CHICAGO — Patients with Crohn’s disease who have high serum concentrations of Remicade may not see additional clinical benefits from combination therapy with azathioprine, according to a post hoc analysis of the SONIC trial presented during a session focused on therapeutic drug monitoring in IBD at Digestive Disease Week.
The data suggest that the benefit of combination therapy “was primarily driven by [Remicade (infliximab, Janssen)] concentration rather than the synergy between azathioprine [and infliximab],” Stephen B. Hanauer, MD, professor of medicine at Northwestern University Feinberg School of Medicine, Chicago, said during his presentation.
Stephen B. Hanauer
To further study the benefit of combination therapy in patients with different infliximab concentrations, Hanauer and colleagues re-analyzed data from the SONIC trial. In that trial, researchers randomly assigned patients with moderate-to-severe Crohn’s disease — who were naive to both immunosuppressants and biologics —to receive azathioprine, infliximab, or combination therapy with both agents.
This trial “demonstrated that there was about a 13% benefit to the combination therapy,” Hanauer told Healio Gastroenterology. “Also in the main publication it was noted that patients who received combination therapy ... had higher infliximab levels and lower levels of antibodies to infliximab. So in our re-analysis, we asked the question, ‘What is the benefit from combination therapy? Is it synergy in that azathioprine and infliximab are working together via different mechanisms, or is it simply that azathioprine raises the infliximab blood levels?”
The investigators identified 206 patients whose serum infliximab concentrations (SIC) were measured at week 30 of the trial, and analyzed them based on treatment arm, SIC quartiles and efficacy outcomes.
The analysis confirmed that higher proportions of patients who received combination therapy had higher trough infliximab levels. However, among patients with similar SIC ranges in different treatment arms, clinical efficacy (defined as corticosteroid-free remission at week 26) was not consistently improved with the addition of azathioprine.
Though the researchers observed some improvements in mucosal healing with combination therapy, this was only notable, but not statistically significant, in the two lowest SIC quartiles.
Further, investigators observed antidrug antibodies only in the lowest SIC quartile, within which more patients on monotherapy (35.9%) had antidrug antibodies compared with those on combination therapy (8.3%).
The findings suggest that azathioprine comedication may not be needed in the presence of higher SIC levels in patients with Crohn’s disease, although Hanauer noted in his presentation that without azathioprine, it is possible that patients could develop anti-infliximab antibodies as a result of the lower SIC levels, which could reduce efficacy.
“We are looking for additional clues and tools with therapeutic drug monitoring so that we can optimize even the patients who would have been in the lowest quartile and make certain from the onset that their levels are sufficient to induce the appropriate endpoints,” Hanauer concluded in his presentation. – by Adam Leitenberger
Colombel JF, et al. Abstract #134. Presented at: Digestive Disease Week; May 6-9, 2017; Chicago.
Disclosures: Hanauer reports financial relationships with AbbVie, Janssen, Takeda, Pfizer, Celgene, Shire, Salix, Hospira, Merck, Boehringer Ingelheim, Amgen, Samsung Bioepis, Arena, Lilly, Seres Health, Tigenex, VHsquared and UCB.