Maintenance infliximab more effective with therapeutic drug monitoring
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Therapeutic drug monitoring, in which serum levels are regularly checked to adjust dose and intervals, is more effective at controlling disease than standard therapy with infliximab, according to data presented at ACR Convergence 2021.
“Several observational studies have revealed a considerable inter-individual variation in serum drug levels for infliximab and other TNF inhibitors, suggesting that both over and under dosing are common,” Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital, in Oslo, Norway, told attendees at a virtual press conference. “Associations between serum drug levels and effectiveness have been shown. Therapeutic drug monitoring, or TDM, has thus been proposed as an approach to optimize efficiency as well as safety and cost effectiveness of TNF inhibitors.”
“Proactive TDM has already to some extent been adopted in clinical practice,” she added. “However, today, no clinical trial has shown that TDM improves clinical outcomes in patients treated with a TNF inhibitor, and guidelines still differ considerably with respect to recommendations for the use of proactive TDM, both across diseases and specialties.”
To examine the effectiveness of therapeutic drug monitoring during infliximab (Remicade, Janssen) maintenance therapy, Syversen and colleagues conducted the 52-week, randomized, open-label, multicenter NOR-DRUM B trial. A total of 458 participants using infliximab for a minimum of 30 weeks were assigned 1:1 to accompany their regimen with therapeutic drug monitoring or standard therapy. Among the participants, 79 had rheumatoid arthritis, 138 had spondyloarthritis, 53 had psoriatic arthritis, 81 had ulcerative colitis, 66 had Crohn’s disease and 37 had psoriasis.
Among those who received drug monitoring, infliximab doses and intervals were adjusted based on an algorithm to maintain serum levels within a prespecified range of 3 mg/L to 8 mg/L. Meanwhile, in the standard therapy group, infliximab administration was based on clinical judgement. The primary outcome was sustained disease control without worsening. The researchers defined disease worsening based on specific composite scores, or a consensus on disease worsening between investigator and patient leading to major change in treatment.
According to the researchers, 73.6% of participants who received drug monitoring achieved the primary outcome during the 52-week follow-up, compared with 55.9% of those in the standard therapy group, with an estimated adjusted difference of –17.6% (95% CI, –26.2 to –9). The results were consistent in the sensitivity analyses. The two groups were balanced in terms of baseline characteristics, the researchers wrote. There were no significant differences between the group regarding the secondary endpoints, which compared disease activity and patient reported outcomes at week 52.
The mean infliximab dose during the trial was 4.8 mg/kg in both groups. In all, 9.2% of patients in the monitoring group developed clinically significant levels of anti-drug antibodies, compared with 15 in the standard therapy group. The researchers reported adverse events in 60% and 63% of participants in the monitoring and standard therapy groups, respectively.
“We believe that these results support implementation of proactive TDM during maintenance therapy with infliximab,” Syversen said.
“Such an implementation of proactive TDM as a general strategy in all patients on infliximab will, of course, require feasible testing, available at a low cost, as we have in Norway, for instance, and also education for health care providers,” she added. “Still, maintenance therapy usually lasts for several years and preventing disease worsening and its potential impact on quality-of-life long-term outcomes can make a great difference to a large number of patients with inflammatory joint diseases.”
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Syversen WS. Abstract 1946. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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