Higher trough levels of infliximab are clearly associated with clinical responses across the spectrum of rheumatic and other inflammatory diseases including ankylosing spondylitis. However, in the studies reviewed, data are not sufficiently clear and are highly heterogeneous making it difficult to accurately quantify and characterize responsiveness to infliximab and recommend monitoring in ankylosing spondylitis.
These findings by Reyes Serrano Gimenez, M.D., of Valme University Hospital in Seville, Spain are featured in the July 17 issue of the British Journal of Clinical Pharmacology.
Dr. Gimenez states, “In our opinion, the results from included studies are very heterogeneous. It is necessary to design larger studies, with the doses usually used in these diseases and appropriate administration interval, to prove the relationship between infliximab concentrations and the improvement of activity disease in order to determine whether therapeutic drug monitoring could be considered as a useful tool in this context. “
Tumor necrosis factor inhibitors such as infliximab have shown great promise in treating chronic inflammatory diseases such as spondyloarthritis. However, treatment failure in as many as 40 percent of patients concerns researchers for the possibility of anti-drug antibodies, which may lead to ineffective serum drug concentrations.
The authors performed a review of the literature in an effort to explore the relationship of serum infliximab concentrations with disease activity in spondyloarthritis.
Other studies have highlighted the importance of disease activity and highly intra- and inter-individual variability in serum anti tumor necrosis factor drug concentrations, underscoring the importance of finding adequate monitoring parameters.
With regards to monitoring infliximab concentrations the enzyme-linked immunosorbent assay technique is a low cost preferred method for tracking infliximab and anti-drug antibody levels.
One study showed that higher serum concentrations of infliximab appeared to predict sustained efficacy on that particular regimen throughout treatment however another study found no correlation between monitoring serum infliximab trough levels and disease control.
Heterogeneity was a common theme throughout the literature review with serum levels needed to control disease varying widely from patient to patient.
In general there was a trend towards higher concentrations leading to better responses but results were inconsistent.
The presence of anti-drug antibodies is associated with loss of clinical response to infliximab. Studies were conflicting with regards to the effect on serum concentrations of infliximab during treatment with immunosuppressive drugs like methotrexate and corticosteroids. While one study showed no benefit on disease activity with immunosuppressive drugs, another indicated a lower risk for developing anti-drug antibodies on suppressive therapy.
Pharmacokinetic efficacy and safety appear similar in ankylosing spondylitis patients between infliximab and a biosimilar which could lead to cost savings for patients.
Although these results are highly variable, most studies did confirm that higher trough levels of infliximab were associated with better responses. Dr. Gimenez and colleagues believe that it is necessary to collect more specific data on the relationship between infliximab levels and disease response in spondyloarthritis.
It was also determined that while switching from an innovator drug to a biosimilar in spondyloarthritis had no clinical benefit, the similar safety and efficacy may lead to cost savings.
The primary finding of this investigation was that studies to date compile different clinical data, which are difficult to compare due to different dosage regimens and activity indices, which makes comparing them very difficult.
Therapeutic drug monitoring with serum concentration and anti-drug antibody detection may develop into a useful tool that permits individualization of anti-tumor necrosis factor therapy in the future. These data, while not lending any definitive conclusions, show that spondyloarthritis patients have very different responses to the same therapy. This sheds light on the importance of individualized treatment plans based on established and validated measures.
While these conclusions are less than satisfying, they highlight the need for agreement between researchers with regards to developing protocols able to definitively conclude whether therapeutic drug monitoring can help in making pharmacologic dosing decision in spondyloarthritis on par with other rheumatologic inflammatory diseases.
Source: Maria Jose Fobelo Lozano, Reyes Serrano Gimenez, Susana Sanchez Fidalgo. "Therapeutic drug monitoring of infliximab in spondyloarthritis. A review of the literature." Br J Clin Pharmacol. 2019;1–16. DOI: 10.1111/bcp.14062