Trough Levels, Drug Antibodies Predict Suboptimal Response to As-Needed Infliximab in SpA

Trough infliximab levels and anti‐drug antibodies may reliably predict a suboptimal response to low-dose, as-needed infliximab in patients with spondyloarthritis (SpA), according to research published in the International Journal of Rheumatic Diseases.

Adult patients with SpA (n=35; 80% men) between June 2015 and December 2016 were included in the cohort for this cross-sectional, analytical study. Patients were diagnosed with SpA according to the Assessment in Spondyloarthritis International Society classification criteria for axial and/or peripheral SpA, and received at least 3 infliximab infusions (3 mg/kg to 5 mg/kg) 6 to 12 months prior to the start of the study; mean infliximab dose was 4.05±0.43 mg/kg/infusion and number of infusions ranged from 3 to 31.

Study participants reported and graded back, neck, and hip pain, peripheral joint pain, and global disease activity on a scale of 0 to 10. Ankylosing Spondylitis Disease Activity Scores-erythrocyte sedimentation rate/C-reactive protein (ASDAS-ESR/CRP) scores were calculated in order to obtain patients’ measure of disease activity.

Within the study population, mean serum tumor necrosis factor-alpha levels were 38.9±29.03 pg/mL, and cytokine levels correlated positively with ASDAS-ESR and ASDAS-CRP scores (rₛ=0.273 and rₛ=0.296; P =.11 and P =.08, respectively).

Infliximab antibodies were present in 68.58% of patients. Mean trough infliximab levels were significantly lower in patients who were antidrug antibody positive compared with patients who were antidrug antibody negative (0.89±0.46 μg/mL vs 1.92±1.31 μg/mL; P =.002).

Patients who were antidrug antibody positive also had significantly higher ASDAS scores. Treatment with concomitant methotrexate decreases the chance of antidrug antibody detection but was not statistically significant (odds ratio 0.4; P =.23). Mean trough infliximab level in the study was 1.21±0.93 μg/mL, and a significant negative correlation between trough infliximab levels and measures of disease activity was noted (ASDAS-ESR, rs=-0.578; ASDAS-CRP, rs=-0.534).

The researchers of the study concluded, “Collectively, our data set indicate that both the presence of antidrug antibodies and low trough infliximab levels are associated with high disease activity scores.” Additionally, the researchers propose “that during a suboptimal response to infliximab, the measurement of trough drug levels and antidrug antibodies could potentially be used to make treatment decisions, that is change of biologic vs dose escalation. However, the therapeutic benefit and cost-effectiveness of such a strategy [need] to be evaluated in larger studies.” 

Disclosures: Drs Upadhyaya, Handa, and Gupta report relationships with Janssen. For a complete list of disclosures, please see the full text of the study online.

Reference

Patil A, Upadhyaya S, Dawar R, et al. Anti-drug antibodies and low serum trough infliximab levels correlate with disease activity measures in spondyloarthritis patients on an as-needed infliximab treatment [published online June 18, 2019]. Int J Rheum Dis. doi:10.1111/1756-185X.13636