Infliximab bests cyclophosphamide as first-line treatment of severe Behçet’s syndrome
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Key takeaways:
- Week-22 remission rates were 81% among patients using infliximab and 56% in those on cyclophosphamide.
- Mild to moderate adverse events impacted 29.6% and 64% of patients, respectively.
Patients with severe Behçet’s syndrome who received infliximab demonstrated better odds of achieving complete response at 22 weeks compared with those who used cyclophosphamide, according to head-to-head data published in NEJM Evidence.
“Cyclophosphamide and glucocorticoids have long been the standard remission-induction therapy for severe Behçet’s syndrome,” David Saadoun, MD, PhD, of the Pitié-Salpêtrière University Hospital, in Paris, and colleagues wrote. “... However, disease flares requiring repeated treatment courses may lead to high cumulative doses of both drugs over time. The short- and long-term adverse events (AEs) of cyclophosphamide use in Behçet’s syndrome are substantial and add to the known side effects of glucocorticoids, further increasing overall rates of treatment-related morbidity.
“TNF inhibitors have been successful in eliciting high response rates in severe and refractory Behçet’s syndrome in retrospective series and have also been associated with decreased blindness in Behçet’s syndrome uveitis,” they added. “These data suggest infliximab may be a promising agent for the treatment of severe Behçet’s syndrome and raise the question of whether it should be used earlier in Behçet’s syndrome management.”
To compare cyclophosphamide vs. infliximab (Remicade, Janssen) as first-line therapies in severe Behçet’s syndrome, Saadoun and colleagues conducted a phase 2, open-label, randomized controlled trial across 21 centers in France between May 2018 and April 2021. The study included 52 patients with severe Behçet’s syndrome (median age, 39.4 years), 71% of whom demonstrated vascular Behçet’s while 29% had neuro-Behçet’s.
With a background therapy of 1 mg/kg of daily oral prednisone, 25 patients were randomly assigned to receive 5 mg/kg infliximab at weeks 0, 2, 6, 12 and 18, while 27 were assigned to 0.7 g/m2 of cyclophosphamide at weeks 0, 4, 8, 12, 16 and 20 (maximal dose was set at 1.2 g per infusion). The primary outcome was complete response at week 22, which was defined as resolution of all baseline clinical manifestations of vascular or neuro-Behçet’s syndrome, normalization of C-reactive protein levels, and radiological remission while on 0.1 mg/kg of prednisone or less per day.
According to the researchers, 81% of patients treated with infliximab achieved complete response at week 22 vs. 56% of those who received cyclophosphamide, representing an estimated difference of 29.8 percentage points (95% CI, 6.6-51.7). Using Bayesian inference, the posterior probability that at least 70% of those treated would meet the primary outcome was found to be 97.4% for infliximab and 6% for cyclophosphamide, the researchers wrote.
Meanwhile, mild to moderate adverse events — mainly infections — impacted 29.6% of patients in the infliximab group (n = 8) and 64% of patients in the cyclophosphamide group (n = 16). Serious adverse events affected 15% and 12%, respectively.
“For decades, cyclophosphamide has been a cornerstone of treatment for severe Behçet’s syndrome,” Saadoun and colleagues wrote. “However, its superiority over surgery or other immunosuppressant treatments in vascular Behçet’s syndrome has mostly been documented in small retrospective studies evaluating pulmonary artery involvement.
“The findings of this phase 2 trial suggest the superior efficacy of infliximab over cyclophosphamide for induction of remission in patients with severe Behçet’s syndrome,” they added.
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