Objective. Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment.Methods. This was a retrospective open-label study of TCZ treatment in 34 patients with AOSD who had experienced an inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug and also, in many cases, biologic agents.Results. The mean ؎ SD age of the patients (8 men and 26
Background
Adult-onset Still’s disease (AOSD) is often refractory to standard immunosuppressive therapy. Tocilizumab (TCZ) has shown efficacy in isolated cases or in small series.
Objectives
We assess the efficacy of TCZ in AOSD.
Methods
Multicenter study of 27 patients with AOSD of 18 hospitals diagnosed according to Yamagouchi’s criteria (J Rheumatol 1992;19:424). TCZ was used due to lack of good response to standard therapy or to other biologic agents.
Results
The 27 patients (20 women/ 7 men), had a mean age of 37.2±15.9 (range 16-71) and an average duration of AOSD of 5.9±4.6 years (range 0.1-17) to onset of TCZ. Prior to the onset of TCZ and besides corticosteroids, patients had recived the following drugs: Metotrexate (26 patients), Anakinra (12), Etanercept (6), Adalimumab (5) and Infliximab (3). TCZ standard dose was 8 mg/k/iv/4 weeks.
At TCZ onset, the most frequent clinical manifestations were joint (27 cases), cutaneous (14) and fever (18), along with analytical abnomalities, increase of ESR or CRP (20 cases), anemia (11) or leukocytosis (15). Clinical and analytical improvement was observed soon, 1st month after the onset of TCZ therapy (TABLE). After a mean follow-up of 20.8±12 months, cutaneous manifestations disappeared in 13 of 14 patients (92,9%), fever in 17 of 18 (94.4%) and joint manifestation in 22 of 27 (81,5%). Improvement of analytical abnormalities was observed in most cases with normalization of the blood cell count in 9 of 15 (60%) patients, anemia in 11 of 11 (100%), ESR in 15 of 19 (78.9 % ), CRP in 17 of 20 (85%), hepatic enzymes (AST/ALT) in 3 of 4 (50 %) and ferritin seric levels in 11 of 13 (84,6%). The median [IQR] dose of steroids was reduced from 15 [8.8-25] to 5 [1.3-7.5].
Conclusions
In refractory AOSD, TCZ yields early and maintained clinical-analytical response, even in refractory cases to other biological agents. Although TCZ showed global efficacy, joint are more refractory than other systemic manifestations.
Disclosure of Interest
None Declared
BackgroundInterleukin (IL)-1 and IL-6 are pivotal cytokines in the pathogenesis of adult-onset Still's disease (AOSD).ObjectivesCompare the efficacy and safety of tocilizumab (TCZ) versus anakinra (ANK) given for at least 1 year to AODS patients refractory to conventional treatment.MethodsMulticenter study (31 hospitals) of 75 patients (TCZ; n=34 and ANK; n 41) with AODS refractory to conventional immunosuppressive drugs and in many cases also to other biological agents.ResultsComparisons of the group of patients with TCZ and ANK were: a) Average age: 39±16 vs. 34±14 years (p=0.2) b) Percentage of women: 76.5% vs. 63.4% (p=0.2) c) Median disease duration 4.2 [1-9] vs. 2.2 [0.3 to 4.9] years (p=0.14) d) Average dose of prednisone 15±9.9 mg/day vs. 28.3±22 mg/day (p=0.013) e) Median of conventional immunosuppressants (2 [1-3] vs 1 [1-2] (p=0.05) f) Median of other biological therapies: 1 [0-2] vs. 0 [0-1] (p=0.04). The initial dose of i.v. TCZ were: 8 mg/kg/4 weeks (n=22), 8 mg/kg/2 weeks (n=10) and 4 mg/kg/4 weeks (n=2). ANK dose was 100 mg/day s.c. Both biologic agents were often combined with a conventional immunosuppressive drug (55.9% vs 70.7%; p=0.2). Both biologic agents yielded a quick and sustained improvement of all clinical and laboratory parameters (Table). The improvement in the clinical parameters was similar in both groups. However an earlier improvement of CRP and ESR was observed following TCZ therapy. After a median follow-up of 19 months [12-31] with TCZ and 15.5 months [4.5 to 50] with ANK (p=0.1), the major adverse effects in the TCZ group were: elevation liver enzymes (n=4), mild to moderate leucopenia (4), upper respiratory tract infection (3), pneumonia (1), pyelonephritis and severe enterocolitis (1) and spondylodiscitis (1). In the group of ANK: skin lesions (n=8), mild leucopenia (3), myopathy (1), respiratory infection by P. aeruginosa and gluteal abscess (1), herpes zoster (1), osteomyelitis (1) and infection of urinary tract (2). While none of the TCZ-treated required discontinuation of the drug due to inefficacy, ANK had to be discontinued for this reason in 11 patients (p=0.001). Adverse effects leading to discontinuation of the drug were observed in 2 patients with TCZ and 4 patients with ANK (p=0.54).ConclusionsTCZ and ANK are associated with a rapid and sustained clinical improvement in most patients with refractory AODS. However, TCZ appears to be more effective than ANK.Disclosure of InterestNone declared
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