In this issue of the Journal of Clinical Gastroenterology Jiang and colleagues report a randomized, placebo controlled, double-blind study evaluating the efficacy of low-dose (3.5 mg/kg) infliximab for induction and maintenance treatment in Chinese patients with active moderate-severe ulcerative colitis (UC).1 The experimental design was modeled after the ACT 2 trial2 but included both a 5 mg/kg (standard-dose) group and a 3.5 mg/kg (low-dose) group, as well as a placebo control arm. 123 UC patients were distributed equally among the cohorts. The authors report similar rates of clinical response at week 8 (73% vs 78%) and at week 30 (51% vs 53%) in both the low and standard infliximab dose treatment arms respectively. Placebo rates were 37% at week 8 and 27% at week 30 with response defined as a ≥3 point drop in the Mayo score. Differences in mucosal healing were also significantly greater in both infliximab groups. The study was not adequately powered to detect a difference between the low- and standard-dose groups, but the authors limit their conclusions to state that both doses are more effective than placebo. The ACT 1 and 2 studies demonstrated a 61–64% clinical response at week 8 and 31–41% clinical remission at week 30 in UC patients receiving 5mg/kg of Infliximab. These studies did not identify a statistically significant clinical benefit to using 10 mg/kg over 5 mg/kg dosing as a starting dose, although 10 mg/kg over 5 mg/kg dosing resulted in higher serum infliximab levels.2, 3 A lowest-effective dose was not demonstrated in the ACT studies. Jiang et al used this as impetus in designing their study testing a dose lower than 5 mg/kg. A similar “low-dose” infliximab strategy was also recently evaluated and confirmed in psoriatic arthritis, where a recent observational cohort study of 462 patients showed that low dose infliximab (3 mg/kg) resulted in similar clinical response and drug levels following 12 months treatment.4 If the efficacy and long-term outcomes of this study’s findings are confirmed, this low-dose strategy could have important health care economic implications. While biosimilars may eventually change this, a 100 mg vial of infliximab costs ~$900 in the United States.5 At this cost, an 80 kg person receiving 5mg/kg generates a drug cost of almost $47,000 in the first year of treatment. In contrast, that same individual receiving the low-dose (3.5mg/kg) infliximab strategy would require 280mg per infusion corresponding to less than $33,000 for the first year. This is a $14,000 per first year, per patient savings! The economic benefit is potentially staggering considering that tens of thousands of UC patients receive Infliximab for multiple years. This low-dose is probably not for all UC patients. Jiang and colleagues enrolled patients with an average Mayo score of 6.0 compared to 8.4 used in ACT 1.1, 2 A Mayo score of 6 is at the border between mild and moderate ulcerative colitis. Patients with severe UC are often treated with higher doses of Infliximab. In severe colitis, infliximab may be lost through the leaky gut barrier,6 requiring higher infusion dose to maintain adequate serum levels. Additionally, infliximab systemic disposition is influenced by body weight, serum albumin levels (which are often decreased in severe UC), and formation of antibodies to Infliximab (ATI).7 Serum concentration of Infliximab is associated with efficacy in patients with moderate-to-severe ulcerative colitis.3 Unfortunately, Jiang et al did not measure or report drug levels. However, they did evaluate for ATIs and UC patients with 3.5mg/Kg vs 5 mg/Kg did not show any difference in formation of ATI (5 %) at 30 weeks and compared similarly to ACT 1 and 2 studies (6%).2 How might this study influence our current practice? Based on this single center study, we are probably not yet ready to implement this low-dose strategy, at least in the US. However, we do propose that the results of this study support consideration of a few practical management tips for use of infliximab in UC patients. First, infliximab does not need to be “maxed-out” or given at high dose in all patients, especially in those with moderate disease severity or limited extent. Second, these results further validate an approach where patients initially receive standard dose Infliximab that is escalated as needed based on clinical and endoscopic response.8, 9 Third, for patients maintained on Infliximab who are in long-term “deep” remission, consideration should be given to reducing or spacing out their dose, especially if they are on a concomitant immunomodulator. In conclusion, these results suggest that a low-dose infliximab induction strategy may be both an effective and cost-advantageous option in patients with moderately active ulcerative colitis. Confirmative studies are warranted in this same population before management is likely to change. Larger, confirmative studies are needed and should also include data on long-term outcomes. Given the potential cost savings, perhaps governmental medical payers (CMS) or commercial health insurers would be interested in sponsoring such a trial.