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
Roberta Caorsi, Arinna Bertoni, Caterina Matucci‐Cerinic, Valentina Natoli, Serena Palmeri, Silvia Rosina, Federica Penco, Clara Malattia, Alessandro Consolaro, Stefania Viola, Riccardo Papa, Anna Corcione, Stefano Volpi, Angelo Ravelli, Marco Gattorno
Abstract
INTRODUCTION: Systemic 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. OBJECTIVES: To report the possible role of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in the treatment of multi-drug-resistant sJIA. METHODS: We 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. RESULTS: The 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. CONCLUSION: In 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.