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IBD patients show better outcomes with proactive vs. reactive drug monitoring
Patients with inflammatory bowel disease showed better long-term clinical outcomes when they received proactive monitoring of Remicade serum levels to optimize maintenance therapy before losing response to the drug, rather than reactive monitoring after loss of response, according to new research published in Clinical Gastroenterology and Hepatology.
This research “could set the stage for a change in the standard clinical approach to IBD,” according to a press release.
“We showed significant benefits of proactive therapeutic drug monitoring (TDM) when compared to reactive TDM,” Adam S. Cheifetz, MD, director of the Center for Inflammatory Bowel Disease at Beth Israel Deaconess Medical Center, and associate professor of medicine at Harvard Medical School, told Healio Gastroenterology and Liver Disease.
In collaboration with colleagues from the University of Pennsylvania, including Mark T. Osterman, MD, associate professor of medicine at the Perelman School of Medicine, the research team reviewed long-term outcomes data on 264 consecutive IBD patients who received maintenance Remicade (infliximab, Janssen) from September 2006 to January 2015. Sixty-three percent had Crohn’s disease and median follow-up was 2.4 years. They defined patients as having undergone either proactive (49%) or reactive (51%) TDM depending on their first measurement of infliximab concentrations or antibodies to infliximab.
The study showed proactive monitoring “was associated with significantly less treatment failure, IBD-related hospitalizations and surgeries, antibodies to infliximab, and serious infusion reactions,” Cheifetz said.
Thirteen percent of those who received proactive TDM showed treatment failure compared with 66% of those who received reactive TDM. Further, 6% vs. 19% required surgery, 7% vs. 25% were hospitalized, 2% vs. 9% had serious infusion reactions, and 9% vs. 28% showed antibodies to infliximab (most of whom already had detectable antibodies at the start of TDM).
Hazard ratios showing independent associations with proactive vs. reactive TDM were as follows:
- treatment failure (HR = 0.16; 95% CI, 0.09-0.27);
- surgery (HR = 0.3; 95% CI, 0.11-0.8);
- hospitalization (HR = 0.16; 95% CI, 0.07-0.33);
- antibodies to infliximab (HR = 0.25; 95% CI, 0.07-0.84); and
- serious infusion reactions (HR = 0.17; 95% CI, 0.04-0.78).
While both patients with ulcerative colitis and Crohn’s disease “benefited greatly from proactive TDM when compared to reactive TDM,” Cheifetz noted that “the bigger split of Kaplan Meier curves in UC compared to Crohn’s disease is due to the higher rate of treatment failure in UC.” He added that “proactive TDM may actually be more important in UC where disease burden is often higher than in Crohn’s disease, although both clearly did better with proactive TDM.”
Given these findings, study investigators recommended that physicians who include TDM in the management of their IBD patients should consider doing so proactively to optimize maintenance infliximab before loss of response, but Cheifetz acknowledged there are several obstacles.
“Though it is commonplace to do proactive TDM with dosing to a therapeutic window in other situations and with other medications such as cyclosporine for UC, tacrolimus to prevent organ rejection post-transplant, and antibiotics (vancomycin and gentamycin) for sepsis, it has not caught on for treatment of IBD with anti-TNF,” he said. “I think the greatest barrier to adoption of proactive (and even reactive) TDM is the potential out-of-pocket cost to the patient for one of the most commonly used commercial assays. There is likely also a lack of knowledge about the benefits of proactive TDM among gastroenterologists, and the lack of a clearly defined therapeutic window.”
Further research on proactive TDM is needed to fill what the AGA called a critical knowledge gap in its recent guideline on TDM in IBD.
The next big step is to develop a prospective study on proactive TDM, and because “proactive TDM is very important with all biologics due to their potential immunogenicity,” Cheifetz said he and his team are also currently analyzing its potential benefits in IBD patients on Humira (adalimumab, AbbVie). – by Adam Leitenberger
Disclosures: Cheifetz reports consulting for AbbVie, Janssen, UCB, Takeda, Prometheus and Pfizer, and Osterman reports consulting for Janssen, AbbVie, UCB Takeda, Pfizer and Lycera, and received research grant support from UCB. Please see the full study for a list of all other authors’ relevant financial disclosures.