AUTHOR=Alexeeva Ekaterina , Shingarova Meiri , Dvoryakovskaya Tatyana , Lomakina Olga , Fetisova Anna , Isaeva Ksenia , Chomakhidze Aleksandra , Chibisova Kristina , Krekhova Elizaveta , Kozodaeva Aleksandra , Savostyanov Kirill , Pushkov Aleksandr , Zhanin Ilya , Demyanov Dmitry , Suspitsin Evgeny , Belozerov Konstantin , Kostik Mikhail 

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

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1257045

DOI=10.3389/fmed.2023.1257045

ISSN=2296-858X

ABSTRACT=Introduction: the blockade of interleukine-1 (anakinra and canakinumab) is a known highly effective tool for monogenic autoinflammatory diseases (AID), such as familial mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AID (uAID).
Our study aimed to assess the safety and efficacy of canakinumab for patients with uAID.
Methods:  The information on 32 patients affected by uAID was retrospectively collected and analyzed. Next generation sequence and Federici criteria used for exclusion of the known monogenic AID.
Results: The median age of the first episode was 2.5 years (IQR:1.3; 5.5), of the disease diagnosis - 5.7 years (IQR:2.5;12.7) and diagnostic delay was 1.1 years (IQR:0.4; 6.1). Patients have variants in the 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.The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement 9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), failure to thrive (25%).
Initial treatment before canakinumab consisted of non-biologic: NSAID (91%), corticosteroids (88%), methotrexate (38%), IVIG (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%) and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, infliximab (all 3%). Canakinumab induced complete remission in 27 (84%), partial in one patient (3%). Two patients (6%) were primary non-responders and two (6%) developed secondary inefficacy further. All patients with partial efficacy or with inefficacy switched to tocilizumab (n=4) and sarilumab (n=1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported SAEs. Patients had non-frequent mild respiratory infections with a similar rate as before canakinumab and one patient developed leucopenia, not required to stop canakinumab.
Conclusion: the treatment of patients with uAID with canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.