TG1101-RMS402

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:
  BRIUMVI
• Study drug International non-proprietary name (INN) or common name:
  UBLITUXIMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AG14) ublituximab

  ublituximab
• Medical condition to be studied:
  Relapsing-remitting multiple sclerosis

Population studied

• Short description of the study population:
  Adult patients diagnosed with relapsing multiple sclerosis (RMS)
• 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)
• Estimated number of subjects:
  1772

Study design details

• Study design:
  This will be a multi-registry, multi-centre, long-term, observational study of adult RMS patients (≥18 years) treated with ublituximab or comparator RMS standard of care medication.
• Main study objective:
  The overall objective of the study is to characterize the long-term safety of ublituximab in adult patients diagnosed with relapsing multiple sclerosis (RMS) in a post-approval real-world setting.;
• Setting:
  The study population will consist of adult RMS patients (≥18 years) divided into 3 study cohorts for ; delayed-onset outcomes and 3 study cohorts for acute-onset outcomes, i.e., patients treated with ublituximab, patients treated with other anti-CD20 treatments, and patients treated with other standard RMS treatments acting through a different mechanism that are approved in the countries participating in the study at the time of patient enrolment.
• Comparators:
  Other DMTs
• Outcomes:
  Total malignancy includes skin cancers, solid cancers, and hematologic cancers. Cases of malignancy will be identified using the Medical Dictionary for Regulatory Activities (MedDRA) Standardised MedDRA query (SMQ) “Malignancy”. Total malignancy events including NMSC (defined in Section 9.3.2.2.1. will be assessed in the primary analysis. ; ; Malignancy excluding NMSC includes solid cancers and hematologic cancers. Cases of ; malignancy will be identified using the MedDRA SMQ “Malignancy”. All malignancy events ; excluding NMSC (defined in Section 9.3.2.2.1. will be assessed in the primary analysis.; ; Serious infections include infections requiring or prolonging hospitalisation; life-threatening ; infections; infections leading to death; infections causing disability; infections causing permanent ; damage or congenital abnormality; or medically significant infections (e.g., infections requiring ; parenteral or intravenous antibiotics). Cases of serious infection will be identified using the ; MedDRA System Organ Class (SOC) “Infections and Infestations”. All serious infection events ; will be assessed in the primary analysis. Serious infection sub-categories including but may not ; be limited to PML (treated as a delayed onset outcome) and hepatitis B reactivation will also be ; assessed.
• Data analysis plan:
  Analyses will be conducted separately for each outcome by the GMSR or the respective registry or its ; subcontractor and will include descriptive analyses, comparative analyses (where appropriate), and any relevant sensitivity analyses. ; Descriptive statistics will include percentages, means with standard deviations, and event incidence rates. Baseline tables will include the number of patients contributing multiple exposure episodes, including those patients who begin in the comparator cohort(s) before contributing to the ublituximab cohort and those patients who only contribute exposure episodes to the comparator cohort(s).; Propensity scores will be calculated for each exposure episode and used to create a common support population and address imbalances in the patient population that may confound the association between treatment and study outcomes. ; Inferential statistics include hazard ratios from frailty Cox proportional hazard models and a two-sided type I error rate of 0.05 will be used. Including the frailty term in the Cox model accounts for the possibility of multiple exposure episodes per patient per cohort when the PS model is applied to the exposure-level dataset. ; The proportional hazards assumption will be evaluated prior to fitting the Cox model. Details of the ; statistical approach are provided in the following sections. For all analyses, ublituximab will be the treatment of interest and the comparator cohort (either other DMT or other anti-CD20 treatments) will be the reference group. Comparisons with patients receiving other anti-CD20s is intended to provide information about the potential risk of secondary outcomes associated with ublituximab that may not be found with a comparison to other DMT medications. The GMSR will conduct its analyses in R Stat (R Core Team 2021).