Post-Authorisation Active Safety Surveillance Program Among Patients Treated With Tofacitinib for Polyarticular Juvenile Idiopathic Arthritis (pJIA) and Juvenile Psoriatic Arthritis (PsA) Within the United Kingdom (UK) Juvenile Idiopathic Arthritis (JIA) Biologics Register

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  XELJANZ
• Study drug International non-proprietary name (INN) or common name:
  TOFACITINIB CITRATE
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AA29) tofacitinib

  tofacitinib
• Medical condition to be studied:
  Juvenile idiopathic arthritis

  Juvenile psoriatic arthritis

Population studied

• Short description of the study population:
  The study population will comprise all patients with pJIA or juvenile PsA enrolled within the UK JIA Biologics Register who receive tofacitinib following product availability in the UK since 07 April 2022 through 01 July 2029. One comparator cohort comprised of patients with pJIA or juvenile PsA treated with approved bDMARDs (etanercept being the most prevalent bDMARD used within the UK registers) and identified from 01 January 2010 through 01 July 2029 will be assembled to provide context for rates observed among patients treated with; tofacitinib.
• Age groups:
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)

Study design details

• Study design:
  This is an active surveillance study utilizing data from the UK JIA Biologics Register, which consists of the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study and the Biologics for Children; with Rheumatic Diseases Study.
• Main study objective:
  To estimate the post-approval real-world IR of the following outcomes of interest among patients with pJIA or juvenile PsA who initiate tofacitinib (Tofacitinib cohort) and among patients with pJIA or juvenile PsA treated with approved bDMARDs (Comparator cohort):; Venous thromboembolism; Serious infections and other important infections (including opportunistic infection, tuberculosis and vaccine preventable infections); All malignancies combined (excluding NMSC); Lymphoma (examined as a separate outcome); Lung cancer (examined as a separate outcome)
• Setting:
  The study period will be defined from 07 April 2022 (corresponding to tofacitinib availability in the UK ) to 01 July 2030 for the tofacitinib cohort and from 01 January 2010 to 01 July 2030 for the comparator cohort. This study is set within the UK JIA Biologics Register. Data from the UK JIA Biologics Register has contributed to a range of publications focusing on real-world biologic treatment effectiveness and safety. Historically and due to the nature of prior funding, data on children with JIA starting biologics, targeted therapies and MTX were captured in 2 parallel but identical studies, both based at The University of Manchester. The BSPAR Etanercept cohort study; collects data from children starting etanercept or methotrexate. The BCRD Study collects data from children starting non-etanercept bDMARDS, including other tumor necrosis factor (TNF) inhibitors such as adalimumab, JAK inhibitors or MTX. Both studies operate under the single banner of the UK JIA Biologics Register. Patients can contribute data to both studies and data captured using identical methods from the same hospitals are pooled for analyses.
• Comparators:
  Patients with pJIA or juvenile PsA treated with approved bDMARDs (Comparator cohort):; 1. Diagnosis of pJIA defined as extended oligoarthritis, Polyarthritis (RF+), or Polyarthritis (RF-) or juvenile PsA by a rheumatologist; 2. Patients younger than 16 years at diagnosis of pJIA or juvenile PsA; 3. Patients aged 2-17 years at initiation of any bDMARD approved for pJIA or juvenile PsA treatment in UK (e.g., etanercept, adalimumab, abatacept, tocilizumab). This is first use of unique bDMARD, not restricted to first bDMARD use (i.e., not restricted to bDMARD naïve patients). For example, a patient starting etanercept for the first time during the period of 01 January 2010 to 01 July 2029 will be eligible regardless of this patient’s prior use of another bDMARD, for example tocilizumab.; 4. Patients initiating a bDMARD as a monotherapy or in combination with MTX during the study period from 01 January 2010 to 01 July 2029 and as captured in the UK JIA Biologics Register
• Outcomes:
  The following outcomes of interest will be examined in the interim and final study report. All outcomes, with the exception of growth or development disturbances, will be identified using the Medical Dictionary for Regulatory Activities (MedDRA) codes. Please see Annex 1 for relevant MedDRA codes.; Venous thromboembolism; Serious infections and other important infections (including opportunistic infection, tuberculosis and vaccine preventable infections); All malignancies combined (excluding NMSC); Lymphoma (examined as a separate outcome); Lung cancer (examined as a separate outcome); Gastrointestinal perforations; Major adverse cardiac events (including MI); Hypersensitivity; Growth or development disturbances; Fractures; PML; All-cause mortality; HZ reactivation; NMSC; Interstitial lung disease
• Data analysis plan:
  Crude incidence rates (IRs) of events overall and stratified by baseline characteristics such as disease activity, subtype of JIA, treatment type defined as monotherapy or combination therapy with MTX on the index date, and prior JIA therapy in both tofacitinib cohort and comparator cohort will be calculated. A comparative analysis will examine the risk of the outcomes of interest among patients from the tofacitinib cohort compared to the patients from the comparator cohort adjusting for confounding by baseline characteristics. Propensity scores will be estimated using baseline characteristics described in the study protocol. Propensity score adjusted IR (per 100 PY) and associated 95% CI will be calculated for the outcomes of interest, for which there are adequate data using an exact Poisson method. Where there are adequate data to compare the risk between cohorts, multivariable Cox proportional hazards models will be fit to compare risk of the outcome of interest.