LOOK-UP: Active pharmacovigilance study of the medicine Rinvoq™ (upadacitinib)

Study type

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  RINVOQ

  RINVOQ 15 MG - PROLONGED-RELEASE TABLET

  RINVOQ 30 MG - PROLONGED-RELEASE TABLET

  RINVOQ 45 MG - PROLONGED-RELEASE TABLET
• Study drug International non-proprietary name (INN) or common name:
  UPADACITINIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AF03) upadacitinib

  upadacitinib
• Medical condition to be studied:
  Rheumatoid arthritis

  Crohn's disease

  Dermatitis atopic

  Colitis ulcerative

  Psoriatic arthropathy

Population studied

• Short description of the study population:
  Patients will be included retrospectively and prospectively from the study start date from hospitals in the Porto district who cumulatively meet the following inclusion criteria: ; (i) medical prescription of Rinvoq™ from 1 January 2024; ; (ii) 18 years or older at the time of recruitment; ; and (iii) explicit consent to participate in the study.; ; Patients will be excluded if, at the time of recruitment: ; (i) they present any degree of cognitive impairment that prevents them from responding to a questionnaire administered by telephone; ; (ii) they are participating in a phase I, II, or III clinical trial; ; (iii) their life expectancy is less than 1 month; ; or (iv) they do not have a valid telephone contact.
• Age groups:
  Adult and elderly population (≥18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Frail population

  Hepatic impaired

  Renal impaired

Study design details

• Study design:
  An ambispective, multicentric cohort observational study, conducted as a Phase 4 post-authorisation safety study (PASS).
• Main study objective:
  Quantify the incidence of adverse events in patients with a medical prescription for Rinvoq™. ; Particular attention will be given to serious adverse events already described in the previous literature (malignant neoplasms, excluding non-melanoma skin cancer; non-melanoma skin cancer (NMSC); major adverse cardiovascular events (MACE); venous thromboembolism (VTE); serious and opportunistic infections, including herpes zoster and tuberculosis; gastrointestinal perforations; hepatic injuries, including drug-induced liver injury; bone fractures; all-cause mortality).
• Setting:
  The centers involved in the study will be exclusively hospital institutions. ; For the purposes of practicality and logistical efficiency, the selection of participating hospitals will be limited to the area affiliated with UFPorto, specifically the Porto district.
• Comparators:
  NA
• Outcomes:
  Primary outcome: incidence of adverse events that arise during the established follow-up period, coded according to MedDRA terminology.; ; Exploratory outcome: Rate of non-compliance with PRAC recommendations, i.e., quantify the frequency with which patients with identified risk factors receive a prescription for Rinvoq™ despite the existence of viable therapeutic alternatives. ; Patients with risk factors are considered to be: ; (i) patients aged 65 years or older; ; (ii) current smokers or those with a long history of smoking; ; (iii) individuals at high risk of serious cardiovascular problems, such as heart attacks or strokes; ; or (iv) those more likely to develop cancer.
• Data analysis plan:
  A descriptive analysis of the variables of interest will be conducted. ; Categorical variables will be presented through absolute and relative frequencies, and continuous variables through descriptive statistics such as mean and standard deviation, quartiles, median, and minimum and maximum values.; Sociodemographic data will be described using the above measures according to the characterisation of each variable. ; Clinical history information for each patient will also be detailed. Univariate and multivariate regression analyses will be conducted to evaluate the relationship between risk factors and adverse events, depending on the sample size to confer statistical power to these tests.; To address the primary objective of the study, incidence rates of adverse events will be estimated overall, as well as by subgroups. ; Sub-analyses stratified by clinical interest variables such as severity of events, dosage of Rinvoq™ (15mg, 30mg, 45mg), allergy history, among others, will be conducted.; Survival analysis will be performed to evaluate the time to occurrence of adverse events, allowing the identification of temporal patterns in adverse events, considering the possibility of data censoring (for example, when patients are no longer followed in the study due to dropout or other reasons). ; Kaplan-Meier curves will be used to graphically illustrate the cumulative probability of non-occurrence of adverse events over time. ; Additionally, statistical tests such as the log-rank test will be used to compare survival curves between different patient subgroups, identifying significant differences in adverse event incidence between these groups. ; When appropriate, Cox proportional hazards modelling will be used to evaluate the impact of specific variables such as age, sex, comorbidities, and other relevant factors on the risk of adverse events.; Finally, subgroup and sensitivity analyses will also be considered.