***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: OBJECTIVE To assess the potential benefits of methotrexate in patients with systemic lupus erythematosus ( SLE ) . METHODS A 12-month , double-blind , placebo-controlled trial of methotrexate with folic acid was conducted . Intent-to-treat analyses were performed with mixed linear models and alpha = 0.04 ( 96 % confidence interval [ 96 % CI ] ) to account for interim analysis of longitudinal data to assess the treatment effects on lupus disease activity and daily steroid dose across monthly measurements , and to test if the treatment effects depended on selected participant characteristics . RESULTS Of 215 participants screened , 94 were excluded , 35 declined , and 86 were r and omized ( methotrexate = 41 , placebo = 45 ) . The groups were balanced for demographic and disease characteristics . Antimalarial use was more frequent in the placebo group , which was adjusted for in multivariable analyses . Sixty participants ( 27 methotrexate , 33 placebo ) completed the study and 26 terminated early . Among participants who had the same baseline prednisone dose , those taking methotrexate received , on average , 1.33 mg/day less prednisone during the trial period ( 96 % CI 0.06 , 2.72 mg/day ; a 22 % reduction of their average-during-trial daily dose ) compared with those in the placebo group . For the primary measure of disease activity ( revised Systemic Lupus Activity Measure ) , methotrexate use was also associated with a marginally significant reduction in the mean during-trial score of 0.86 units ( 96 % CI 0.01 , 1.71 ; P = 0.039 ) . A significant interaction between treatment and baseline damage was found ( P = 0.001 ) . CONCLUSION Methotrexate conferred a significant advantage in participants with moderately active lupus by lowering daily prednisone dose and slightly decreasing lupus disease activity . As a therapeutic option in moderate SLE , methotrexate can be considered to be steroid sparing Aim : The optimal maintenance therapy for active diffuse lupus nephritis remains to be established . In this study , we explored the efficacy and safety of tacrolimus for maintaining remission of active lupus nephritis compared to that of azathioprine . Methods : Seventy patients with biopsy-proven lupus nephritis who achieved remission were enrolled in nine nephrology centers in China from 2006 to 2008 . Patients were r and omized either to tacrolimus plus prednisone ( n = 34 ) or azathioprine plus prednisone ( n = 36 ) for six months . Tacrolimus was titrated to achieve a trough blood concentration of 4–6 ng/mL , and the dosage of azathioprine was 2 mg/kg/d . Prednisone was administered at a dose of 10 mg/d to both groups . The primary outcome was incidence of relapse . Response , clinical parameters and adverse effects were secondary endpoints . Results : After six months of therapy , two of the azathioprine-treated patients developed renal relapse compared to none of the tacrolimus-treated patients ( p = 0.49 ; odds ratio , 1.06 ; 95 % CI ( 0.98 , 1.15 ) ) . Leucopenia ( defined as < 2000 cells per cubic millimeter ) was significantly more frequent in the azathioprine group than the tacrolimus group ( 47 % vs. 9 % , p < .001 ) . Conclusion : In conjunction with prednisone , maintenance therapy with tacrolimus and azathioprine has a similar low rate of renal relapse , and the tacrolimus regimen has a more favorable safety profile , with less leucopenia . However , since our study lacked sufficient power , longer follow-up is needed to draw final conclusions OBJECTIVE B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus ( SLE ) , and rituximab induces depletion of B cells . The Exploratory Phase II/III SLE Evaluation of Rituximab ( EXPLORER ) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE . METHODS Patients entered with > or=1 British Isles Lupus Assessment Group ( BILAG ) A score or > or=2 BILAG B scores despite background immunosuppressant therapy , which was continued during the trial . Prednisone was added and subsequently tapered . Patients were r and omized at a ratio of 2:1 to receive rituximab ( 1,000 mg ) or placebo on days 1 , 15 , 168 , and 182 . RESULTS In the intent-to-treat analysis of 257 patients , background treatment was evenly distributed among azathioprine , mycophenolate mofetil , and methotrexate . Fifty-three percent of the patients had > or=1 BILAG A score at entry , and 57 % of the patients were categorized as being steroid dependent . No differences were observed between placebo and rituximab in the primary and secondary efficacy end points , including the BILAG-defined response , in terms of both area under the curve and l and mark analyses . A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups . Safety and tolerability were similar in patients receiving placebo and those receiving rituximab . CONCLUSION The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse . No differences were noted between placebo and rituximab in the primary and secondary end points . Further evaluation of patient subsets , biomarkers , and exploratory outcome models may improve the design of future SLE clinical trials BACKGROUND Intravenous cyclophosphamide with prednisone is an effective treatment for lupus nephritis , but with significant toxicities . We compared the efficacy and safety of tacrolimus versus intravenous cyclophosphamide as induction therapy . STUDY DESIGN Multicenter noninferiority r and omized controlled trial . SETTING & PARTICIPANTS 81 patients with biopsy-proven lupus nephritis from 9 nephrology centers in China from 2006 - 2008 . INTERVENTION Prednisone and either tacrolimus ( n = 42 ) or intravenous cyclophosphamide ( n = 39 ) for 6 months . Tacrolimus was started at 