIHR Manchester Musculoskeletal Biomedical Research Unit.