WEUKBRE5716: Steroid-related Damage in Systemic Lupus Erythematosus (Hopkins)

WEUKBRE5716: Quantifying the Burden of Steroid-related Damage in Systemic Lupus Erythematosus in the Hopkins Lupus Cohort

The study is designed to assess the association between steroid exposure and five potentially steroid-related adverse events within a cohort of individuals with systemic lupus erythematosus (SLE). Study objectives are to quantify the fraction of the risk of new (i) diabetes, (ii) hypertension, (iii) cataracts, (iv) osteoporosis and (v) avascular necrosis that is attributable to cumulative corticosteroid exposure in SLE patients. The study will consist of five matched case-control analyses nested within the Hopkins Lupus Cohort. Cases will be incident SLE cases who have developed one of the case outcomes (diabetes, hypertension, cataracts, osteoporosis with fracture or vertebral collapse or avascular necrosis). Controls will be matched to cases on time since SLE diagnosis. The primary exposures to be assessed are cumulative dose of steroid (g) and cumulative duration of exposure to steroids. The extent of the risk associated with steroids will be explored through modeling of the relationship and through calculation of attributable risks of exposure (number of cases associated with the highest exposure quartile of each primary exposure).

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Cumulative corticosteroid exposure

• Study Type: Observational
• Enrollment (Actual): 1

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Cases and controls will be identified from the Hopkins Lupus Cohort, a prospective longitudinal study of lupus activity, organ damage, and quality of life in patients with SLE which has followed patients up since 1987. The cohort database is continually updated and includes socio-demographic information, medical and reproductive history, comorbidities, SLE complications, and treatment. Data, collected at each patient visit, includes SLE clinical activity indices, laboratory data and treatment (medication and dose).

Description

Inclusion Criteria:

• Newly diagnosed SLE as per ACR criteria
• No history of "case" event of interest in follow-up time prior to SLE diagnosis (case) or during follow-up time since SLE diagnosis that is equivalent to length of case at-risk time period (controls)

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

10

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Incident diabetes cases; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who are newly diagnosed with diabetes during follow-up, subsequent to SLE diagnosis.	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident diabetes controls; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who have no record of diabetes during follow-up time (years) since SLE diagnosis that is equivalent to length of case at-risk time. Controls are matched to cases on decade of SLE diagnosis: 1987-1989, 1990-1999, 2000-2009, 2010+	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident hypertension cases; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who are newly diagnosed with hypertension during follow-up, subsequent to SLE diagnosis.	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident hypertension controls; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who have no record of hypertension during follow-up time (years) since SLE diagnosis that is equivalent to length of case at-risk time. Controls are matched to cases on decade of SLE diagnosis: 1987-1989, 1990-1999, 2000-2009, 2010+	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident cataract cases; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who are newly diagnosed with cataract during follow-up, subsequent to SLE diagnosis.	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident cataract controls; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who have no record of cataract during follow-up time (years) since SLE diagnosis that is equivalent to length of case at-risk time. Controls are matched to cases on decade of SLE diagnosis: 1987-1989, 1990-1999, 2000-2009, 2010+	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident osteoporosis cases; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who are newly diagnosed with osteoporosis during follow-up, subsequent to SLE diagnosis.	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident osteoporosis controls; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who have no record of osteoporosis during follow-up time (years) since SLE diagnosis that is equivalent to length of case at-risk time. Controls are matched to cases on decade of SLE diagnosis: 1987-1989, 1990-1999, 2000-2009, 2010+	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident avascular necrosis cases; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who are newly diagnosed with avascular necrosis during follow-up, subsequent to SLE diagnosis	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.
Incident avascular necrosis controls; Individuals with newly diagnosed SLE selected from the Hopkins Lupus Cohort (1987-2011) who have no record of avascular necrosis during follow-up time (years) since SLE diagnosis that is equivalent to length of case at-risk time. Controls are matched to cases on decade of SLE diagnosis: 1987-1989, 1990-1999, 2000-2009, 2010+	Drug: Cumulative corticosteroid exposure; Cumulative steroid exposure will be modeled as cumulative dose (prednisone equivalent mg), cumulative days of exposure at any dose, cumulative days of exposure to doses ≥7.5mg and cumulative days of exposure to doses ≥20mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New diagnoses of diabetes, hypertension, cataracts, osteoporosis, or avascular necrosis	New diagnoses of diabetes, hypertension, cataracts, osteoporosis, or avascular necrosis recorded after SLE diagnosis in the Hopkins Lupus cohort	Over a period of 25 years from 1987-2011

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Davidson JE, Fu Q, Rao S, Magder LS, Petri M. Quantifying the burden of steroid-related damage in SLE in the Hopkins Lupus Cohort. Lupus Sci Med. 2018 May 14;5(1):e000237. doi: 10.1136/lupus-2017-000237. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: June 7, 2012
• First Submitted That Met QC Criteria: June 7, 2012
• First Posted (Estimate): June 11, 2012

Study Record Updates

• Last Update Posted (Estimate): April 25, 2016
• Last Update Submitted That Met QC Criteria: April 21, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: diabetes; hypertension; systemic lupus erythematosus; osteoporosis; Steroid; cataracts; avascular necrosis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 116015; WEUKBRE5716 (Other Identifier: GSK)