Clinical trial NCT06485674: Long-Term Organ Damage: Anifrolumab Versus Real-World Standard of Care in Adult Patients With Active Systemic Lupus Erythematosus
Official title: Long-Term Organ Damage: Anifrolumab Versus Real-World Standard of Care in Adult Patients With Active Systemic Lupus Erythematosus (LASER) An External Comparator Arm Study for the TULIP Trials Using the University of Toronto Lupus Clinic Cohort
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Long-Term Organ Damage in Adult Patients With Active Systemic Lupus Erythematosus
Keywords: Anifrolumab
Active Systemic Lupus Erythematosus
Long-Term Organ Damage
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: IQVIA Pvt. Ltd
name: University Health Network, Toronto
First posted: 2024-07-03
Enrollment: 478
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All patients who initiated 300mg of anifrolumab in TULIP-1 or -2 will be included in the active treatment arm of this ECA study. To identify a comparator cohort of patients in the UTLC who would be considered eligible for the TULIP trials, all patients in the UTLC who were active in the database during the study time period (1 January 1995 to 31 December 2023) will be extracted,4 and all key eligibility criteria from TULIP-1 and -2 will be applied to patients in the UTLC.

Brief summary: This is an External control arm study to generate evidence on the comparative effect of anifrolumab plus Standard of Care in TULIP versus Real World Standard of Care on organ damage in adult patients with moderately to severely active Systemic lupus erythematosus (SLE). Patients who initiated 300 mg of anifrolumab in TULIP-1 or -2 will be indexed at the date of initiating anifrolumab and will be followed up until the earliest occurrence of death, loss to follow-up, trial dis-enrollment, or week 208 assessment (in LTE study).

Detailed description: This is an External Control arm study to generate evidence on the comparative effect of anifrolumab plus Standard of Care in TULIP versus Real World Standard of Care on organ damage in adult patients with moderately to severely active (Systemic lupus erythematosus) SLE. Patients who initiated 300 mg of anifrolumab in TULIP-1 or -2 will be indexed at the date of initiating anifrolumab and will be followed up until the earliest occurrence of death, loss to follow-up, trial dis-enrollment, or week 208 assessment (in LTE study). Patients in the University of Toronto Lupus Clinic will be indexed at the first date of clinical assessment within the patient enrollment period for which they satisfy all eligibility criteria and are receiving at least one eligible SOC treatment (i.e., their 'index assessment') and will be followed up until the earliest occurrence of death, loss to follow-up, UTLC disenrollment, or end of study period.

Eligibility criteria: Inclusion Criteria for UTLC:

1. Aged 18 through 70 years at index date.
2. Weight ≥40.0 kg at index date.
3. Diagnosis of paediatric or adult SLE ≥24 weeks prior to index date using ≥4 of the 11 modified ACR classification criteria at least one of which must be positive antinuclear antibody test, anti-dsDNA antibodies, or anti-Smith antibody elevated to above normal level.
4. SLEDAI-2K score ≥6 points (Table 8 in Appendix) at index date.
5. No record of current pregnancy at index date.
6. Valid measurement of SDI (Table 9 in Appendix) at index date.

Exclusion Criteria:

Selected key exclusion criteria from the TULIP trials have been adapted to the RW setting and will be applied to patients in the UTLC. Patients who meet any of the following criteria will be excluded from the study:

1. Corticosteroid dose \>40 mg/day (oral prednisone equivalent) at index date.
2. Any record of receiving any biologic agent (e.g., anifrolumab, belimumab, rituximab, abatacept) at index date or within 4 weeks prior to index date.
3. Any record of malignancy at any point prior to index date, except skin malignancy ≥1 year prior to index date.
4. Record of persistent, new or recurrent nephrotic syndrome, chronic dialysis, or renal transplant at index date.
5. Serum creatinine \>2.0 mg/dL (or \>181 μmol/L) at index date.

   The following additional exclusion criteria may be applied to the study cohort at the time of analysis, if it is judged that their application will not significantly reduce the sample size available:
6. Record of alcohol consumption ≥14 units/week at index date or ≤1 year prior to index date

Primary outcomes:
measure: SLICC/ACR damage index (SDI) at week 208
timeFrame: 208 weeks
Secondary outcomes:
measure: SDI at week 208 by organ damage at baseline
timeFrame: 208 weeks
measure: Time to first organ damage progression as measured by SDI.
timeFrame: 208 weeks
measure: Cumulative steroid intake
timeFrame: 208 weeks
measure: Average daily steroid dose
timeFrame: 208 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Zahi Touma, Dr
role: PRINCIPAL_INVESTIGATOR
References: