Induction Therapy With Anti-TNFα vs Cyclophosphamide in Severe Behçet Disease
Status:
Not yet recruiting
Trial end date:
2022-01-01
Target enrollment:
Participant gender:
Summary
Behçet's disease (BD) is a systemic vasculitis of arterial and venous vessels of any size,
involving young patients (from 15 to 45 years). BD significantly increases morbidity and
mortality. Therapeutic management of BD depends on the clinical presentation and organ
involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments
are often sufficient for mucocutaneous and joint involvement, more aggressive approach with
immunosuppressive agents is warranted for severe manifestations. Early recognition and
vigorous use of immunosuppressives with high dose steroids have changed the prognosis of
patients with severe BD. BD is a severe systemic vasculitis leading to blindness in up to 20%
at 4 years and a 5-year mortality rate of 15% in patients with major vessel or neurological
involvement. Cyclophosphamide has been used for life-threatening BD for 40 years. However,
the outcome of severe complications of BD is poor. The European League Against Rheumatism
(EULAR) recommendation for the management of BD advocated cyclophosphamide plus
glucocorticoids for life-threatening manifestations (i.e neurological and/or major vessel
involvement). TNFa antagonists have been used with success in severe and/or resistant cases.
In addition, the incidence of blindness in BD has been dramatically reduced in the recent
years with the use of anti-TNF. However, there is no firm evidence or randomized controlled
trials directly addressing the best induction immunosuppressive therapy in severe BD
manifestations. The investigators therefore aimed to assess the best induction therapy in
severe and difficult to treat BD patients. The investigators hypothesize that up to 70% of
the patients with life-threatening manifestations of BD receiving these compounds [anti-TNFa
or cyclophosphamide] will achieve a complete remission of BD at 6 months and with less than
0.1 mg/kg/day of prednisone.
ITAC, is the first randomized prospective, head to head study, comparing infliximab, to
cyclophosphamide in severe manifestations of BD. There is no firm evidence or randomized
controlled trials directly addressing the best induction immunosuppressive therapy in severe
BD. Cyclophosphamide failed to demonstrate sustainable remission over 70 % of life
threatening BD cases. There is little published information on use of immunosuppressants
other than cyclophosphamide for severe BD. TNFa antagonists have been used with success in
severe and/or resistant cases. TNFa expression correlates with BD activity and other
immunological data provide a strong rationale for targeting BD with biologics. Despite a
strong rationale, these compounds are not yet approved in BD, which guarantees the innovative
nature of this study that aims selecting or dropping any arm when evidence of efficacy
already exists.