Long-term efficacy of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in two patients with systemic JIA and recurrent episodes of macrophage activation syndrome.

introductionSystemic JIA (sJIA), a multifaceted autoinflammatory disorder, can be complicated by life-threatening conditions such as macrophage activation syndrome (MAS) and interstitial lung disease. The management of these conditions presents a therapeutic challenge, underscoring the need for innovative treatment approaches.

objectivesTo report the possible role of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in the treatment of multi-drug-resistant sJIA.

methodsWe report two patients affected by sJIA with severe and refractory MAS and high serum IL-18 levels, responding to dual blockade of IL-1β and IL-18.

resultsThe first patient is a 20-year-old man, presenting a severe MAS complicated by thrombotic microangiopathy, following SARS-CoV-2 infection. He was treated with MAS825, with quick improvement. Eighteen months later, the patient is still undergoing biweekly treatment with MAS825, associated with MTX, ciclosporin and low-dose glucocorticoids, maintaining good control over the systemic features of the disease. The second patient, a 10-year-old girl, presented a severe MAS case, complicated by posterior reversible encephalopathy syndrome, following an otomastoiditis. The MAS was not fully controlled despite treatment with i.v. high-dose glucocorticoids, anakinra and ciclosporin. She began biweekly MAS825, which led to a prompt amelioration of MAS parameters. After 10 months, the patient continues to receive MAS825 and is in complete remission.

conclusionIn light of the pivotal role of IL-1β and IL-18 in sJIA, MAS and interstitial lung disease, MAS825 might represent a possible valid and safe option in the treatment of drug-resistant sJIA, especially in the presence of high serum IL-18 levels.