Background: Loss of response (LOR) occurs in 60% of Crohn's disease (CD) patients by week 54 of receiving infliximab (IFX) at 5 mg/kg/8 week. Dose escalation and interval shortening are common approaches to treatment of CD patients with LOR to IFX. However, data are still lacking on the appropriate time to evaluate the efficacy of IFX dose escalation, and few studies have investigated long-term efficacy or predictors of response. The aim of this study was to investigate the long-term efficacy, safety, and appropriate time to evaluate the efficacy of double-dose infliximab therapy in active luminal CD.
Methods: We retrospectively reviewed the outcome of consecutive CD patients treated with infliximab dose doubling (to 10 mg/kg) for LOR between 2011 and 2016 in a single tertiary centre. Patients whose IFX infusion intervals had been shortened, whose dose had been escalated to a dose other than 10 mg/kg/8 week, or reduced to less than 10mg/kg during the follow-up period were excluded. Clinical response and remission were assessed, Cox regression analysis was performed to identify predictors of clinical response, and the cumulative rate of intestinal resection-free survival was calculated using Kaplan–Meier analysis. All adverse events were recorded.
Results: Fifty-five patients with active luminal CD were included. The median CDAI score was 255 at initiation of IFX dose-doubling. After IFX dose doubling, clinical response rates were 44% at week 8, 62% at week 32, and 44% at week 48, respectively. Clinical response was associated with haemoglobin level (p=0.067) and serum albumin level (p=0.047) at initiation of IFX dose-doubling. The duration of intestinal resection-free survival was 95% at 1 year, and 83% at 3 years. The long-term intestinal resection-free survival was associated with efficacy at Week 8 (100% of the 8-week responders were free of intestinal resection at 3 years vs 51% of 8-week non-responders, p=0.0051). Adverse events were reported in four patients (7.3%); one patient had to discontinue IFX therapy because of an anaphylactic infusion reaction, and other patient was diagnosed with rectal cancer.
Conclusions: IFX dose doubling seems to be well-tolerated and may be effective in inducing clinical remission in patients with luminal CD with LOR to IFX. Appropriate time to evaluate the efficacy of double-dose infliximab therapy assumed to be 8–32 weeks. Response at 8-weeks was predictive of long-term prognosis of double-dose infliximab therapy.