title: Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still's disease: multicenter retrospective open-label study of thirty-four patients.
abstract: 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 women) was 38.7 ± 16.1 years. The median duration of AOSD before TCZ was initiated was 4.2 years (interquartile range [IQR] 1-9 years). The initial dosages of intravenous TCZ were 8 mg/kg every 4 weeks in 22 patients, 4 mg/kg every 4 weeks in 2 patients, and 8 mg/kg every 2 weeks in 10 patients. TCZ treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. After 1 year of TCZ therapy, the incidence of joint manifestations had decreased from 97.1% at baseline to 32.4%, the incidence of both cutaneous manifestations and fever had decreased from 58.8% to 5.9%, and the incidence of lymphadenopathy had decreased from 29.4% to 0%. A dramatic reduction in laboratory markers of inflammation, including the C-reactive protein level, the erythrocyte sedimentation rate, and the ferritin level, was achieved. The median dosage of prednisone was also reduced, from 13.8 mg/day (IQR 5-45) at the initiation of TCZ to 2.5 mg/day (IQR 0-30) at 12 months. After a median followup of 19 months (IQR 12-31 months), only 2 patients required permanent discontinuation of TCZ therapy because of severe infections.
  
  
  CONCLUSIONS
  TCZ treatment was associated with rapid and maintained clinical and laboratory improvement in patients with AOSD refractory to standard treatment. However, joint manifestations seem to be more refractory to treatment compared with systemic manifestations.
authors: Hospital Universitario Marqués de Valdecilla and Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
authors: Francisco
authors: F
authors: Ortiz-Sanjuán
authors: Ricardo
authors: R
authors: Blanco
authors: Vanesa
authors: V
authors: Calvo-Rio
authors: Javier
authors: J
authors: Narvaez
authors: Esteban
authors: E
authors: Rubio Romero
authors: Alejandro
authors: A
authors: Olivé
authors: Santos
authors: S
authors: Castañeda
authors: Adela
authors: A
authors: Gallego Flores
authors: M Victoria
authors: MV
authors: Hernández
authors: Cristina
authors: C
authors: Mata
authors: Inmaculada
authors: I
authors: Ros Vilamajo
authors: Walter Alberto
authors: WA
authors: Sifuentes Giraldo
authors: Miguel A
authors: MA
authors: Caracuel
authors: Mercedes
authors: M
authors: Freire
authors: Catalina
authors: C
authors: Gómez Arango
authors: José
authors: J
authors: Llobet
authors: Sara
authors: S
authors: Manrique Arija
authors: Carlos
authors: C
authors: Marras
authors: Concepción
authors: C
authors: Moll-Tuduri
authors: Chamaida
authors: C
authors: Plasencia-Rodriguez
authors: Rosa
authors: R
authors: Roselló
authors: Ana
authors: A
authors: Urruticoechea
authors: Maria L
authors: ML
authors: Velloso-Feijoo
authors: Jordi
authors: J
authors: Del Blanco
authors: M Carmen
authors: MC
authors: González-Vela
authors: Javier
authors: J
authors: Rueda-Gotor
authors: Trinitario
authors: T
authors: Pina
authors: Javier
authors: J
authors: Loricera
authors: Miguel A
authors: MA
authors: González-Gay
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000276:immunology; D012189:Retrospective Studies; D016706:Still's Disease, Adult-Onset / Q000188:drug therapy*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D019947:Receptors, Interleukin-6; C502936:tocilizumab