Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study

• DOI: 10.3389/fmed.2023.1257045
• Publication Date: 2023-11-15T13:39:58Z
• Authors: Ekaterina Alexeeva; Meiri Shingarova; Tatyana Dvoryakov...; Olga Lomakina; Anna Fetisova; Ksenia Isaeva; Aleksandra Chomak...; Kristina Chibisova; Elizaveta Krekhova; Aleksandra Kozodaeva; Kirill Savostyanov; Aleksandr Pushkov; Ilya Zhanin; Dmitry Demyanov; Evgeny Suspitsin; Konstantin Belozerov; Mikhail Kostik
• Keywords: Canakinumab; Lymphoplasmacytic Lymphoma; myalgia

Introduction The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D cryopyrin-associated but this treatment has not been assessed patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety efficacy canakinumab uAIDs. Methods Information on 32 uAIDs was retrospectively collected analyzed. Next-generation sequencing Federici criteria were used exclusion known AID. Results median age first episode 2.5 years (IQR: 1.3; 5.5), that disease diagnosis 5.7 2.5;12.7), diagnostic delay 1.1 0.4; 6.1). Patients had variations in following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1 , SLC7A7 . main clinical features fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart (31%), intestinal (19%); eye (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), failure thrive (25%). Initial before consisted non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide sulfasalazine mycophenolate mofetil hydroxychloroquine biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, infliximab (all 3%). Canakinumab induced complete remission 27 (84%) partial one patient (3%). Two primary non-responders, two further developed secondary inefficacy. All or inefficacy switched ( n = 4) sarilumab 1). total duration 3.6 (0.1; 8.7) years. During study, there no reported Serious Adverse Events (SAEs). experienced non-frequent mild respiratory infections at rate similar administered. Additionally, leucopenia, it necessary stop patient. Conclusion using safe effective. Further randomized trials are required confirm safety.