Herpes zoster and other opportunistic infections in patients with inflammatory bowel disease in Norway – associations with immunosuppressive treatment (NOZOIBD)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  TOFACITINIB

  INFLIXIMAB
• Medical condition to be studied:
  Crohn's disease

  Colitis ulcerative

Population studied

• Short description of the study population:
  The study population includes all patients in Norway registered with IBD (ICD code K50 or K51) and aged ≥18 years in NPR in the time period between 2008 and 2019 that do not meet any exclusion criteria; Inclusion Criteria; All patients who are registered with at least 1 diagnosis of IBD (ICD-code K50 or K51) and aged ≥18 years in NPR during the study period 2008-2019.; Exclusion Criteria; Patients meeting any of the following criteria will not be included in the study:; 1. A single hospital discharge diagnosis of IBD (ICD-code K50 or K51) and no pharmacy claim for IBD medication (eg, 5-ASA, thiopurines, anti-TNF, enteral budesonide) (indicates that initial diagnosis of IBD was wrong). ; 2. Diagnosis of HIV-infection (ICD B25, R75), cancer (ICD C00-C97), organ transplantation (ICD Y830) or congenital immunodeficiency (ICD D80-D84) (confounds the study since these are independently associated with increased risk of HZ and other OI).
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Patients with Crohn's disease, Colitis ulcerative
• Estimated number of subjects:
  55000

Study design details

• Main study objective:
  The project aims to quantify the burden of herpes zoster and other opportunistic infections (i.e. incidence rates and rate of complications), including the association with immunosuppressive treatment, in Norwegian patients with inflammatory bowel disease.
• Outcomes:
  The incidence rate of HZ, including the rate of recurrent events, rates of disseminated HZ and complications (e.g. postherpetic neuralgia) and the incidence rate of other OI (e.g. C. difficile, CMV, fungal infections) in Norwegian IBD patients. • The association between medical treatment (glucocorticoids, thiopurine, methotrexate, anti-TNF, anti-TNF+thiopurine, vedolizumab, ustekinumab and tofacitinib) and incidence of HZ and other OI. • The proportion of HZ events in IBD patients managed in general practice vs in hospitals. • The proportion of IBD patients that are receiving anti-viral therapy for HZ events.
• Data analysis plan:
  Categorical variables will be described with the number of values, percentages and as incidence rate/1000 patient years. Data will also be calculated according to age categories. To assess the association between medical treatment (glucocorticoids, thiopurines, methotrexate, anti-TNF, anti-TNF+thiopurine, vedolizumab, ustekinumab and tofacitinib) and incidence of HZ or other OI, we will do a Cox regression with both fixed and time-dependent covariates. This entails following the patients from their first IBD diagnosis to their first diagnosis of HZ or other OI, adjusting for other covariates (age, gender, treatment both current and prior). Results will be presented as multivariable adjusted hazard ratios and survival plots.