***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The presence of renal noninflammatory necrotizing vasculopathy ( NNV ) is often associated with a severe form of lupus nephritis ( LN ) , which is unresponsive to st and ard therapy . We conducted a 6-month r and omized , prospect i ve , open-label trial comparing mycophenolate mofetil ( MMF ) ( 1.5—2.0 g/day ) with monthly i.v . cyclophosphamide ( CTX ) ( 0.75—1.0 g/m2 ) as induction therapy for class IV LN with NNV . The primary and second end points were complete remission ( CR ) and partial remission ( PR ) , respectively . Of 20 patients recruited , nine were r and omly assigned to MMF and 11 to CTX . The baseline characteristics between groups were not significant . CR was achieved in four patients ( 44.4 % ) receiving MMF and in none of the patients receiving CTX ( P = 0.026 ) . PR was achieved in two patients ( 22.2 % ) in the MMF group and three patients ( 27.2 % ) in the CTX group . The total remission rate ( CR + PR ) in the MMF and CTX group was 66.6 and 27.2 % , respectively ( P = 0.17 ) . MMF was more effective than i.v . CTX in reducing proteinuria and haematuria . Adverse events were significantly less frequent with MMF than with CTX ( P = 0.028 ) . MMF was superior to i.v . CTX in inducing CR of LN with NNV and had a more favourable safety profile . Lupus ( 2007 ) 16 , 707—712 Class V lupus nephritis ( LN ) occurs in one-fifth of biopsy-proven cases of systemic lupus erythematosus . To study the effectiveness of treatments in this group of patients , we pooled analysis of two large r and omized controlled multicenter trials of patients with diverse ethnic and racial background who had pure class V disease . These patients received mycophenolate mofetil ( MMF ) or intravenous cyclophosphamide ( IVC ) as induction therapy for 24 weeks , with percentage change in proteinuria and serum creatinine as end points . Weighted mean differences , pooled odds ratios , and confidence intervals were calculated by using a r and om-effects model . A total of 84 patients with class V disease were divided into equal groups , each group had comparable entry variables but one received MMF and one received IVC . Within these groups , 33 patients on MMF and 32 patients on IVC completed 24 weeks of treatment . There were no differences between the groups in mean values for the measured end points . Similarly , no difference was found regarding the number of patients who did not complete the study or who died . In patients with nephrotic syndrome , no difference was noted between those treated with MMF and IVC  regarding partial remission or change in urine protein . Hence we found that the response to MMF as induction treatment of patients with class V LN appears to be no different from that to IVC BACKGROUND Although mycophenolate mofetil ( MMF ) is being increasingly used to manage lupus nephritis ( LN ) , long-term experience is limited . Despite treatment , a significant proportion of patients will be refractory to this regime . METHODS We report , in this observational study , our long-term experience treating 70 patients with biopsy-proven LN , with MMF as continuous induction-maintenance therapy , who were followed up prospect ively over a 5-year period . As rescue therapy for MMF-resistant cases , tacrolimus ( 0.075 mg/kg/day ) was added . The study primary end point was complete response ( CR ) . Secondary end points included partial response ( PR ) , treatment failure , relapse and side effects . Predictor factors associated to renal outcome were analysed by Cox regression analysis . RESULTS Thirty-six  MMF-treated  patients ( 51 % ) remained in CR , and 23 ( 33 % ) failed treatment at last follow-up . Time to treatment failure was associated with persistent hypoalbuminaemia ( hazard ratio ( HR ) = 0.87 ; 95%CI , 0.81 - 0.95 ; P = 0.001 ) , higher proteinuria ( HR = 1.29 ; 95%CI , 1.03 - 1.62 ; P = 0.030 ) and fewer early responses ( HR 0.28 ; 95%CI , 0.10 - 0.77 ; P = 0.014 ) . Renal relapse occurred in 24 ( 34 % ) patients . Time to flare was associated with persistent anti-dsDNA titres ( HR = 1.001 ; 95%CI , 1.001 - 1.003 ; P = 0.005 ) and younger age at inclusion ( HR = 0.36 ; 95%CI , 0.14 - 0.90 ; P = 0.029 ) . Tacrolimus was added to 17 ( 24 % ) patients . A significant reduction of proteinuria was already observed at 3 months ( P = 0.002 ) . After 2 years follow-up , 12 ( 70 % ) of them achieved clinical response ( six CR and six PR ) . Conclusions . MMF is an effective treatment for LN . Combination therapy with tacrolimus is an effective and safe alternative for MMF-resistant patients Background Current method ological guidelines provide advice about the assessment of sub-group analysis within RCTs , but do not specify explicit criteria for assessment . Our objective was to provide research ers with a set of criteria that will facilitate the grading of evidence for moderators , in systematic review s. Method We developed a set of criteria from method ological manuscripts ( n = 18 ) using snowballing technique , and electronic data base search es . Criteria were review ed by an international Delphi panel ( n = 21 ) , comprising authors who have published method ological papers in this area , and research ers who have been active in the study of sub-group analysis in RCTs . We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data . Free responses were coded for consensus and disagreement . In a subsequent round additional criteria were extracted from the Cochrane Review ers ' H and book , and the process was repeated . Results The recommendations are that meta-analysts report both confirmatory and exploratory findings for sub-groups analysis . Confirmatory findings must only come from studies in which a specific theory/ evidence based a-priori statement is made . Exploratory findings may be used to inform future/subsequent trials . However , for inclusion in the meta- analysis of moderators , the following additional criteria should be applied to each study : Baseline factors should be measured prior to r and omisation , measurement of baseline factors should be of adequate reliability and validity , and a specific test of the interaction between