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There was no differences in serious adverse event rates between patients treated with the combination therapy and patients who withdrew from infliximab or immunosuppressant therapy.
New research suggests against withdrawing from infliximab for patients with Crohn’s disease.
A team, led by Edouard Louis, MD, Department of Gastroenterology, University Hospital CHU of Liège, compared the relapse rate and the time spent in remission over 2 years between patients with Crohn’s disease treated with the standard combination therapy and patients who stop either the infliximab or immunosuppressant portion of the therapy.
The current standard treatment for patients with Crohn’s disease is infliximab and immunosuppressants. However, this is leading to concerns on the long-term viability of the treatment and whether treatment descalation is necessary.
In the multicenter, open-label, randomized, controlled trial, the investigators examined patients at 64 hospitals in 7 countries in Europe and Australia. Each participant was in steroid-free clinical remission for more than 6 months and on the combination therapy for at least 8 months. The participants were assigned to either continue the combination therapy, discontinue infliximab, or discontinue immunosuppressant therapy.
They were randomized according to disease duration before the start of the first anti-tumor necrosis factor (anti-TNF) therapy,failure of immunosuppressant therapy before the start of infliximab, and the presence of ulcers at baseline endoscopy. Treatment was optimized or resumed in cases of relapse for all 3 groups.
The investigators sought coprimary endpoints of the relapse rate and the time in remission over 2 years.
The team screened 254 patients with Crohn’s disease between Nov. 2m 2015 and April 24, 2019, 207 of which were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group).
The results show 39 patients overall had a relapse, 12% (n = 8) of the combination group, 35% (n = 25) of the infliximab withdrawal group, and 9% (n = 6) of the immunosuppressant withdrawal group. The 2 year relapse rates were 14% (95% CI, 4–23) in the combination group, 36% (95% CI, 24–47) in the infliximab withdrawal group, and 10% (95% CI, 2–18) in the immunosuppressant withdrawal group (HR, 3.45; 95% CI, 1.56–7.69; P = 0.003, for infliximab withdrawal vs combination, and HR, 4.76; 95% CI, 1.92–11.11; P = 0.0004, for infliximab withdrawal vs immunosuppressant withdrawal).
For the 28 patients who had a relapse, approximately 66% were in the immunosuppressant withdrawal group, while 33% were in the infliximab withdrawal group. The results also show the mean time spent in remission over 2 years for the patient population in the combination group was 698 days (95% CI, 668–727), compared to 684 days (95% CI, 651–717) in the infliximab withdrawal group, and 706 days (95% CI, 682–730) in the immunosuppressant withdrawal group.
There was also a difference in restricted mean survival time in remission. This was -14 days (95% CI, -56 to 27) between the infliximab withdrawal group and the combination group and -22 days (95% CI, -62 to 16) between the infliximab withdrawal group and the immunosuppressant withdrawal group.
For safety, there were 31 serious adverse events identified in 20 patients. There was no difference in frequency between the 3 groups.
The specific serious adverse events were infections and Crohn’s disease exacerbation.
“In patients with Crohn's disease in sustained steroid-free remission under combination therapy with infliximab and immunosuppressant therapy, withdrawal of infliximab should only be considered after careful assessment of risks and benefits for each patient, whereas withdrawal of immunosuppressant therapy could generally represent a preferable strategy when considering treatment de-escalation,” the authors wrote.
The study, “Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicenter, open-label, randomized controlled trial,” was published online in The Lancet Gastroenterology & Hepatology.