Low Trough Adalimumab Linked to Secondary Treatment Failure in JIA

Adalimumab trough concentrations were found to be significantly lower in patients with juvenile idiopathic arthritis (JIA) with secondary failure compared with those with primary failure or those with an adequate response to adalimumab, according to study results published in Rheumatology.

Although adalimumab has been shown to improve disease outcomes in many patients with JIA, some patients have an inadequate clinical response to adalimumab due to the development of antidrug antibodies. According to prior evidence, low trough concentrations are associated with adalimumab failure but could be used to guide dosing and treatment intervals during targeted immunosuppressive therapy.

In the current retrospective cohort study, the researchers evaluated the association of adalimumab trough concentrations and response to adalimumab treatment in patients with JIA.

Patients with JIA who were visiting a children’s hospital in the Netherlands between 2011 and 2018 were included in the study. All patients were receiving adalimumab and had a failed treatment response to at least 1 disease-modifying antirheumatic drug (DMARD).

An adequate response to adalimumab was defined as a reduction of 50% or more in disease activity (measured using the clinical Juvenile Arthritis Disease Activity Score with a 71-joint count) within the first 3 months of therapy and disease inactivity or minimal activity at 6 months. Response to adalimumab treatment was categorized as adequate, primary failure (inability to achieve an adequate response), or secondary failure (an adequate response followed by an increase in disease activity).

Trough samples were collected within 48 hours prior to adalimumab administration and analyzed for adalimumab using a novel liquid chromatography tandem mass spectrometry assay and anti-adalimumab antibodies by radioimmunoassay.

A total of 34 patients with JIA and 35 trough samples were included in the analysis. Among the 34 patients, 16 were responders, 7 had primary failure, and 12 had secondary failure (1 patient had 2 trough samples with different results).

Median trough concentrations were significantly lower (P <.01) in patients with secondary failure (1.0 mg/L; interquartile range [IQR], 1.0-5.3 mg/L) compared with patients with an adequate response (14.94 mg/L; IQR, 10.31-16.19 mg/L) and those with primary failure (13.97 mg/L; IQR, 11.81-16.67 mg/L). In patients with trough concentrations of 5 mg/L or less, anti-adalimumab antibodies were detected in 73% (n=8/11), indicating that immunogenicity plays a role in trough concentrations of adalimumab.

Limitations of the study included a small sample size, the retrospective study design, and a lack of information on treatment compliance.

“Results suggest that trough concentration measurements could identify patients [with JIA] who require increased adalimumab doses to achieve or maintain therapeutic drug concentrations,” the researchers noted.

They concluded, “Results should be confirmed in prospective [pharmacokinetic and pharmacodynamic] studies, which are necessary to elucidate causes of inter-individual concentration variability, determine the most important variables associated with clinical outcome, and identify possible ‘pharmacological’ targets during adalimumab therapy.”

Reference

Doeleman MJH, de Roock S, El Amrani M, van Maarseveen EM, Wulffraat NM, Swart JF. Association of adalimumab trough concentrations and treatment response in patients with juvenile idiopathic arthritis. Rheumatology (Oxford). Published online April 20, 2021. doi:10.1093/rheumatology/keab354