New test could predict arthritis drug failure in patients
A study of 311 patients by
The University of Manchester has found that it may be possible to
predict early which rheumatoid arthritis (RA) patients will fail to
respond to the biologic drugs given to treat them. These
findings could help better manage patients' symptoms.
RA is a chronic disease which affects up to 1.5% of the
population. It is a significant health burden for patients,
who can experience pain, reduced mobility and premature death
unless they receive effective treatment.
Biologics are a relatively new form of treatment for RA.
Given by injection, they work by stopping particular chemicals in
the blood from activating the immune system and attacking the
joints. Biologics are usually given in combination with an
anti-rheumatic, such as methotrexate, once the anti-rheumatic alone
is no longer effective.
Biologic drugs have dramatically improved the long-term health
of people with severe RA, reducing symptoms as well as joint damage
and disability. However, in about one in five patients the
treatment stops working after a few months - sometimes as a result
of anti-drug antibodies being formed - limiting their
In order to detect the antibodies and to measure the drug levels
in the bloodstream, previously it was thought that the testing to
detect the anti-drug antibodies and measure drug levels in the
bloodstream, would only be helpful if performed immediately before
the next dose of drug was due, when the drug levels are at their
lowest in the body.
This approach can be difficult to arrange in a clinical setting,
as patients take the drugs on different days and at different
The new study, funded by the Medical Research Council, Arthritis
Research UK and the NIHR Manchester Musculoskeletal Biomedical
Research Unit, shows that testing at random times is also effective
and makes it easier to use in a clinical setting.
Dr Meghna Jani, lead author of the work from the University's
Centre for Musculoskeletal Research, said: "Our study demonstrates
detecting low drug levels in rheumatoid arthritis patients on
adalimumab, one of the most commonly prescribed biologics, was the
strongest factor associated with non-response to treatment over 12
"This test is easy to perform in a hospital setting, and could
provide useful information on how to manage a patient whose
rheumatoid arthritis is not being controlled by adalimumab."
There were 311 patients included in the study, who provided
blood samples for testing at three, six and 12 months after
starting two different types of biologic drugs, adalimumab. The
research revealed that a total of 25% of patients on adalimumab
developed antibodies, but none were found in the patients using
The researchers also found that higher doses of methotrexate, a
drug often given together with the biologic treatment, was
associated with lower levels of drug antibodies, suggesting that
patients should be encouraged to continue methotrexate at the
highest dose they can tolerate, to reduce the risk of developing
Professor Anne Barton, a consultant rheumatologist at Central
Manchester University Hospitals NHS Foundation Trust and Director
of the Centre for Musculoskeletal Research at The University of
Manchester explained: "The next step will be to explore whether it
is cost-effective to use these tests routinely in clinical
practice, so that we can adjust treatments in those patients with
low drug levels and anti-drug antibodies."
The paper, 'Clinical Utility of Random Anti-TNF Drug Level
Testing and Measurement of Anti-Drug Antibodies on Long-Term
Treatment Response in Rheumatoid Arthritis' was published in the
journal Arthritis and Rheumatology.