trial of belimumab combined with multi-target induction therapy in lupus nephritis

Conditions: Lupus Nephritis; Remission; Safety Issues

Summary: the goal of this single-center, prospective clinical trial is to test the safety and efficacy of belimumab combined with multi-target therapy in the treatment of severe lupus nephritis. the main questions it aims to answer are: lupus nephritis complete remission rate at week 24, and the partial remission rate and safety assessments. patients with severe lupus nephritis will be enrolled and received pulse methylprednisolone at a dose of 1.5 to 3.0g, followed by intravenous belimumab at a dose of 10mg per kilogram at weeks 2, 4, and 6, and every 4 weeks thereafter. multitarget therapy will be also administered during the induction phase. induction therapy will last for 24 weeks. patients with severe lupus nephritis who only received multi-target therapy during the same period will be enrolled as the control group.


Eligibility criteria:
inclusion criteria: * active ln in accordance with the american college of rheumatology (acr) diagnostic criteria for sle (1997), sle-dai\>10 points (except type ⅴ ln). * patients with active lupus nephritis (type ⅲ, ⅳ, ⅴ, ⅴ+ⅲ, ⅴ+ⅳ) diagnosed by light microscopy, immunofluorescence microscopy, and electron microscopy according to the isn/rps2003 lupus nephritis classification criteria, with pathological chronicity index (ci) less than 3 points and no tma like changes in interstitial vessels. * proteinuria ≥1.5g/24h, with or without active urinary sediment (urinary sediment red blood cell count \>100/ul, or white blood cell count \>5 /hp, or red blood cell cast, excluding urinary tract infection). * serum creatinine \<3.0mg/dl or egfr\<30 ml/min/1.73m\^2 (ckd-epi formula). * received methylprednisolone pulse therapy within 2 weeks before enrollment, cumulative dose 1.5-3.0g). exclusion criteria: * required renal replacement therapy or received renal replacement therapy within 3 months. * abnormal liver function with elevated alt, ast or bilirubin more than 2 times the upper limit of normal. * abnormal glucose metabolism, defined as fasting blood glucose concentration ≥7.0mmol/l and/or 2-hour postprandial blood glucose concentration \>11.1mmol/l. * mycophenolate mofetil, cyclophosphamide, tacrolimus, cyclosporine a, and high-dose intravenous immunoglobulin (ivig) were used in the past 12 weeks; it did not include oral hormones, azathioprine or tripterygium wilfordii polyglycosides, or intravenous low-dose mp (less than 80mg/ day), or short-term use of cyclosporine a\<2 weeks, or leflunomide \<4 weeks. * known allergy to or contraindication to mmf, tacrolimus, or belimumab; patients with active infection or intravenous antibiotic use within 1 month before admission. * current or past 3 months: active hepatitis b, hepatitis c, tuberculosis, cytomegalovirus pneumonia, active fungal infection, syphilis infection or hiv infection, etc.; active peptic ulcer; a history of drug use and alcohol abuse; severe malnutrition (bmi\<16 kg/m\^2). * other active diseases, such as severe life-threatening cardiovascular diseases; chronic obstructive pulmonary disease, or asthma requiring treatment with oral steroids; bone marrow suppression caused by sle activity was excluded: wbc\<3000/ul, absolute neutrophil count \<1300/ul, and platelet count \< 50 000/ul. patients with active sle who received double plasma filtration, plasma exchange or high-dose gamma globulin therapy within 4 weeks. * patients with malignant hypertension. * women who have fertility requirements, refuse contraception or are lactating. * other investigators considered that they were not suitable for enrollment and may have rapid disease progression or severe disease complications.

Keywords: lupus nephritis b cell depletion therapy remission