Background Interleukin-1 inhibitor Canakinumab (a humanized anti- Il-1β monoclonal antibody) is gaining wider use in Russian clinical practice recently for treatment of auto-inflammatory diseases (AIDs). Experience with Canakinumab for systemic juvenile idiopathic arthritis (SoJIA), considered as AIDs, is being accumulated as first and second line biologic agents therapy. In Russia Canakinumab was initially marketed in 2011 for cryopyrin-associated periodic syndromes (CAPS), in 2013 – for SoJIA.
Objectives To assess efficacy and tolerability of Canakinumab in AIDs and SoJIA patients in clinical practice.
Methods Use Canakinumab at our Institute was commenced in 2012 y. The study included 19 pts, among them 12 had AIDs (including CAPS – in 8 pts: MWS – in 6, and CINCA/NOMID- in 2 pts; TRAPS - in 3 pts; Schnitzler syndrome – in 1), 7 pts had SoJIA. Among AIDs pts there were 7 females and 5 males, 9 pediatric and 3 adult pts, 2 pts from pediatric population getting adult by the time of analysis. Mean AIDs pts age at inclusion was 18,6 y (3–44), infantile disease onset was recorded in 9 pts, in 6 out of them – it was a neonatal onset from the moment of birth. Two familial MWS cases were included. Disease duration ranged from 3 to 44 years. Genetic mutations were established in 9 pts, including: gene NLRP3- 6 (Thr436Ile, Thr438Ile, Thr350Met – in 4 pts (two familial cases)), gene TNFRSF1A - 3 (His51Tyr, Cys59Arg, Cys99Arg). All AIDs pts presented with rash, fever, conjunctivitis or uveitis (8), neurosensory deafness (4), arthritis symptoms (9), lymphadenopathy (7), CNS involvement in 2, abdominal pain (5), stomatitis (4), physical retardation in CINCA/NOMID pts, intellectual retardation and cognitive impairment in 1 patient. SoJIA pts were aged 3,5 -17,5 y.o. predominantly males (5), with disease duration 1 - 16 y. All pts presented with systemic manifestations, 4 pts had severe polyarthritis. Increased levels of acute phase markers were documented in all pts. Canakinumab efficacy was estimated based on changes in ESR, CRP and WBC count vs baseline.
Results Canakinumab was administered s/c at 2–4mg/kg (max 150 mg) once every 8 weeks in AIDs pts, and at 4–6mg/kg (max 300mg) once in every 4 weeks in SoJIA pts. Canakinumab therapy duration in AIDs pts varied from 3mo to 2,5y, in SoJIA pts – from 9mo to 4y. Rapid clinical improvement was documented in all pts, with resolution of systemic manifestations and normalizing levels of acute phase markers. Prolonged ESR and CRP normalization was observed in one CINCA/NOMID patient. In 4 SoJIA pts arthritis manifestations were not sufficiently controlled. Canakinumab tolerability was satisfactory in all AIDs and SoJIA pts. No serious adverse reactions were documented. Canakinumab discontinuation in one SJIA patient was associated with secondary drug failure and onset of macrophages activation syndrome (MAS).
Conclusions The single Federal Center experience with Canakinumab in clinical practice in AIDs and SoJIA pts demonstrated high efficacy and good tolerability of this medication. No serious adverse events were noted. In SoJIA pts Canakinumab use should be viewed as possible option at early stages of the disease with systemic and initial joint involvement, whilst efficacy in pts with advanced arthritis turned out to be insufficient.
Disclosure of Interest None declared