Long-Term Organ Damage: Anifrolumab Versus Real-World Standard of Care in Adult Patients With Active Systemic Lupus Erythematosus (LASER)

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

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).

Study Overview

• Status: Completed
• Conditions: Long-Term Organ Damage in Adult Patients With Active Systemic Lupus Erythematosus

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.

• Study Type: Observational
• Enrollment (Actual): 561

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1L7
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Tulip Trial Group; Patients who initiated 300 mg of anifrolumab in TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway)-1 or -2.
Toronto Lupus Cohort Group; Participants who received RW Standard Of Care for SLE from the University of Toronto Lupus Clinic (UTLC) registry.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SLICC/ACR damage index (SDI) at week 208	Organ Damage measured using the SDI . The SDI is designed to assess irreversible damage across 12 organ systems in SLE patients, independently of cause or attribution.	208 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SDI at week 208 by organ damage at baseline	To estimate the effect of anifrolumab plus SOC in TULIP compared to RW SOC on organ damage accrual as measured by SDI at 208 weeks post-treatment initiation in the following subgroups: patients with no organ damage at baseline, and patients with any organ damage at baseline.	208 weeks
Time to first organ damage progression as measured by SDI.	To estimate effect of anifrolumab plus SOC in TULIP compared to RW SOC on time to first organ damage progression as measured by SDI.	208 weeks
Cumulative steroid intake	To estimate the effect of anifrolumab plus SOC in TULIP compared to RW SOC on cumulative steroid intake (prednisone equivalent) up to 208 weeks post-treatment initiation.	208 weeks
Average daily steroid dose	To estimate the effect of anifrolumab plus SOC in TULIP compared to RW SOC on average daily steroid dose (prednisone equivalent) at 208 weeks post-treatment initiation.	208 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: University Health Network, Toronto; IQVIA Pvt. Ltd
• Investigators: Principal Investigator: Zahi Touma, Dr, University Health Network, Toronto

Publications and helpful links

Helpful Links

• D3461R00077_CSR synopsis_Redacted

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2024
• Primary Completion (Actual): June 24, 2025
• Study Completion (Actual): June 24, 2025

Study Registration Dates

• First Submitted: June 27, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Active Systemic Lupus Erythematosus; Anifrolumab; Long-Term Organ Damage
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: D3461R00077

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No