baseline factors and interventions must be presented . Conclusions There is consensus from a group of 21 international experts that method ological criteria to assess moderators within systematic review s of RCTs is both timely and necessary . The consensus from the experts result ed in five criteria divided into two groups when synthesis ing evidence : confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research . These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies Background Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis ( LN ) . This investigator-initiated r and omised trial tested whether mycophenolate mofetil ( MMF ) was superior to azathioprine ( AZA ) as maintenance treatment . Methods A total of 105 patients with lupus with proliferative LN were included . All received three daily intravenous pulses of 750 mg methylprednisolone , followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg . Based on r and omisation performed at baseline , AZA ( target dose : 2 mg/kg/day ) or MMF ( target dose : 2 g/day ) was given at week 12 . Analyses were by intent to treat . Time to renal flare was the primary end point . Mean ( SD ) follow-up of the intent-to-treat population was 48 ( 14 ) months . Results The baseline clinical , biological and pathological characteristics of patients allocated to AZA or MMF did not differ . Renal flares were observed in 13 ( 25 % ) AZA-treated and 10 ( 19 % ) MMF-treated patients . Time to renal flare , to severe systemic flare , to benign flare and to renal remission did not statistically differ . Over a 3-year period , 24 h proteinuria , serum creatinine , serum albumin , serum C3 , haemoglobin and global disease activity scores improved similarly in both groups . Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients . Adverse events did not differ between the groups except for haematological cytopenias , which were statistically more frequent in the AZA group ( p=0.03 ) but led only one patient to drop out . Conclusions Fewer renal flares were observed in patients receiving  MMF  but the difference did not reach statistical significance Recent studies have suggested that mycophenolate mofetil ( MMF ) may offer advantages over intravenous cyclophosphamide ( IVC ) for the treatment of lupus nephritis , but these therapies have not been compared in an international r and omized , controlled trial . Here , we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational , two-phase ( induction and maintenance ) study . We r and omly assigned 370 patients with classes III through V lupus nephritis to open-label MMF ( target dosage 3 g/d ) or IVC  ( 0.5 to 1.0 g/m(2 ) in monthly pulses ) in a 24-wk induction study . Both groups received prednisone , tapered from a maximum starting dosage of 60 mg/d . The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine . Secondary end points included complete renal remission , systemic disease activity and damage , and safety . Overall , we did not detect a significantly different response rate between the two groups : 104 ( 56.2 % ) of 185 patients responded to MMF compared with 98 ( 53.0 % ) of 185 to IVC . Secondary end points were also similar between treatment groups . There were nine deaths in the MMF group and five in the IVC group . We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events , serious adverse events , or infections . Although most patients in both treatment groups experienced clinical improvement , the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more In the United States , approximately 35 % of adults with Systemic Lupus Erythematosus ( SLE ) have clinical evidence of nephritis at the time of diagnosis ; with an estimated total of 50–60 % developing nephritis during the first 10 years of disease [ 1–4 ] . The prevalence of nephritis is significantly higher in African Americans and Hispanics than in Caucasians , and is higher in men than in women . Renal damage is more likely to develop in non-Caucasian groups [ 2–4 ] . Overall survival in patients with SLE is approximately 95 % at 5 years after diagnosis and 92 % at 10 years [ 5 , 6 ] . The presence of lupus nephritis significantly reduces survival , to approximately 88 % at 10 years , with even lower survival in African Americans [ 5 , 6 ] . The American College of Rheumatology ( ACR ) last published guidelines for management of systemic lupus erythematosus ( SLE ) in 1999 [ 7 ] . That publication was design ed primarily for education of primary care physicians and recommended therapeutic and management approaches for many manifestations of SLE . Recommendations for management of lupus nephritis ( LN ) consisted of pulse glucocorticoids followed by high dose daily glucocorticoids in addition to an immunosuppressive medication , with cyclophosphamide viewed as the most effective immunosuppressive medication for diffuse proliferative glomerulonephritis . Mycophenolate mofetil was not yet in use for lupus nephritis and was not mentioned . Since that time , many clinical trials of glucocorticoids-plus-immunosuppressive interventions have been published , some of which are high quality prospect i ve trials , and some not only prospect i ve but also r and omized . Thus , the ACR determined that a new set of management recommendations was in order . A combination of extensive literature review and the opinions of highly qualified experts , including rheumatologists , nephrologists and pathologists , has been used to reach the recommendations . The management strategies discussed here apply to lupus nephritis in adults , particularly to those receiving care in the United States of America , and include interventions that were available in the United States as of April 2011 . While these recommendations were developed using rigorous methodology , guidelines do have inherent limitations in informing individual patient care ; hence the selection of the term “ recommendations . ” While they should not supplant clinical judgment or limit clinical judgment , they do provide expert advice to the practicing physician managing 
    Output:
    
There was very low QoE for other moderators or prognostic factors associated with MMF treatment outcomes .