Improving the Assessment of SLE Disease Activity

NCT03144063 | Completed

• 1 other identifier: 15-9195
• Study Type: observational
• Target: 247
• Locations: 1 country
• Sites: 1

Brief Summary

Physicians' assessment of disease activity in SLE is fundamental but challenging. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) is one of the most commonly used disease activity indices. Clinical trials experience suggested that the disease activity instruments did not function well on their own, and composite measures were developed to address this issue. This approach has been adopted after learning from clinical trials that the absence of a robust sensitive index is a major flaw when designing a trial. Another issue with clinical trials is the confounding effect of corticosteroids, which to date have been the most effective treatment for the management of lupus. However, unregulated use of corticosteroids in drug trials decrease the investigator's ability to differentiate between the tested drugs and placebo as they appear to enhance response among the placebo arm and thus mask the effect of the tested drug. In this study, the aim is to develop and validate a new index, SLEDAI-2K Glucocorticosteroid Index (SLEDAI-2KG). It is very challenging to evaluate improvement in drug trials in the context of the standard of care treatment which includes corticosteroids. This novel index, SLEDAI-2KG, will help to overcome the confounding effect of corticosteroids and to allow for more accurate description of disease improvement and thus facilitate accurate investigations of new therapeutic agents.

Conditions

Lupus Erythematosus, Systemic; SLE

Keywords

Disease Activity; SLEDAI-2K

Outcome Measures

Primary Outcomes (4)

• Objective I - Initial Development and Validation of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG)

  The new index SLEDAI-2KG will be validated against the old index Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) in the TLC cohort. Improved patients (responders) will be identified based on SLEDAI-2K definition of improvement (decrease in the total score by ≥4). Clinician scoring on a Likert scale (external construct) for disease activity - Improvement based on predefined definitions

  3 months

• Objective II - Further validation of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG) using BLISS trial data

  SLEDAI-2KG will be further validated using BLISS-52 and BLISS-7S trial data on all patients that were enrolled. The primary endpoint in both trials was SLE Responder Index (SRI). The SRI incorporates the Safety of Estrogens in Lupus Erythematosus-National Assessment-SLEDAI (SELENA-SLEDAI), British Isles Lupus Assessment Group (BILAG), and Physician Global Assessment (PGA). The primary outcome of this objective is the SRI-modified: The SRI-modified will include the 2nd and 3rd components of SRI, but replace the SELENA-SLEDAI with the SLEDAI-2KG.

  5 months

• Objective IIIA - Assessment of concurrent construct validity of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG) prospectively in the University of Toronto Lupus Clinic

  Improved patients (responders) will be identified based on Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) definition of improvement (decrease in the total score by ≥4).

  8 months

• Objective IIIB - Identification of Systemic Lupus Erythematosus Disease Activity Index-2000 Glucocorticosteroid (SLEDAI-2KG) Responders

  SLEDAI-2KG improved patients (responders) will be identified based on the definition of improvement (decrease in the total score by ≥4).

  8 months

Study Arms (3)

Toronto Lupus Cohort

Objective 1 and 3 Cohort: * ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy * Clinician's diagnosis based on his/her assessment * Patients from the Toronto Lupus Clinic with regular follow-up, defined as having follow up visits at 3 and 6 months from the baseline visit (1st study visit).

BLISS-52 Cohort

Objective 2 Cohort: Validation of the SLEDAI-2KG will be completed on BLISS-52 trial data. The extracted trial data consists of data on all patients that participated in the trial.

BLISS-76 Cohort

Objective 2 Cohort: Validation of the SLEDAI-2KG will be completed on BLISS-76 trial data. The extracted trial data consists of data on all patients that participated in the trial.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Objective I Initial Development and Validation of SLEDAI-2KG This is a retrospective validation study of SLEDAI-2KG using the University of Toronto Lupus Clinic (TLC) database. Clinical and laboratory data is collected according to a standard protocol at regular intervals (2 to 6 months between visits) and stored on a computer database. Objective II Further retrospective validation of SLEDAI-2KG using BLISS trial data. All patients in GSK BLISS-52 (N=865) and BLISS-76 (N=819) were assessed at regular intervals and data including clinical and laboratory features of SLE, medications and in particular corticosteroids was collected and will be used in the validation of SLEDAI-2KG. Objective III Assessment of concurrent construct validity of SLEDAI-2KG prospectively in the TLC Cohort Patients from the TLC with active disease with a flare (increase in SLEDAI-2K by at least 4) that requires an increase in the dose of prednisone to ≥15 mg/day or initiation of prednisone at ≥15 mg/day.

You may qualify if:

• Objective I:
• ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy
• Clinician's diagnosis based on his/her assessment
• Patients from the Toronto Lupus Clinic with regular follow-up, defined as having follow up visits at 3 and 6 months from the baseline visit (1st study visit).
• Objective II:
• Participant in the BLISS-52 and BLISS-76 trials
• Objective III:
• ≥4 American College of Rheumatology (ACR) criteria or 3 ACR criteria plus a typical histological lesion of SLE on renal or skin biopsy
• Increase in SLEDAI-2K ≥4
• Clinician's diagnosis based on his/her assessment

You may not qualify if:

• Objective I and III:
• Patients with missing follow up visits at 3 and 6 months from the baseline visit (1st study visit).
• Patients with missing data in the charts for all visits.
• Objective II:
• Participants who did not complete the trial and therefore have missing data points for primary endpoint measures

Sponsors & Collaborators

• University Health Network, Toronto: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M4L2P5, Canada

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Zahi Touma, MD PhD

  University Health Network and University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 8, 2017
• Study Start: July 11, 2017
• Primary Completion: June 4, 2020
• Study Completion: June 4, 2020
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)