Early Low Blood Levels of Humira and Antibodies Against It Predict Therapy’s Failure, Study Says

Low levels of Humira (adalimumab) early in the course of treatment and the presence of neutralizing autoantibodies in the blood of people with ankylosing spondylitis (AS) are associated with failure to respond to this treatment, a study says.

The study, “Early adalimumab and anti-adalimumab antibody levels for prediction of primary nonresponse in ankylosing spondylitis patients,” was published in the journal Clinical and Translational Science.

Abbvie‘s Humira is an antibody that blocks the activity of a pro-inflammatory molecule called tumor necrosis factor alpha (TNF-alpha). This molecule is produced in excessive amounts in people with AS. For that reason, Humira is frequently prescribed to them to reduce inflammation, damage, and joint pain.

However, Humira is not effective in 30% to 40% of all AS patients. The reasons why these people fail to respond to Humira are not fully understood, but low levels of the medication and anti-adalimumab antibodies (AAA) may be partly responsible. (The production of AAAs in a person block the activity of Humira, rendering the medication ineffective.)

To assess if these two factors could predict patients’ responsiveness to this treatment, investigators analyzed clinical data on 31 people with active AS, all using Humira as part of their treatment regimen at the First Affiliated Hospital of Soochow University in China.

The researchers also studied the concentration and effect relationship of Humira, or the link between the concentration of a therapy and its effectiveness.

All were being given Humira by under the skin (subcutaneous) injection every other week, and were examined by a physician at baseline (study start) and after completing two, four, eight, and 12 weeks of treatment.

Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score (ASDAS) or the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at all these time points. Humira responders were defined as those with a 2 or more point reduction in ASDAS since baseline, and those with a less pronounced drop since the study’s start but a minimum of a 1.1 point reduction by week 12.

Levels of Humira and its autoantibodies in the blood were measured in all participants.

From the 31 patients enrolled in the study, 12 (38.7%) failed to respond to treatment and 21 (67.7%) were positive for AAAs.

Humira was not detectable in any sample at baseline. Over the course of the study, treatment levels were consistently higher in patients without AAAs, compared to those who were positive for these autoantibodies.

Statistical analyses also revealed that disease activity tended to ease with increasing levels of the medication, reaching a maximum reduction with 8-12 μg/mL of Humira in blood serum.

Failure to respond to treatment was also strongly linked to lower blood levels of Humira (lower than 9.82 μg/mL) at week 12.

The investigators also found that patients whose levels of the therapy dropped below 3.37 μg/mL at week two, or 4.28 μg/mL at week four, would likely remain under 9.82 μg/mL at week 12 and not respond to treatment.

“[O]ur findings confirm the existing concentration-effect relationship of adalimumab [Humira] in patients with AS and provide evidence that lower early adalimumab levels and higher early AAA levels predict primary nonresponse,” the researchers wrote.

“These results indicate that adalimumab and AAA levels taken at an early stage may help physicians to prevent [using an] ineffective therapy,” they added.