Behçet’s disease is an inflammation of blood vessels, of all types (arteries and veins) and of all sizes. “In some ways, it’s an auto-inflammatory disease and in others, it’s vasculitis,” explains the Professor Patrice Cacoubhead of the department of internal medicine and clinical immunology at Pitié-Salpêtrière (AP-HP).
The causes of the disease are not known, but it affects specific populations, coming from the historic “Silk Road”: Mediterranean basin, Middle East and Far East.
“Certain haplotypes such as HLA B51 are six times more likely to develop Beçhet’s disease,” underlines Professor Cacoub. “It is now believed that on this genetic basis, certain antigenic attackers cause activation of CD4 T lymphocytes, causing an inflammatory cascade which can lead to ophthalmic damage (uveitis), oral and genital ulcers, joint pain or, in the most severe forms, cerebral and vascular damage that can be life-threatening or functional,” he explains. The disease progresses in flare-ups, with periods of remission.
Eye damage that can lead to blindness
The most serious forms may include intracerebral venous thrombosis, deep venous thrombosis affecting the venae cavae, or even arterial thrombosis. Eye damage can also be very severe and lead to blindness, particularly when the posterior segment of the eye is affected.
Current treatments for the disease depend on its form. “If the damage is cutaneous or mucosal, we treat with colchicine or apremilast. In the event of eye damage, corticosteroids are combined with an immunosuppressant, often infliximab.
And in the most complicated forms, with vascular, arterial or neurological damage, corticosteroids are also prescribed in combination with an immunosuppressant, left to the doctor’s choice: cyclophosphamide or infliximab,” explains Professor Cacoub. However, no randomized controlled study has yet been conducted to determine the effectiveness of these medications.
This is why Professor Cacoub and his team decided to launch the ITAC trial [1]the first prospective, randomized, controlled trial to show the effectiveness of these drugs.
Between May 2018 and April 2021, 52 patients suffering from severe Behçet’s disease were included in 21 centers across France. The patients were on average 40 years old and two thirds of them had severe vascular disease, half of which affected the arteries and half of which affected the veins. The remaining 30% suffered from central neurological damage. “Most were already receiving corticosteroids and immunosuppressive treatment,” specifies the doctor.
81% response for patients on infliximab
Patients were randomly divided into two groups, one receiving cyclophosphamide (25 patients) and the other receiving infliximab (27 patients). Infliximab was injected at a rate of 5 mg/kg intravenously, on average every four weeks. Cyclophosphamide was injected at a rate of 0.7g/m² per month intravenously. At the same time, all patients received corticosteroid therapy with decreasing doses: from 1 mg/kg/day to less than 0.1 mg/kg/day at week 22.
-The primary endpoint was complete response (clinical, biological and radiological remission) at week 22.
“We demonstrated such a response for 81% of patients receiving infliximab, compared to 56% of patients receiving cyclophosphamide,” indicates Professor Cacoub.
Secondary endpoints, including vascular or neurological response, were more favorable for infliximab. Tolerance was also better with this treatment (30% side effects, compared to 64% in the cyclophosphamide group). Furthermore, four times fewer relapses were observed in the infliximab group (16% vs 4%).
“Thanks to Bayesian statistics, we can calculate the posterior probability for a patient to achieve a complete response at week 22. We obtained a result of 97.4% for infliximab, compared to 6% for cyclophosphamide,” emphasizes Professor Cacoub.
For him, this study “made it possible to answer the unresolved question of the effectiveness of treatments and in a very clear way. This will change patient care and infliximab will replace cyclophosphamide tomorrow,” he believes.
Links of interest of experts: None
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