Anakinra treatment in drug-resistant Behcet’s disease: a case series

Abstract

The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 ± 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 ± 13.88 years and their overall disease duration was 9.55 ± 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 ± 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 ± 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.

Etiology, Immunopathogenesis and Biomarkers in Behçet’s disease

“…A proof-of-concept study by Güll et al strongly implicated IL1β and BD with significant improvement seen especially in patients with uveitis treated with IL1β-regulating antibody [47]. Recently Tugal-Tutkun et al demonstrated rapid control of uveitis in BD patients without the need for high-dose corticosteroid in a prospective, open-label, randomized phase II trial [48] supporting several other previous studies of the proven efficacy of IL1β to induce stable clinical remission among BD patients [49][50][51][52].…”

“…Evidence from the GWASs further implicated several cytokines underlying the pathogenesis of BD [17,18,[22][23][24][25][26]. Moreover, the successful use of various anti-cytokine therapies in BD patients provides additional evidence that cytokines play a crucial role in its pathogenesis [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. These overall observations highlight the fundamental role of cytokines as key players in the pathogenesis of BD.…”

Role of Interleukin 1 in the Development of Human Diseases

“…Недавно было обнару-жено увеличение экспрессии P2X7-рецепторов на моно-цитах пациентов, что способствует увеличению высвобо-ждения ИЛ1β из этих клеток [134]. В ряде исследований продемонстрирована высокая эффективность анакинры [135][136][137][138][139][140], канакинумаба [141,142] и гевокизумаба [143] у пациентов с болезнью Бехчета. Особые надежды возла-гают на гевокизумаб, лечение которым приводит к быст-рой положительной динамике увеита и симптомов пора-жения ЦНС.…”

Immunotherapies for Neurological Manifestations in the Context of Systemic Autoimmunity

“…Thus, official EULAR recommendations propose their use for refractory cases (grade 3C and 3D) [150]. Additionally, recently published small case series of patients with BD treated with tocilizumab and anakinra also include some patients with neuro-BD, and the results were encouraging [19,158].…”