Although rheumatologists prescribe tumor necrosis factor inhibitors (TNFi’s) to treat several rheumatic diseases, they recognize immunogenicity influences the efficacy and safety of TNFi’s. Example: The formation of anti-drug antibodies can affect infusion reactions and cause low-serum drug levels and therapeutic failure. The induction phase is a period of high incidence of immunogenicity, and observational data suggest low drug levels in the induction phase are associated with low remission rates. Consequently, some clinicians use therapeutic drug monitoring during induction to improve remission rates.
Therapeutic drug monitoring should make it possible to optimize drug levels and provide early identification of anti-drug antibodies, improving the efficacy, safety and cost effectiveness of TNFi therapy. Some clinical guidelines even recommend the use of proactive therapeutic drug monitoring. However, therapeutic drug monitoring can be costly and time consuming.
Studies estimate that 50–90% of gastroenterologists in Europe and the U.S. use therapeutic drug monitoring to regularly assess serum levels for TNFi’s. Although less frequently used by rheumatologists, therapeutic drug monitoring is one potential strategy to help patients with rheumatic disease taking TNFi’s achieve remission. But will it work?
Effect on Remission Rates
New research demonstrates that proactive therapeutic drug monitoring does not improve clinical remission rates in patients with immune-mediated inflammatory diseases initiating treatment with the TNFi infliximab. Silje Watterdal Syversen, MD, PhD, a consultant rheumatologist and researcher at Diakonhjemmet Hospital, Oslo, Norway, and colleagues conclude their findings do not support routine use of therapeutic drug monitoring during infliximab induction. They published their results from a randomized controlled trial studying the effectiveness of therapeutic drug monitoring in a range of immune-mediated inflammatory diseases on May 4 in JAMA.1
The Norwegian Drug Monitoring trial part A (NOR-DRUM A) included 411 adult participants with an inflammatory disease—rheumatoid arthritis (RA; n=84), psoriatic arthritis (PsA; n=45), spondyloarthrtitis (SpA; n=119), ulcerative colitis (n=83), Crohn’s disease (n=58) and psoriasis (n=22)—who were initiating infliximab therapy. The investigators chose the large, diverse group of patients to reflect real-life practices. They randomized patients (1:1) in the open-label trial to receive either proactive therapeutic drug monitoring, with dose and interval adjustments based on scheduled monitoring of serum drug levels and anti-drug antibodies, or standard infliximab therapy without drug and antibody level monitoring. Patients received at least two doses of the study drug, with a recorded treatment decision for the third dose. The median serum level of infliximab was 6.9 mg/L in both groups.
Overall, the study had a high retention rate and tight adherence to the treatment algorithm. Definitions of clinical remission in each diagnosis were based on well-established measures of disease activity with predefined cutoff points. These included a Disease Activity Score in 28 Joints lower than 2.6 in patients with RA and PsA, Ankylosing Spondylitis Disease Activity Score lower than 1.3 in patients with SpA and Psoriasis Area and Severity Index of 4 or lower in patients with psoriasis.