Infliximab versus Adalimumab: Can We Choose the Right One for the Right Patients with Ulcerative Colitis?

To the Editor:

We read with great interest the article by Lee et al.¹ comparing the efficacy of infliximab and adalimumab for biologic-naïve patients with ulcerative colitis (UC). The authors emphasize the similar efficacy and long-term outcomes between these two anti-tumor necrosis factor (TNF) agents for biologic-naïve patients with moderate-to-severe UC. In their retrospective study, the authors compared various outcomes, including clinical remission and response, hospitalization, discontinuation or switching of drugs, and rescue corticosteroid use, between biologic-naïve UC patients who received infliximab (n=83) and those who received adalimumab (n=30). During the median 26 months of follow-up, the above outcomes were comparable between infliximab and adalimumab users. However, there were differences between the two groups. At baseline, the Physician Global Assessment subscore of the Mayo score was significantly better in the adalimumab group (p=0.028), and the rates of UC-related hospitalization and corticosteroid use during follow-up seemed higher in the infliximab group, but these differences were not statistically significant (p=0.085 and p=0.082, respectively). Additionally, colectomies (n=2) were performed on only patients treated with infliximab, and the rates of adverse events seemed higher in the infliximab group than in the adalimumab group, although this difference was not statistically significant. With their article, Lee et al. fill the knowledge gap on the comparative efficacy of representative anti-TNF agents, i.e., infliximab and adalimumab, for UC among biologic-naïve patients, particularly Korean patients, for whom there are limited data on this topic.

Although a head-to-head trial has not been performed to compare the efficacy of these two drugs directly, there have been several relevant observational studies conducted in Western countries. A recent study using a nationwide Danish cohort and a propensity score matching analysis reported a higher risk of hospitalization and serious infections among UC patients treated with adalimumab (n=104) than among those treated with infliximab (n=171).² Another population-based study from the United States addressing this issue showed no difference in all-cause and UC-related hospitalization between the infliximab (n=1112) and adalimumab (n=288) groups; however, adalimumab users may have had a higher risk of corticosteroid use and a lower rate of drug persistence.³ In network meta-analyses, infliximab seemed superior to adalimumab in the induction or maintenance phase of UC treatment.^4-6 These studies reported that infliximab is slightly more efficacious than adalimumab, whereas the study by Lee et al.¹ seemed to favor adalimumab over infliximab. This discrepancy among studies comparing these two drugs for UC treatment could be partly due to the different study designs, the heterogeneity of the study populations, or adalimumab being relatively underdosed in Caucasian populations whose body weights are usually higher than those of Asian patients.

Regarding the clinical applications of the authors’ findings, we would like to report some of our observations and impressions. First, as discussed by the authors, dose optimization strategies for infliximab and adalimumab have differed due to the Korean reimbursement policy during the study period. UC patients experiencing secondary loss of response have been allowed to shorten their adalimumab injection intervals to every week, whereas infliximab dose-doubling and interval shortening have not been allowed in the same setting. Although the authors performed subgroup analyses comparing the outcomes between weekly adalimumab (n=8) and biweekly adalimumab (n=22) as well as biweekly adalimumab and infliximab groups, which showed no differences in efficacy, the sample size was too small to yield a clinically meaningful conclusion on this issue. We suggest that patients who experienced secondary loss of response to standard doses of infliximab or adalimumab should be considered as showing “poor outcomes” to allow for a valid efficacy comparison between these two agents and minimize selection bias during the analyses. Second, in line with the dose optimization issue, pharmacokinetic data were not reported in the article, maybe because therapeutic monitoring for anti-TNF agents was not feasible during the study period in Korea (between 2012 and 2017). Given that checking the trough levels of anti-TNF drugs and anti-drug antibodies in the setting of secondary loss of response would be helpful for treatment planning,^7,8 future studies using pharmacokinetic data to evaluate the efficacy of anti-TNF agents in Korean inflammatory bowel disease (IBD) patients are warranted. Third, in Korea, the reimbursement policy requires an assessment of the Mayo score using sigmoidoscopy at weeks 0 and 8–10 for every patient receiving infliximab or adalimumab induction therapy for UC.⁹ Therefore, the comparison of these two drugs would have been more objective if this study had presented the data on endoscopic subscores after the infliximab and adalimumab induction regimens.

The incidence and prevalence of IBD have been rapidly increasing in recent decades, especially in Asian countries, including Korea.^10-14 Along with the increasing disease burden, the requirement of immunomodulators and anti-TNF agents for managing IBD patients has also been increasing.^15,16 Although efficacy data for anti-TNF agents in Asian IBD patients have been reported,^17-22 there has been a lack of comparative efficacy data for biologic agents used to treat IBD, especially for non-Caucasian populations. Realistically, head-to-head clinical trials comparing infliximab and adalimumab, so-called first-generation anti-TNFs, would not be feasible in the future; therefore, the real-world data garnered from studies like that conducted by Lee et al.¹ are helpful for guiding optimal therapies for IBD patients in Korea. In addition to the findings of this study, we should consider other factors, such as patients’ preferences, costs, and safety profiles, to optimize IBD care under a shared decision-making paradigm because one size does not fit all in this context. Of course, in the future, the therapeutic patterns and real-world efficacy and safety of these medications should be validated by prospective, observational cohort studies enrolling Korean patients.²³