BIOLOGIC THERAPIES IN SYSTEMIC JIA ASSOCIATED MACROPHAGE ACTIVATION SYNDROME: A SYSTEMATIC REVIEW

Background: Macrophage activation syndrome (MAS), a potentially life threating complication of systemic juvenile idiopathic arthritis(sJIA), is characterized by hypercytokinemia. Biologic therapies have been used for over a decade to manage MAS, yet evidence supporting this approach remains limited. Objectives: This systematic literature review aims to identify current and emerging treatment options for sJIA-associated MAS and describe their efficacy. Methods: According to the PRISMA guidelines, PubMed and Scopus were searched from inception to December of 2023 using the search terms: “macrophage activation syndrome” AND “systemic JIA” AND “treatment OR management OR biologic”. Articles evaluating biologics for sJIA associated MAS were included. Case reports and case series with fewer than 8 patients were excluded. Results: Of the 107 articles identified, 8 met the inclusion criteria. A total number of 90 sJIA-MAS unique patients were treated with biologics (55 Anakinra, 22 Tocilizumab, and 13 Emapalumab) (Table 1). Only one prospective open label study was identified evaluating emapalumab; the remaining studies were retrospective case series. Anakinra, assessed in 5 studies, showed an 87% complete response rate (43/55 cases) with 2 reported deaths. Tocilizumab, in 2 studies, had a 100% response rate but one unrelated death. Emapalumab showed a 93% response rate (12/13 cases) with no death. Conclusion: Biologic therapies against IL-1, IFN-γ, and IL-6 appear to be effective in sJIA associated-MAS. Anakinra is usually the first line biologic therapy. Emapalumab is a promising treatment in refractory MAS. High quality studies are urgently needed to support their use. REFERENCES: NIL. Table 1. Biologics in the management of sJIA associated MAS Study 1st author, publication year Country Biologic Study design Patients n. (female %) Age in years at MAS onset Drug dose, duration days mean (range) Complete response rate n. (%) Partial response rate, n. (%) Recurrence rate, n. (%) Follow in months, n.(range) Death n. (%) Miettunen, 2011 USA, Canada Anakinra Retrospective case series 8 (50%) 10.5 (mean) 2 mg/kg/day (max 100 mg daily), 13(2-19) 8 (100%) 0% 0% 22 (2-40) 0 (0) Somne, 2018 Turkey Anakinra Retrospective case series 13 (N/A) N/A Ν/Α 11 (85%) 0% 2 (15%) 13 (6-24) 0 (0) Eloseily, 2020 USA Anakinra Retrospective case series 13 (N/A) N/A 50-400 mg daily 13 (100%) N/A N/A N/A 0(0) Phadke, 2021 USA Anakinra IV Retrospective case series 10 (50%) 10 (mean) 1.7 to 15.4 mg/kg/daily, 6.4 (2-12) 9 (90%) N/A N/A N/A 1 (10%) Demir, 2022 Turkey Anakinra Retrospective case series 11 (N/A) 8 (median) N/A 7 (63%) 4 (37%) 2 (18%) 12 (N/A) 1 (9%) Zou, 2018 China Tocilizumab Retrospective case series 8 (N/A) N/A N/A 8 (100%) N/A N/A N/A N/A Wu, 2022 China Tocilizumab Retrospective case series 14 (42%) 6 (median) 12 mg/kg < 30 kg, 8 mg/kg >30 kg 14 (100%) 0% 0% 25 (3-60) 1 (7%) De Benedetti, 2023 Multinational Emapalumab Prospective, open label, single-arm trial 13 (N/A) 11 (median) 6mg/kg followed by 3 mg/kg every 3 days, 27 median (7-39) 12 (93%) 1 (7%) 4 (28%) 12 (N/A) 0 (0) Acknowledgements: NIL. Disclosure of Interests: None declared. DOI: 10.1136/annrheumdis-2024-eular.1591 Keywords: Systematic review, Biological DMARD Citation: , volume 83, supplement 1, year 2024, page 1379Session: Juvenile idiopathic arthritis (Publication Only)

Systematic review, Biological DMARD