A Post-Authorization Safety Study of Golimumab in Ulcerative Colitis Using the Spanish ENEIDA Registry

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

  Other
• Non-interventional study design, other:
  Long-term observational, post-authorization safety study

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (L04AB06) golimumab

  golimumab
• Medical condition to be studied:
  Colitis ulcerative

Population studied

• Short description of the study population:
  The study population comprised of patients aged 18 years or older diagnosed with ulcerative colitis (UC) received treatment with golimumab (GLM), an anti-TNF agent other than GLM, or thiopurine between 19 September 2013 (date of GLM EU approval for UC) through 31 December 2021 identified from the ENEIDA registry.; Inclusion Criteria:; • Patient with UC in a research-quality site. ; • Aged 18 years or older at the date of study drug initiation.; • Qualified for one of the cohorts between 19 September 2013 and 31 December 2021. ; • Date of first prescription of cohort-defining drug (index date) occurred within a clinically credible period (< 6 months) after the last recorded clinic visit in ENEIDA. Index dates beyond this range raise concerns that the clinical record for this patient may be incomplete. ; Exclusion criteria: ; • Initiation of study drugs for indications other than UC, such as rheumatoid arthritis or psoriasis. ; • Evidence of any of the study outcomes before cohort entry: ; o Complete or partial colectomy; o ACN; o HSTCL; • For each of the 3 cohorts (ie, GLM, other anti-TNF, and thiopurine), if the patient initiated the drug defining the corresponding cohort for the first time before 19 September 2013. In other words, patients did not qualify for entry into a cohort if they were prevalent users of that drug before the study start date. However, patients could enter the study later based on subsequent initiation of other cohort-defining drugs. ; • If, prior to cohort entry, patients had initiated a novel biological or immunomodulator agent, for example:; o Vedolizumab: Entyvio® ; o Natalizumab: Tysabri®, Antegren® ; o Denosumab: Prolia®, Xgeva® ; o Etrolizumab: Raptiva®; o Tocilizumab: Actemra®, RoActemra®; o Ustekinumab: Stelara®; o Certolizumab: Cimzia®; o Tofacitinib: Xeljanz®; This list defines the drugs referred to as “vedolizumab and other novel immunomodulators” mentioned in the protocol and covers drugs that would likely be prescribed to patients with more severe UC and that are potentially related to the study outcomes.
• 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 ulcerative colitis
• Estimated number of subjects:
  3200

Study design details

• Main study objective:
  This study seeks to evaluate whether the use of GLM is associated with a risk of colectomy for intractable disease, advanced neoplasia (colorectal cancer or high grade dysplasia), and HSTCL in patients with UC as compared with alternative therapies for similar severity of disease. No a priori hypotheses will be evaluated.
• Outcomes:
  Colectomy due to intractable disease, Composite advanced colonic neoplasia (Colorectal cancer or High-grade colorectal dysplasia), Colorectal Cancer, Hepatosplenic T-cell Lymphoma
• Data analysis plan:
  All analyses will be conducted based on automated registry data, except for the nested-case control analysis. Baseline analyses will describe each cohort by patient characteristics. For each inception cohort, annual enrolment will be described, along with the frequency of study outcomes and cumulative person-years of follow-up accrued. The incidence rate of primary and secondary outcomes will be estimated for each inception cohort. The cumulative incidence of primary and secondary outcomes will be estimated using time-to-event analyses, overall by inception cohorts and then in stratified analyses. Stratification factors will be evaluated one at a time and will include gender, time since initial UC diagnosis, history of primary sclerosing cholangitis, UC hospitalization, and previous use of systemic steroids. Separate nested case-control analyses are planned to evaluate the association between study exposures and the two primary outcomes, colectomy for intractable disease and ACN.