Anti-IL-5/5R versus anti-IL4R switching strategies for uncontrolled severe asthma treated by anti-IL5/5R : A target trial emulation (RAMSES-Switch)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (R03DX09) mepolizumab

  (R03DX10) benralizumab

  (D11AH05) dupilumab
• Medical condition to be studied:
  Asthma

Population studied

• 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)
• Estimated number of subjects:
  200

Study design details

• Main study objective:
  In severe asthma patients after first failure of an anti-IL5/anti-IL-5R (mepolizumab or benralizumab), we aim to compare the variation of asthma control, measured by ACT, of two switching strategies : switching from anti-IL5/anti-IL-5R to an anti-IL4R (dupilumab) vs. switching from anti IL5/anti-IL-5R to another anti-IL5/anti-IL-5R.
• Outcomes:
  Change in Asthma Control Test (ACT). Time Frame 6 months. ACT >20 (n,%) Time frame 6 mo for all outcomes Change in Annual asthma exacerbation rate, in Annual asthma severe exacerbation rate,in maintenance oral corticosteroids dose, in Forced expiratory volume in one second, Asthma Quality of Life Questionnaire, inSino-nasal Outcome Test 22, in Blood eosinophil count Maintenance of treatment at time of switch +Exploratory outcomes
• Data analysis plan:
  Patient characteristics will be described .Use of Target trial emulation framework and propensity score framework for potential cofounders. Marginal effect will be estimated via linear regression model, adjusted on the propensity score applying IPTW (ATE). Bootstrap will be performed to estimate robust variances. Secondary endpoints analysis will involve logistic regression for binary variables, linear regression for continue variables in the weighted populations. Kaplan-Meier estimator is used to estimate survival probabilities over time. Missing data on covariates and outcomes will be managed by multiple imputations assuming data will be missing at random. Causal contrasts : modified intention-to-treat analysis. 3 Subgroups analysis according to history of chronic rhinosinusitis, treatment before the switch, and history of treatment by omalizumab. Sensitivity analysis, restriction to switches after 2020 and using an IPTW to get an ATT.