Telitacicept Followed With Rituximab Therapy on APS Secondary to SLE

Study Overview
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Brief Summary
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The aim of this study was to observe the clinical efficacy and safety of rituximab (RTX) combination with telitacicept (TA) in patients of systemic lupus erythematosus secondary antiphospholipid syndrome (APS).

Detailed Description
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In this multicenter, prospective, observational study, 80 patients with SLE Secondary APS patients were enrolled. RTX alone or its continuation with TA was observed for 24weeks，and extended for another 24 weeks. At week 12, the RTX group could be converted to the combination group. The primary end point was the response rate of total antiphospholipid antibody (aPL) at week 12. The secondary end points included the decline rate and value of aPL antibody, aGAPSS score, remission degree of specific clinical indicators, changes in SLE disease activity in SAPS group, and drug safety at week 12 and week 24.

Official Title
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The Clinical Efficacy and Safety of Telitacicept Followed With Rituximab Therapy on APS Secondary to SLE ，a Multicentre Observational Study

Conditions
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Antiphospholipid Syndrome

Intervention / Treatment
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* Drug: Telitacicept
* Drug: Rituximab
* Drug: Aspirin
* Drug: Warfarin
* Drug: Hydroxychloroquine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Patients who meet 2006 Sapporo classification criteria of APS or 2020 nonstandard APS performance； 2.Patients who meet 1997 or 2019 SLE classification criteria ; 3.Positive LA /ACL/ aβ2GPI ,on two or more occasions, at least 12 weeks apart; 4.with at least one extra-criteria manifestations of APS, including thrombocytopenia, hemolytic anemia, nephropathy, valve heart disease ,skin ulcer and arterial or deep vein thrombosis; 5.Maintain a stable base treatment regimen for at least 4 weeks before screening; Basic treatment includes anticoagulants/antiplatelet agents, glucocorticoids, and hydroxychloroquine; 6.No response, intolerance or dependence on glucocorticoids and immunosuppressants; 7.Patients who had previously used beliumab or Telitacicept could be enrolled in the study after 12 weeks of discontinuation; 8.Age ≥18 years; 9.Signed Informed consent. Exclusion Criteria: 1.Patients with other causes of thrombocytopenia, hemolytic anemia, valvular heart disease, kidney disease and skin ulcer symptoms were excluded, such as drugs, infections, blood system diseases, genetic metabolic diseases, etc; 2.Severe cardiovascular diseases, kidney, liver and other important organ injuries, serious blood and endocrine system lesions (aplastic anemia, hyperthyroidism crisis, etc.) were excluded; A history of active malignancy (within 5 years) was excluded and chemoradiotherapy was performed; Patients with organ or bone marrow transplantation in the past year were excluded. Exclusion of mentally ill persons; 3.A history of allergy to the relevant test drug; 4.Patients had recently received a live vaccine or planned to use any live vaccine during the study; 5.Ongoing pregnancy; 6.Patients who were participants in clinical trials of other immunosuppressive agents/biologics within 24 weeks; 7.Other conditions that the investigator considers would make the candidate unsuitable for the study;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RTX+TA group<br>Screening stage：Patients received 200mg of rituximab intravenously at week 0 and week 2. Follow-up period：Telitacicept 160mg once a week for 24 weeks Basic treatment： Hydroxychloroquine、Prednisone、Warfarin、Aspirin | Drug: Telitacicept<br>* 160mg once a week for 24 weeks<br>* Other names: TA;Drug: Rituximab<br>* Patients received 200mg of rituximab intravenously at week 0 and week 2.<br>* Other names: RTX;Drug: Aspirin<br>* 50-100mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Asp;Drug: Warfarin<br>* Warfarin should be used in patients with arterial thrombosis, and rivaroxaban should be replaced if the patient cannot reach the standard or cannot tolerate it<br>* Other names: WF;Drug: Hydroxychloroquine<br>* 200mg, po, twice per day (Bid) prescribed，if tolerated by the patient， the dose should remain constant during the observation period<br>* Other names: HCQ;Drug: Prednisone<br>* 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Pred;|
| RTX group<br>Screening stage：Patients received 200mg of rituximab intravenously at week 0 and week 2. Follow-up period Basic treatment：Hydroxychloroquine、Prednisone、Warfarin、Aspirin | Drug: Rituximab<br>* Patients received 200mg of rituximab intravenously at week 0 and week 2.<br>* Other names: RTX;Drug: Aspirin<br>* 50-100mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Asp;Drug: Warfarin<br>* Warfarin should be used in patients with arterial thrombosis, and rivaroxaban should be replaced if the patient cannot reach the standard or cannot tolerate it<br>* Other names: WF;Drug: Hydroxychloroquine<br>* 200mg, po, twice per day (Bid) prescribed，if tolerated by the patient， the dose should remain constant during the observation period<br>* Other names: HCQ;Drug: Prednisone<br>* 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Pred;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who achieved response(complete response and partial response) in aPL profiles | For the lupus anticoagulant (LAC) test, we defined complete response (CR) as a negative test result and no response(NR) as a positive test result； For the anticardiolipin antibody (aCL)/anti-β2 glycoprotein I (anti-β2GPI)enzyme-linked immunosorbent assay,CR was defined as a titer of<the 95th percentile, partial response (PR) was defined as a titer of 95th -99th , and NR was defined as a titer of >the 99th percentile. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who achieved response(complete response and partial response) in aPL profiles | For the lupus anticoagulant (LAC) test, we defined complete response (CR) as a negative test result and no response(NR) as a positive test result； For the anticardiolipin antibody (aCL)/anti-β2 glycoprotein I (anti-β2GPI)enzyme-linked immunosorbent assay,CR was defined as a titer of<the 95th percentile, partial response (PR) was defined as a titer of 95th -99th , and NR was defined as a titer of >the 99th percentile. | Week 24,48 | 
| The change of aPL titer | titer change of lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein-I antibody | week 12 , 24,48 | 
| The changes of the positive number of 7 aPL indicators | Change in the number of antibody positives. | week 12, 24,48 | 
| The change of clinical efficacy in subgroups with different symptoms | Thrombocytopenia, haemolytic anemia, nephropathy, heart valve lesions, skin changes (livedo reticularis, leg ulcers) | Before the screening,baseline and week 12,24,48 | 
| The change of aGAPSS score | The aGAPSS was calculated by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-β2 glycoprotein-I antibodies and four for positive lupus anticoagulant test. | Before the screening,baseline and week 12,24,48 | 
| The change of Damage Index for Antiphospholipid Syndrome (DIAPS) | The score is obtained by adding the output rating for each domain. The instrument demonstrated content, criterion, and construct validity being a precise tool to quantify organ damage in APS. | Before the screening and week 12,24,48 | 
| The change of Physician Global Assessment (PGA) score . | PGA is a physician-reported visual analogue scale that provides an overall meas- ure of the subject's current disease activity,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; | Before the screening,baseline and week 12,24,48 | 
| The change of Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) Score | The SLEDAI-2K is an established, validated SLE activity index. It is based on the presence of 24 features in 9 organ systems and measures disease activity in SLE patients in the previous 10 days. | Before the screening,baseline and week 12,24,48 | 
| The percentage of patients with Lupus Low Disease Activity State (LLDAS) | LLDAS is defined as: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. | Before the screening,baseline and week 12,24,48 | 
| Glucocorticoid (GC) dose and reduction rate | The proportion of patients who received the GC dose at each time point | Before the screening,baseline and week 4,12,24,48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Telitacicept, Rituximab