title: Successful treatment with tocilizumab every 4 weeks of a low disease activity group who achieve a drug-free remission in patients with systemic-onset juvenile idiopathic arthritis.
abstract: BACKGROUND
  Systemic juvenile idiopathic arthritis (SoJIA) is the most striking form of juvenile idiopathic arthritis. The aim of our study was to evaluate the clinical responses and outcomes of children with SoJIA to IL-6 blockade using two different tocilizumab (TCZ) treatment protocols designed for milder and more severe SoJIA patient groups, and evaluate the possibility of achieving biologic-free remission.
  
  
  METHODS
  Thirty-seven active SoJIA children who have failed treatment with corticosteroids and other DMARDs were included in our retrospective study. TCZ doses were prescribed in two treatment approaches: every 2 weeks TCZ dosing (Q2W) and every 4 weeks TCZ dosing (Q4W). The patients were assigned to these two groups by the study physicians depending on the severity of the SoJIA disease as judged by each clinician.
  
  
  RESULTS
  Thirty-three of the 37 children successfully completed the trial. TCZ was discontinued in 11patients during the trial. Seven children achieved inactive disease and were allowed to stop the TCZ and 4 had severe adverse events requiring drug cessation. Currently 7 patients continue to have TCZ-free remission [4/7 remission off-medication, 3/7still on methotrexate (MTX)]. This mixed group had a median treatment duration of 1002 days. The children in remission off of all medications, TCZ and MTX, had a median remission duration of 1162 days (ranged 932-1301 days). Compared to the patients assigned to the Q2W TCZ treatment group, the patients assigned to the Q4W TCZ group had a milder SoJIA course. The patients had higher levels of hemoglobin, total proteins, and serum albumins. They had lower white blood cell counts (WBC), % granulocytes, CRP, ESR, ferritins, and LDH. These children had a lower frequency of internal organ involvement, fewer relapses during TCZ treatment, and no macrophage activation syndrome episodes.
  
  
  CONCLUSIONS
  Our experience with TCZ for SoJIA supports the excellent result of other studies. What may be novel is our finding that thisIL-6 blockade with TCZ may be able to be utilized at a less frequent dosing schedule in mild SoJIA compared to severe SoJIA. We discuss other factors that may increase the probability of a patient reaching TCZ-free remission.
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Mikhail M
authors: MM
authors: Kostik
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Margarita F
authors: MF
authors: Dubko
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Vera V
authors: VV
authors: Masalova
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Ludmila S
authors: LS
authors: Snegireva
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Tatyana L
authors: TL
authors: Kornishina
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Irina A
authors: IA
authors: Chikova
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Eugenia A
authors: EA
authors: Isupova
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Ekaterina M
authors: EM
authors: Kuchinskaya
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Natalia I
authors: NI
authors: Glebova
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Natalia V
authors: NV
authors: Buchinskaya
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Olga V
authors: OV
authors: Kalashnikova
authors: Hospital Pediatric Department, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg, 194100 Russia.
authors: Vyacheslav G
authors: VG
authors: Chasnyk
mesh_terms: D017668:Age of Onset; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000453:epidemiology*; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D012075:Remission, Spontaneous; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D008727:Methotrexate; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab
keywords: Biologic free remission; High disease activity; Interleukine-6; Low disease activity; Systemic-onset juvenile idiopathic arthritis; Tocilizumab