Response to Interleukin-1 Inhibitors in 140 Italian Patients with Adult-Onset Still's Disease: A Multicentre Retrospective Observational Study

被引：87

作者：

Colafrancesco, Serena ^{[1
]}

Priori, Roberta ^{[1
]}

Valesini, Guido ^{[1
]}

Argolini, Lorenza ^{[2
]}

Baldissera, Elena ^{[3
,4
]}

Bartoloni, Elena

Cammelli, Daniele ^{[5
,6
]}

Canestrari, Giovanni ^{[7
]}

Cantarini, Luca ^{[8
,9
]}

Cavallaro, Elena ^{[10
]}

Cavalli, Giulio ^{[3
,11
]}

Cerrito, Lucia ^{[12
]}

Cipriani, Paola ^{[13
]}

Dagna, Lorenzo ^{[3
,11
]}

De Marchi, Ginevra ^{[10
]}

De Vita, Salvatore ^{[10
]}

Emmi, Giacomo ^{[5
]}

Ferraccioli, Gianfranco ^{[7
]}

Frassi, Micol ^{[14
]}

Galeazzi, Mauro ^{[8
,9
]}

Gerli, Roberto ^{[4
]}

Giacomelli, Roberto ^{[13
]}

Gremese, Elisa ^{[7
]}

Iannone, Florenzo ^{[15
]}

Lapadula, Giovanni ^{[15
]}

Lopalco, Giuseppe ^{[15
]}

Manna, Raffaele ^{[12
]}

Mathieu, Alessandro ^{[16
]}

Montecucco, Carlomaurizio ^{[17
]}

Mosca, Marta ^{[18
]}

Piazza, Ilaria ^{[19
]}

Piga, Matteo ^{[16
]}

Pontikaki, Irene ^{[2
]}

Romano, Micol ^{[2
]}

Rossi, Silvia ^{[17
]}

Rossini, Maurizio ^{[19
]}

Ruscitti, Piero ^{[13
]}

Silvestri, Elena ^{[5
]}

Stagnaro, Chiara ^{[18
]}

Talarico, Rosaria ^{[18
]}

Tincani, Angela ^{[14
]}

Viapiana, Ombretta ^{[19
]}

Vitiello, Gianfranco ^{[6
]}

Fabris, Francesca ^{[20
]}

Bindoli, Sara ^{[20
]}

Punzi, Leonardo ^{[20
]}

Galozzi, Paola ^{[20
]}

Sfriso, Paolo ^{[20
]}

机构：

[1] Sapienza Univ Rome, Rheumatol Unit, Dept Internal Med & Med Specialties, Rome, Italy

[2] ASST Gaetano Pini, Div Rheumatol, Milan, Italy

[3] IRCCS, Unit Immunol Rheumatol Allergy & Rare Dis UnIRAR, San Raffaele Sci Inst, Milan, Italy

[4] Univ Perugia, Rheumatol Unit, Dept Med, Perugia, Italy

[5] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[6] AOU Careggi, Rheumatol Sect, Immunoallergol Unit, Florence, Italy

[7] Univ Cattolica Sacro Cuore, Inst Rheumatol & Affine Sci, Div Rheumatol, Rome, Italy

[8] Univ Siena, Res Ctr Syst Autoinflammatory Dis, Siena, Italy

[9] Univ Siena, Behcets Dis Clin Surg & Neurosci, Dept Med Sci Surg & Neurosci, Siena, Italy

[10] Univ Udine, Rheumatol Clin, Dept Med & Biol Sci, Udine, Italy

[11] Univ Vita Salute San Raffaele, Dept Internal Med, Milan, Italy

[12] Univ Cattolica Sacro Cuore, Inst Internal Med, Period Fever Res Ctr, Fdn Policlin A Gemelli, Rome, Italy

[13] Univ Aquila, Div Rheumatol, Dept Biotechnol & Appl Clin Sci, Laquila, Italy

[14] Univ Brescia, Rheumatol & Clin Immunol, Spedali Civili & Dept Clin & Expt Sci, Brescia, Italy

[15] Univ Bari, Interdisciplinary Dept Med, Rheumatol Unit, Bari, Italy

[16] Univ & AOU Cagliari, Rheumatol Unit, Dept Med Sci, Cagliari, Italy

[17] Univ Pavia, IRCCS, Dept Rheumatol, Policlin San Matteo Fdn, Pavia, Italy

[18] Univ Pisa, Dept Clin & Expt Med, Rheumatol Unit, Pisa, Italy

[19] Univ Verona, Dept Med, Rheumatol Unit, Verona, Italy

[20] Univ Padua, Dept Med DIMED, Rheumatol Unit, Padua, Italy

来源：

FRONTIERS IN PHARMACOLOGY | 2017年 / 8卷

关键词：

Adult-onset Still's disease; treatment; interleukin (IL)-1; anakinra; canakinumab; JUVENILE IDIOPATHIC ARTHRITIS; ANAKINRA; EFFICACY; CYTOKINE; MANIFESTATIONS; CANAKINUMAB; RESISTANT; DIAGNOSIS; PROFILES; AGENTS;

D O I：

10.3389/fphar.2017.00369

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: Interleukin (IL)-1 plays a crucial role in the pathogenesis of Adult onset Still's disease (AOSD). Objectives: To evaluate the efficacy and safety of anakinra (ANA) and canakinumab (CAN) in a large group of AOSD patients. Methods: Data on clinical, serological features, and concomitant treatments were retrospectively collected at baseline and after 3, 6, and 12 months from AOSD patients (Yamaguchi criteria) referred by 18 Italian centers. Pouchot's score was used to evaluate disease severity. Results: One hundred forty patients were treated with ANA; 4 were subsequently switched to CAN after ANA failure. The systemic pattern of AOSD was identified in 104 (74.2%) of the ANA-treated and in 3 (75%) of the CAN-treated groups; the chronicarticular type of AOSD was identified in 48 (25.8%) of the ANA-treated and in 1 (25%) of the CAN-treated groups. Methotrexate (MTX) was the most frequent disease modifying anti-rheumatic drug (DMARD) used before beginning ANA or CAN [91/140 (75.8%), 2/4 (50%), respectively]. As a second-line biologic DMARD therapy in 29/140 (20.7%) of the patients, ANA was found effective in improving all clinical and serological manifestations (p < 0.0001), and Pouchot's score was found to be significantly reduced at all time points (p < 0.0001). No differences in treatment response were identified in the ANA-group when the patients were stratified according to age, sex, disease pattern or mono/combination therapy profile. ANA primary and secondary inefficacy at the 12-month time point was 15/140 (10.7%) and 11/140 (7.8%), respectively. Adverse events (AEs) [mainly represented by in situ (28/47, 59.5%) or diffuse (12/47, 25.5%) skin reactions and infections (7/47, 14.8%)] were the main causes for discontinuation. Pouchot's score and clinical and serological features were significantly ameliorated at all time points (p < 0.0001) in the CAN-group, and no AEs were registered during CAN therapy. Treatment was suspended for loss of efficacy only in one case (1/4, 25%). Conclusion: This is the largest retrospective observational study evaluating the efficacy and safety of IL-1 inhibitors in AOSD patients. A good response was noted at 3 months after therapy onset in both the ANA-and CAN-groups. Skin reaction may nevertheless represent a non-negligible AE during ANA treatment.

引用

页数：12

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