In adults with inflammatory bowel disease (IBD), basing maintenance infliximab dosing on serum trough concentrations instead of clinical response led to significantly fewer flares and cut costs by 28%, researchers reported in the June issue of Gastroenterology (2015 Feb. 24[doi:10.1053/j.gastro.2015.02.031]).
“Our results indicate that adaptive dosing of infliximab based on exposure results in better short-term clinical outcomes and that by maintaining this adequate exposure, the risk for loss of response can be reduced,” said Dr. Niels Vande Casteele at the University of Leuven, Belgium, and his associates. “A similar approach of dosing of tumor necrosis factor antagonists based on exposure could prove to be superior in other chronic inflammatory diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis.”
Infliximab is a tumor necrosis factor (TNF) antagonist with proven efficacy in Crohn’s disease (CD) and ulcerative colitis. But up to 60% of patients who initially respond to infliximab later stop responding and need either a dose increase or a switch to another TNF antagonist, the investigators noted. Loss of response has been tied to increased drug clearance, while serum trough concentrations have been found to help predict clinical response, remission, and mucosal healing, they added (Gastroenterology).
The study included 263 adults with moderate to severe CD or ulcerative colitis who had initially responded to infliximab therapy. The researchers first optimized maintenance infliximab dosing based on a target trough concentration of 3-7 mcL/mL, and then randomized patients to further dosing based on either clinical response or the same target concentration. The study’s primary endpoint was clinical and biological remission at 1 year. The investigators defined clinical remission as a Harvey-Bradshaw index of no more than 4 for CD, or a partial Mayo score no higher than 2 with no individual subscore above 1 for ulcerative colitis. They defined biological remission as a C-reactive protein concentration no higher than 5 mg/L.
One year after dose optimization, 69% of patients who were dosed based on trough concentrations had achieved clinical and biochemical remission, compared with 66% of the patients dosed based on clinical response (P =.686), the researchers reported. However, flares occurred in only 7% of the concentration-based dosing group, compared with 17% of the clinical dosing group (P =.018), they said. Furthermore, reducing the infliximab dose for patients whose trough concentrations were above 7 mcL/mL led to a cost savings of 28% and did not increase risk of flares. In patients with Crohn’s disease, upping the dose for underdosed patients improved remission rates from 65% to 88% (P =.02), and significantly lowered the median CRP level from 4.3 to 3.2 mg/L (P < .001), the investigators also reported. They did not observe these trends among patients with ulcerative colitis.
Based on the results, the researchers recommended longer-term randomized trials with early dose optimization and drug monitoring during induction or shortly afterward. “Because of the longer turnaround time of current assays for therapeutic drug monitoring, a change in treatment was only possible for the next administration of drug, thereby delaying the implementation of the algorithm,” they noted. The study also did not use other objective measures of disease activity, such as centrally read endoscopy or fecal calprotectin levels, they added.
The Research Foundation–Flanders in Belgium partially supported the research. Dr. Casteele reported consulting and speaker fees from MSD, Janssen Biologics, UCB, and AbbVie. Five coauthors reported relationships with numerous pharmaceutical companies, and the other four reported no relevant conflicts of interest.