Optimization of Glucocorticoid Taper Strategies for SLE-ITP

Lupus Erythematosus, Systemic Clinical Trial

Official title:

Optimization of Glucocorticoid Taper Strategies for Maintenance Therapy of Systemic Lupus Erythematosus Associated Immune Thrombocytopenia (SLE-ITP)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05506033
• Other study ID #: tanklhj@163.com
• Status: Enrolling by invitation
• Phase: N/A
• Start date: August 15, 2022
• Est. completion date: December 1, 2025

Study information

• Verified date: July 2022
• Source: Fujian Medical University Union Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SLE associated immune thrombocytopenia (SLE-ITP) is one of the main clinical manifestations of SLE. Approximately 70% of SLE patients follow a relapsing-remitting course. Similarly, SLE-ITP often relapses during GCs tapering. At the same time, patients with SLE-ITP may suffer from thrombocytopenia and damage to vital organs when they relapse, seriously affecting their lives. Therefore, maintenance therapy after remission is an inevitable choice for SLE-ITP.

The SLE guidelines recommend GCs and immunosuppressive agents(ISA) are first-line maintenance treatment in the treatment of SLE-ITP. GCs is indispensable in SLE treatment, but it is associated with a series of side effects, which are related to the dosage and duration of use. How to maintain remission with the most appropriate dose of GCs is a problem that needs to be considered in clinical practice. However, the existing guidelines lack detailed recommendations on the specific use of GCs in maintenance therapy for SLE-ITP, and there is also a lack of relevant clinical studies to guide. The GCs reduction regimen commonly used in maintenance therapy is a gradual reduction after 1 month of adequate GCs therapy, usually by 10% of the original dose every 2 weeks. However, the side effects of this reduction method are obvious, and whether the treatment can be maintained with less cumulative dose and maintenance duration of GCs is an urgent problem to be solved.

Clinical observations show that in a small number of patients with relative contraindications to GCs, a more rapid taper can maintain an effective response. Currently, rapid dosing reduction is recommended in both Lupus nephritis(LN) and the ANCA-associated nephritis guidelines of ACR. However, SLE-ITP changes more rapidly than LN. Although similar maintenance responses have been observed in a few patients between rapid dosing reduction and conventional method, relevant clinical studies are lacking. It is necessary to explore the effectiveness of rapid GCs tapering method.

Therefore, the investigators plan to conduct a single-center, prospective, randomized design, non-blind, non-inferiority controlled study on the optimization of GCs taper strategy for SLE-ITP maintenance therapy.In this study,sustained response rate and relapse rate within 3 months and 6 months were observed to judge the effectiveness of rapid GCs taper strategy, thus providing a basis for clinical GCs taper strategy.

Description:

Complete response was defined as a platelet count ≥100x10^9/L and the absence of bleeding and new other symptoms.Complete response would be confirmed by platelet counts on 2 separate occasions 7 days apart. Adequate glucocorticoids treatment was defined as at least a dose 50mg/day of prednisone (or equivalent glucocorticoids) for patients with weight less than 50kg, 60mg/day for patients with weight 50-75kg , 75mg/day for patients with weight more than 75kg. Adequate glucocorticoids were used for induction, and the total duration of adequate glucocorticoids treatment for patients enrolled was no longer than 3 weeks.Neither Thrombopoietin receptor agonist(TPO-RA) nor intravenous immunoglobulin(IVIG)were permitted in induction therapy or maintenance therapy.In addition to hydroxychloroquine(HCQ), other immunosuppressive agents are not permitted in induction therapy or maintenance therapy. After confirmation of complete response, the patients enrolled were randomly divided into two groups according to two different methods of GCs taper.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 120
• Est. completion date: December 1, 2025
• Est. primary completion date: August 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Men and women aged 14-75 (including 14 and 75);

2. It meets the 2012 Systemic lupus Erythematosus International Collaborative Group (SLICC) classification criteria or the 2019 ACR and European Society of Rheumatology (EULAR) classification criteria ;

3. severe SLE-ITP patients with PLT=30x10^9/L at onset and complete response (PLT =100x10^9/L) after induction therapy within 3 weeks;

4. Prior to the commencement of any study-specific procedure, the patient or legal representative must provide signed and dated written informed consent.

Exclusion Criteria:

1. Relapse in the presence of glucocorticoid and/or immunosuppressive maintenance therapy;

2. Combined with antiphospholipid syndrome;

3. Combined with other important organ damage such as lupus nephritis, neuropsychiatric lupus;

4. Coexisting immune diseases require glucocorticoid and/or immunosuppressive therapy;

5. There are serious comorbidities affecting treatment such as diabetes, severe hypertension, coronary heart disease;

6. self-evaluation affected by poor understanding ability, vision decline and other reasons ;

7. Poor adherence and failure to adhere to treatment as prescribed. -

Related Conditions & MeSH terms

• Glucocorticoids
• Lupus Erythematosus, Systemic
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Procedure:
• rapid GCs taper
After a complete response was achieved, the GCs dose was halved from the original dose.

