Successful canakinumab treatment identifies IL-1β as a pivotal mediator in Schnitzler syndrome

Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome

“…To date, anakinra (recombinant IL-1 receptor antagonist) has been used most often for the treatment of patients with Schnitzler syndrome but canakinumab, monoclonal antibodies against IL-1b, and rilonacept (an IL-1 Trap) have also been reported to induce complete disease responses. [8][9][10] Despite substantial clinical similarities between CAPS and Schnitzler syndrome, the pathogenic mechanisms underlying the latter syndrome remain obscure, in particular, the interplay between the monoclonal protein and increased IL-1b production. Thus far, no genetic influence has been identified in Schnitzler syndrome, although speculation about the contribution of genetic factors has been fueled by the finding of the common NLRP3 p.V198M variant in 2 patients with the classical-type Schnitzler syndrome, 11,12 and the detection of somatic NLRP3 mosaicism in 2 patients with the variant-type Schnitzler syndrome.…”

Administration of the Interleukin-1 Inhibitor Canakinumab in Children with Autoinflammatory Diseases and Systemic Juvenile Arthritis: the Report for Case Series

“…Проводятся многоцентровые исследования, и нака-пливается опыт применения канакинумаба и при других аутовоспалительных заболеваниях (HIDS/MKD, семейная средиземноморская лихорадка, резистентная к тради-ционному лечению колхицином, синдром Шнитцлера) [29,30].…”

Schnitzler syndrome: clinical features and histopathology

“…[23][24][25][26] Although serum IL-1 levels are normal in patients with Schnitzler syndrome, isolated mononuclear cells from such patients secrete large amounts of IL-1 and IL-6 in response to lipopolysaccharide stimulation. 25,27 In addition, the rapid, and often complete, response to therapy directed against IL-1 with anakinra, 5 canakinumab, 28 and rilonacept 29 clearly shows the central role that IL-1 plays in at least the manifestations of the disease. Although IL-1 is produced by monocytes and neutrophils, it has protean manifestations, including stimulation of chondrocytes, which may explain the joint symptoms that often plague these patients.…”

“…The US Food and Drug Administration rates anakinra as "B" during pregnancy, which generally means that although there is no good evidence of risk, any studies that are available provide little information about the risks in human pregnancy associated with this medication. Some patients have also responded to therapy with canakinumab (anti-IL-1β) 28 or the IL-1 Trap (rilonacept), 29 although the experience with the latter agents is much more limited. Experts also recommend consideration of the anti-IL-6 receptor monoclonal antibody tocilizumab in patients who fail therapy with the other agents, although evidence of benefit is also limited.…”