Prediction of Relapse Risk in Stable Systemic Lupus Erythematosus (PRESS)

Evaluation and Prediction of Relapse Risk After Glucocorticoid Withdrawal in Patients With Stable Systemic Lupus Erythematosus: An Open-labeled Multi-centric Randomized Controlled Study From China

Whether and when systemic lupus erythematosus (SLE) patients with stable disease should withdraw glucocorticoid (GC)? How about the relapse risk? What are the risk factors for disease flare? All the above are unclear. Long-course GC treatment has a lot of side-effects even in a sustaining low dose. The aim of this study is to explore the relapse risk after GC withdrawal in SLE patients with stable disease more than one year and to establish a predictive model for flare risk stratification.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Other: Drug free; Drug: HCQ; Drug: GC+HCQ

Detailed Description

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a relapsing-remitting course. For patients in remission, glucocorticoid (GC) is used to be maintained in a low dose for a long time in fear of disease flare. Long-term GC could bring a lot of side-effects even in a low dose. Whether and when patients with stable disease should withdraw GC? How about the relapse risk? What are the risk factors for disease flare? All the above remain unclear. The aim of this study is to explore the relapse risk after GC withdrawal in SLE patients with stable disease and to establish a predictive model for risk stratification. Meanwhile the investigators aim to testify the effects of hydroxychloroquine in preventing SLE relapse. This study is an open-labeled randomized controlled clinical trial.

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Xinjiang
    • Urumqi, Xinjiang, China, 830001
      • People's Hospital of Xinjiang Uygur Autonomous Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• SLE diagnosis fulfilled the Systemic Lupus International Collaborating Clinic revision of the American College of Rheumatology Classification Criteria for SLE
• Disease stabilized ≥ 1 year
• SELENA-SLEDAI ≤ 3
• Anti-double strand DNA negative by IF measurement and ≤ 200IU/ml by ELISA method
• Complement 3 (C3) ≥ 0.5*lower limit of the normal range, and fluctuation of the C3 is less than 10% within the last year
• 24 hour urine protein ≤ 0.5g
• Prednisone (or equivalent) ≤ 7.5mg/d for more than 6 months
• No use of immunosuppressants including CsA, MMF, CTX, FK506, LEF, MTX in recent 6 months. But hydroxychloroquine (HCQ) is permitted and should be in use
• Never use biologic agents including Rituximab, Belimumab, Epratuzumab and so on
• No severe organ involvement in recent 2 years including lupus encephalosis, diffused alveolar hemorrhage, thrombotic thrombocytopenia purpura, rapid progressive glomerulonephritis, severe thrombocytopenia, severe hemolytic anemia, myocardial involvement, myeleterosis or severe peripheral neuropathy

Exclusion Criteria:

• Active SLE
• In pregnancy or breastfeeding, plan for pregnancy
• Plan or has been on a surgery in recent 6 months
• Current infection
• History of malignancy
• Severe organ dysfunction or other complications
• Unable to follow up
• Inappropriate to be enrolled
• Psoriasis, porphyria, arrhythmia or eye diseases that contradict with HCQ usage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Full withdrawal; Intervention: 'Drug free'.	Other: Drug free; Both Glucocorticoid(GC) and hydroxychloroquine(HCQ) treatment are stopped in stable SLE patients.
Experimental: GC withdrawal; Intervention: 'HCQ' .	Drug: HCQ; Glucocorticoid(GC) treatment is stopped in stable SLE patients. Hydroxychloroquine (HCQ) is kept as 0.2-0.4g/d; Other Names: Hydroxychloroquine
Experimental: No withdrawal; Intervention: 'GC+HCQ' .	Drug: GC+HCQ; Glucocorticoid(GC) is kept no more than 7.5mg/d. Hydroxychloroquine (HCQ) is kept as 0.2-0.4g/d.; Other Names: Glucocorticoid; Hydroxychloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of subjects with mild to moderate Lupus flare evaluated by modified SELENA-SLEDAI flare index (SFI)	The SFI includes three elements: the SELENA-SLEDAI score (range 0 ~105, with 0 indicating inactive disease and ); an assessment of new or worsening disease activity, medication changes, and hospitalizations that not captured with the use of the SLEDAI; and the score on the physician's global-assessment (PGA) visual-analogue scale (range, 0 to 3, 1=mild, 2=moderate, 3=severe); Mild to moderate flare by SFI is defined as appearance of one of the following: a change in SLEDAI>3 points but≤12 points; or new onset/worse of cutaneous/ mucosal injury (discoid, photosensitivity, profundus, cutaneous vasculitis, bullous lupus, Nasopharyngeal ulcers), serositis (pleuritis and/or pericarditis), arthritis, SLE associated fever; or the need to increase prednisone dosage to no more than 0.5 mg/kg/day; or the need to add hydroxychloroquine or NSAIDs with no increase in the dose GC; or an increment of PGA ranges from 1.0 to 2.5.	33 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of subjects with a SELENA-SLEDAI maintaining at <4 points		33 weeks
Mean change in PGA	The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity; A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity	33 weeks
• Percent of subjects with at least one B in any system evaluated with The British Isles Lupus Activity Group (BILAG) scoring system	BILAG includes 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and haematological). A to E scoring is based on the physician's intention to treat: Grade A: treatment requiring any of the following 1) high dose oral glucocorticoids, eg: prednisolone>20mg/day; 2) intravenous pulse glucocorticoids, eg: pulse methylprednisolone ≥ 500 mg；3)systemic immunomodulators (include biologicals, immunoglobulins and plasmapheresis)；4) therapeutic high dose anticoagulation, eg: warfarin INR 3 - 4; Grade B: treatment requiring any of the following treatment:1) low dose oral glucocorticoids, eg: prednisolone ≤ 20mg/day; 2) intramuscular or intra-articular or soft tissue glucocorticoids injection; 3) topical glucocorticoids;4) topical immunomodulators; 5) antimalarials or thalidomide;6) symptomatic therapy; eg: NSAIDs; Grade C: mild disease; Grade D: inactive now but previously affected; Grade E: systems never involved	33 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Xiangya Hospital of Central South University; Shengjing Hospital; Beijing Hospital; People's Hospital of Xinjiang Uygur Autonomous Region; Anhui Provincial Hospital
• Investigators: Principal Investigator: Xuan Zhang, MD, Peking Union Medical College Hospital; Study Chair: Xuan Zhang, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): September 28, 2022
• Study Completion (Actual): September 28, 2022

Study Registration Dates

• First Submitted: June 3, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimate): July 25, 2016

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 30, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Stable; Relapse Risk; Glucocorticoid Withdrawal
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Disease Attributes; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine; Glucocorticoids
• Other Study ID Numbers: ZS-906

Plan for Individual participant data (IPD)

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