Locations

Country	Name	City	State
China	Fujian Medical University Union Hospital	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Medical University Union Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

Chinese Rheumatology Association; National Clinical Research Center for Dermatologic and Immunologic Diseases; Chinese Systemic Lupus Erythematosus Treatment and Research Group. [2020 Chinese guidelines for the diagnosis and treatment of systemic lupus er — View Citation

Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, Archer AM, Conn DL, Full KA, Grayson PC, Ibarra MF, Imundo LF, Kim S, Merkel PA, Rhee RL, Seo P, Stone JH, Sule S, Sundel RP, Vitobaldi OI, Warner A, Byram K, Dua AB, Husainat N, James KE, Kalot MA, Lin YC, Springer JM, Turgunbaev M, Villa-Forte A, Turner AS, Mustafa RA. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2021 Aug;73(8):1366-1383. doi: 10.1002/art.41773. Epub 2021 Jul 8. — View Citation

Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, Cervera R, Doria A, Gordon C, Govoni M, Houssiau F, Jayne D, Kouloumas M, Kuhn A, Larsen JL, Lerstrøm K, Moroni G, Mosca M, Schneider M, Smolen JS, Svenungsson E, Tesar V, Tincani A, Troldborg A, van Vollenhoven R, Wenzel J, Bertsias G, Boumpas DT. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019 Jun;78(6):736-745. doi: 10.1136/annrheumdis-2019-215089. Epub 2019 Mar 29. — View Citation

Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT. Update ?n the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis. 2021 Jan;80(1):14-25. doi: 10.1136/annrheumdis-2020-218272. Epub 2020 Oct 13. Review. — View Citation

Jung JH, Soh MS, Ahn YH, Um YJ, Jung JY, Suh CH, Kim HA. Thrombocytopenia in Systemic Lupus Erythematosus: Clinical Manifestations, Treatment, and Prognosis in 230 Patients. Medicine (Baltimore). 2016 Feb;95(6):e2818. doi: 10.1097/MD.0000000000002818. — View Citation

Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	significant relapse	significant relapse were defined as 1 or more of the following: 1)a platelet count<30x10^9/L or less than 2-fold increase of the baseline platelet count or bleeding;2)new damage to important organs(renal, central nervous system, cardiopulmonary, vasculitis, myositis,fever, active hemolytic anemia or gastrointestinal activity);3)manifestations requiring an increase in prednisone(or equivalent) to >0.5mg/kg/day;4)SLEDAI-2K instrument score greater than 12;5) change in physician's global assessment score from baseline to greater than 2.5.	within 12 weeks
Primary	significant relapse	significant relapse were defined as 1 or more of the following: 1)a platelet count<30x10^9/L or less than 2-fold increase of the baseline platelet count or bleeding;2)new damage to important organs(renal, central nervous system, cardiopulmonary, vasculitis, myositis,fever, active hemolytic anemia or gastrointestinal activity);3)manifestations requiring an increase in prednisone(or equivalent) to >0.5mg/kg/day;4)SLEDAI-2K instrument score greater than 12;5) change in physician's global assessment score from baseline to greater than 2.5.	within 24 weeks
Secondary	Mild to moderate relapse	Mild to moderate relapse were defined as 1 or more of the following: 1)30x10^9/L= a platelet count <100x10^9/L and at least 2-fold increase of the baseline count and absence of bleeding and new damage to important organs(renal, central nervous system, cardiopulmonary, vasculitis, fever, active hemolytic anemia or gastrointestinal activity);2)any manifestations requiring an increase in prednisone(or equivalent) not greater than 0.5mg/kg/day;3)greater than 3-point change in SLEDAI-2K instrument score, with total score of 12 or less;4)or change in the physician's global assessment score of 1.0 or more but remaining 2.5 or less.	within 12 weeks
Secondary	Mild to moderate relapse	Mild to moderate relapse were defined as 1 or more of the following: 1)30x10^9/L= a platelet count <100x10^9/L and at least 2-fold increase of the baseline count and absence of bleeding and new damage to important organs(renal, central nervous system, cardiopulmonary, vasculitis, fever, active hemolytic anemia or gastrointestinal activity);2)any manifestations requiring an increase in prednisone(or equivalent) not greater than 0.5mg/kg/day;3)greater than 3-point change in SLEDAI-2K instrument score, with total score of 12 or less;4)or change in the physician's global assessment score of 1.0 or more but remaining 2.5 or less.	within 24 weeks
Secondary	Clinical remission	According to DORIS's definition of SLE remission in 2021.	at 24 weeks
Secondary	a Lupus Low Disease Activity State	According to the definition of SLE low disease activity state formulated in 2015.	at 24 weeks