Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients.Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent.Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2–6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3–47.5] mg/day at ANK onset to 5 [0–10] at 12 months. After a median [IQR] follow-up of 16 [5–50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5).ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.
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
Background Adult-onset Still's disease (AOSD) is frequently refractory to standard therapy. Anakinra (ANK) is an interleukin-1 (IL-1) receptor antagonist. The ANK has demonstrated efficacy in single cases or in small series of AOSD. We assessed the efficacy of ANK in a multicenter study. Objectives We assessed the efficacy of ANK in a multicenter study. Methods Retrospective open-label study of 34 patients with AOSD. ANK was used because of inadequate response to corticosteroids and at least 1 standard synthetic immunosuppressive drug, and in many cases also to biologic agents. Results Patients (22 women/12 men) had a mean age of 33.1±13.2 years and a median [interquartile range- IQR] AOSD duration of 1.6 [0.1-24] years before ANK onset. At ANK onset, the most frequent clinical manifestations were: joint manifestations (n=30), fever (n=25) and cutaneous manifestations (n=20). In reference to laboratory parameters, high C reactive protein (CRP) (n=31), high erythrocyte sedimentation rate (ESR) (n=27), leukocytosis (n=22) or anemia (n=18). ANK yielded rapid and maintained clinical and laboratory improvement (Table). After one year of ANK therapy, joint manifestations had decreased from 88.2% to 17.6%, fever from 73.5% to 5.9%, cutaneous manifestations from 58.8 to 2.9%, and lymphadenopathy from 20.6% to 0%. Also, a dramatic reduction of laboratory markers of inflammation including CRP, ESR and ferritin was achieved. The median [IQR] dose of prednisone was also reduced from 20 [0-100] mg/day at ANK onset to 5 [0-40] at 12 months. After a median [IQR] follow-up of 16 [1-206] months, the most important side effects were: cutaneous (n=6), mild leukopenia (n=2), myopathy with elevation of muscle enzymes (n=1), phalanx osteomyelitis (n=1) and urinary tract infection (n=1). Table 1 Baseline (N=34) Month 1 (N=34) Month 3 (N=30) Month 6 (N=25) Month 12 (N=21) Patients with joint manifestations, % 88.2% 47.1% 35.3% 20.6% 17.6% Patients with fever, % 73.5% 17.6% 11.8% 0% 5.9% Patients with cutaneous manifestations , % 58.8% 5.9% 11.8% 0% 2.9% Leucocytosis/mm3, mean ± SD 14949.7±7214.6 8171±3669.1 7732.7±3106.3 7633.5±2399.5 7885±2822.2 ESR (mm/1st hour), median [IQR] 63 [1–122] 16 [1–95] 14 [1–120] 8 [1–75] 5.5 [1–104] CRP (mg/dL), median [IQR] 6.8 [0.07–37.7] 0.6 [0.02–14] 0.5 [0.02–31.5] 0.4 [0.03–17] 0.2 [0.02–22] Prednisone dosage, median [IQR] 20 [0–100] 15 [0–100] 10 [0–60] 5 [0–15] 5 [0–40] Conclusions ANK is associated with rapid and maintained clinical and laboratory improvement in refractory AOSD. However, joint manifestations seem to be more refractory than systemic manifestations. Acknowledgements This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5607
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