麻豆传媒

Intensified or accelerated dosing regimens with infliximab (Remicade) did not improve outcomes compared with the standard regimen in patients with steroid-refractory acute severe ulcerative colitis undergoing rescue therapy, the randomized PREDICT-UC trial showed.

In 138 adult patients randomized to a first dose of 10 mg/kg or 5 mg/kg, there was no significant difference in the proportion of those who had a clinical response by day 7 (65% vs 61%; risk ratio adjusted for thiopurine treatment history 1.06, 95% CI 0.94-1.20, P=0.32), reported Peter De Cruz, PhD, of the University of Melbourne in Australia, and colleagues in

At day 14, there was still no significant difference in the rate of clinical response among patients who received a second dose of the intensified 10 mg/kg regimen, those who received a 10 mg/kg dose after receiving a 5 mg/kg dose (accelerated group), and those who received a second 5 mg/kg dose (standard group): 74% vs 73% vs 68% (P=0.81).

There were also no significant differences in additional longer-term endpoints including clinical remission, steroid-free remission, endoscopic remission, or rates of colectomy at 3 months, De Cruz and colleagues noted.

"Infliximab dose optimization through intensification and interval shortening is increasingly used to treat in the outpatient setting; however, no conclusive evidence has shown that such optimization improves clinical response or colectomy-free survival in ASUC [acute severe ulcerative colitis]," they wrote.

In their study, "outcomes with intensified and accelerated induction strategies were not significantly different to those with standard induction at month 3, although post-hoc analyses suggested that clinical and biochemical remission were achieved at earlier time points than standard induction," they added.

In an , Saurabh Kedia, MD, and Vineet Ahuja, MD, of the All India Institute of Medical Sciences in New Delhi, said the study provided important data on patients with acute severe ulcerative colitis for whom dynamic decision making is crucial.

"However, for the primary and most clinically relevant outcomes of clinical response at day 7, and colectomy-free survival and clinical remission at 3 months, no significant differences were found between the treatment groups, indicating that even when patients had similar baseline severity, neither intensified nor accelerated regimens were better than the standard regimen," Kedia and Ahuja wrote.

"The PREDICT-UC study potentially signals the end of accelerated or intensified dosing strategies for infliximab as rescue therapy for ASUC, which should prompt new strategic approaches," they added.

For this open-label study conducted from July 2016 to September 2021, De Cruz and colleagues initially randomized 138 patients (median age 33, 54% men) 1:2 to a first dose of infliximab 10 mg/kg or 5 mg/kg. They subsequently randomized the 5 mg/kg group 1:1 to the standard or accelerated group. The end result was three groups of similar size for comparison.

Patients in the standard group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the accelerated group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response.

From month 3 on, maintenance therapy was selected based on treatment experience and included thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy.

The study authors noted that infliximab use during maintenance was independently associated with an increased probability of being in combined clinical and endoscopic remission at month 12 (risk ratio 1.95, 95% CI 1.29-2.93, P=0.0014).

"Although not powered for this endpoint, our data suggest that thiopurine alone is insufficient to maintain remission in a substantial proportion of patients after ASUC," the researchers wrote, "and that infliximab maintenance therapy should be considered in all patients with steroid-refractory ASUC successfully rescued with infliximab, preferably in combination with a thiopurine."

Limitations of the trial, in addition to the open-label design, included the lack of randomization in the maintenance component, which was undertaken as an observational study, the authors noted. The maintenance data, though clinically relevant, need to be interpreted with this limitation in mind, they said. The secondary randomization also likely reduced the power of subsequent comparisons, they added.

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