0.05 mg/kg/d and titrated to achieve a trough blood concentration of 5 - 10 ng/mL. Intravenous cyclophosphamide was initiated at 750 mg/m² of body surface area , then adjusted to 500 - 1,000 mg/m² every 4 weeks for a total of 6 pulse treatments . OUTCOMES & MEASUREMENTS The primary outcome was complete remission ( proteinuria with protein excretion < 0.3 g/24 h , serum albumin ≥3.5 g/dL , normal urinary sediment , and normal or stable serum creatinine level ) at 6 months . Response ( complete or partial remission ) , clinical parameters , and adverse effects were secondary end points . RESULTS After the 6-month induction therapy , the tacrolimus group achieved higher cumulative probabilities of complete remission and response ( 52.4 % vs 38.5 % and 90.5 % vs 82.1 % , respectively ) than the intravenous cyclophosphamide group , but differences were not statistically significant ( log-rank test , P = 0.2 and P = 0.7 , respectively ) . Proteinuria [ corrected ] was significantly decreased in tacrolimus- versus intravenous cyclophosphamide-treated patients after the first month of treatment , even with adjustment for baseline proteinuria ( protein excretion , 1.76 vs 2.40 g/d ; P = 0.02 for the log-transformed analysis ) . [ corrected ] After treatment , serum creatinine levels and estimated glomerular filtration rates were not significantly different between treatment groups . Adverse effects , such as leukopenia and gastrointestinal symptoms , were less frequent in the tacrolimus group . LIMITATIONS Nonblinded , small sample size , and short duration of follow-up . CONCLUSIONS In conjunction with prednisone , induction therapy with tacrolimus is at least as efficacious as intravenous cyclophosphamide and prednisone in producing complete remission of lupus nephritis and has a more favorable safety profile BACKGROUND Severe neurological involvement in systemic lupus erythematosus ( NPSLE ) is one of the most dreadful complications of the disease . OBJECTIVE To identify the best drug , dose , and treatment . PATIENTS AND METHODS The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria , with incident ( no more than 15 days ) onset of severe NP manifestations such as seizures , optic neuritis , peripheral or cranial neuropathy , coma , brainstem disease , or transverse myelitis . Induction treatment with 3 g of IV methylprednisolone ( MP ) followed by either IV monthly cyclophosphamide ( Cy ) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year . The primary end point was response to treatment : at least 20 % improvement from basal conditions on clinical , laboratory , or specific neurological testing variables . RESULTS Overall , a response rate of 75 % was observed . Of the 32 patients studied , 18/19 receiving Cy and 7/13 receiving MP responded to treatment ( p<0.03 ) . CONCLUSIONS Cy seems to be more effective than MP in the treatment of acute , severe NPSLE Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis . In this prospect i ve study , 40 patients with class V+IV lupus nephritis were r and omly assigned to induction therapy with  mycophenolate mofetil , tacrolimus , and steroids ( multitarget therapy ) or intravenous cyclophosphamide ( IVCY ) . Patients were treated for 6 mo unless complete remission was not achieved , in which case treatment was extended to 9 mo . An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo ( 50 and 65 % , respectively ) than with IVCY ( 5 and 15 % , respectively ) . At 6 mo , eight ( 40 % ) patients in each group experienced partial remission , and at 9 mo , six ( 30 % ) patients receiving multitarget therapy and eight ( 40 % ) patients receiving IVCY experienced partial remission . There were no deaths during this study . Most adverse events were less frequent in the multitarget therapy group . Calcineurin inhibitor nephrotoxicity was not observed , but three patients developed new-onset hypertension with multitarget therapy . In conclusion , multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated Pulse cyclophosphamide is more effective than prednisone alone in preventing  renal failure in lupus nephritis . We undertook a r and omised , controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis , and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations . 65 patients ( 60 female , 5 male ; median [ range ] age 29 [ 10 - 48 ] years ) with severe lupus nephritis were assigned r and omly to monthly pulse methylprednisolone for 6 months ( 25 patients ) , monthly pulse cyclophosphamide for 6 months ( 20 ) , or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years ( 20 ) . Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide ( p less than 0.04 ) . Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide . However , patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide ( p less than 0.01 ) . An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis . Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations 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 , 
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However , compared with cyclophosphamide , azathioprine ( OR 3.04 , 95 % CI ( 1.44 to 6.42 ) ) and cyclosporine ( OR 3.28 , 95 % CI ( 1.04 to 10.35 ) ) were significantly less safety in AE-related withdrawals , and GC was ranked lowest and led to higher withdrawal rates .
Tacrolimus ( TAC ) was ranked high and showed a benefit in many outcomes .
Biologicals and chloroquine also showed good safety in all of the available outcomes , while the beneficial effects of other immunosuppressive drugs were not substantial in different types of serious adverse events .
Conclusions TAC is the safest strategy for patients with SLE .
Biologicals and chloroquine are also fairly safe for patients with SLE .