Prediction of Relapse Risk in Stable Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Other: Drug free
* Drug: HCQ
* Drug: GC+HCQ


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, Stable, Relapse Risk, Glucocorticoid Withdrawal