***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 
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    ***EXAMPLES*** 
    Input: Rituximab ( RTX ) is non-inferior to cyclophosphamide ( CYC ) followed by azathioprine ( AZA ) for remission-induction in severe ANCA-associated vasculitis ( AAV ) , but renal outcomes are unknown . This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis ( RAVE ) Trial who had renal involvement ( biopsy proven pauci-immune GN , red blood cell casts in the urine , and /or a rise in serum creatinine concentration attributed to vasculitis ) . Remission-induction regimens were RTX at 375 mg/m(2 ) × 4 or CYC at 2 mg/kg/d . CYC was replaced by AZA ( 2 mg/kg/d ) after 3 - 6 months . Both groups received glucocorticoids . Complete remission ( CR ) was defined as Birmingham Vasculitis Activity Score/Wegener 's Granulomatosis (BVAS/WG)=0 off prednisone . Fifty-two percent ( 102 of 197 ) of the patients had renal involvement at entry . Of these patients , 51 were r and omized to RTX , and 51 to CYC/AZA  . Mean eGFR was lower in the RTX group ( 41 versus 50 ml/min per 1.73 m(2 ) ; P=0.05 ) ; 61 % and 75 % of patients treated with RTX and 63 % and 76 % of patients treated with CYC/AZA achieved CR by 6 and 18 months , respectively . No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type , AAV diagnosis ( granulomatosis with polyangiitis versus microscopic polyangiitis ) , or new diagnosis ( versus relapsing disease ) at entry . There were no differences between treatment groups in relapses at 6 , 12 , or 18 months . No differences in adverse events were observed . In conclusion , patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids BACKGROUND The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe ( organ-threatening ) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown . METHODS In a multicenter , r and omized , double-blind , double-dummy , noninferiority trial , we compared rituximab ( 375 mg per square meter of body-surface area administered once a week for 4 weeks ) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months . The primary outcome measure was complete remission of disease by 6 months , with the remission maintained through 18 months . RESULTS A total of 197 patients were enrolled . As reported previously , 64 % of the patients in the rituximab group , as compared with 53 % of the patients in the cyclophosphamide-azathioprine group , had a complete remission by 6 months . At 12 and 18 months , 48 % and 39 % , respectively , of the patients in the rituximab group had maintained the complete remissions , as compared with 39 % and 33 % , respectively , in the comparison group . Rituximab met the prespecified criteria for noninferiority ( P<0.001 , with a noninferiority margin of 20 % ) . There was no significant difference between the groups in any efficacy measure , including the duration of complete remission and the frequency or severity of relapses . Among the 101 patients who had relapsing disease at baseline , rituximab was superior to conventional immunosuppression at 6 months ( P=0.01 ) and at 12 months ( P=0.009 ) but not at 18 months ( P=0.06 ) , at which time most patients in the rituximab group had reconstituted B cells . There was no significant between-group difference in adverse events . CONCLUSIONS In patients with severe ANCA-associated vasculitis , a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; RAVE Clinical Trials.gov number , NCT00104299 . The aim of the multicentric r and omized trial CYCLOPS is to optimize the treatment of induction of remission in patients with generalized , but not immediately life-threatening ANCA ( antineutrophil cytoplasmic antibodies ) -associated vasculitis . This will be achieved by reducing the dose of cyclophosphamide by administering it as intermittent pulses . The lower cumulative dose will be very probably accompanied with lower toxicity , whereas the effectivity should be comparable . We have enrolled 28 patients to the study . At present , 18 of them are suitable for evaluation . Our preliminary results show that pulse intermittent administration of cyclophosphamide is safer from the point of morbidity and mortality due to infectious complications . In our h and s , this treatment modality does not seem to be less effective than the conventional daily oral cyclophosphamide . However , unambiguous results and treatment recommendations will not be available until the final evaluation of all patients enrolled in the trial BACKGROUND AND OBJECTIVES Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis . This study comprised patients undergoing long-term follow-up who were r and omly allocated to azathioprine after 3 - 6 months or after 12 months of cyclophosphamide treatment . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible . At the time of diagnosis , participants were r and omly allocated to convert to azathioprine after 3 - 6 months ( the azathioprine group ) or after 12 months of cyclophosphamide ( the cyclophosphamide group ) . Patients who did not achieve a remission within 6 months were excluded . This study assessed relapses , ESRD , and death during long-term follow-up . RESULTS Patients were allocated to the azathioprine group ( n=71 ) and the cyclophosphamide group ( n=73 ) . Of these patients , 63 ( 43.8 % ) developed a relapse , 35 ( 24.3 % ) developed a renal relapse , 13 ( 9.0 % ) developed ESRD , and 21 ( 14.6 % ) died . Although there were worse outcomes in the azathioprine group , none were statistically significant . The subdistribution hazard ratio [ sHR ] for relapse was 1.63 ( 95 % confidence interval [ 95 % CI ] , 0.99 to 2.71 ) , the composite of relapse or death hazard ratio [ HR ] was 1.59 ( 95 % CI , 1.00 to 2.54 ) , the ESRD sHR was 1.71 ( 95 % CI , 0.56 to 5.19 ) , and the death HR was 0.75 ( 95 % CI , 0.32 to 1.79 ) . CONCLUSIONS It remains uncertain whether converting to azathioprine after 3 - 6 months of induction cyclophosphamide therapy is as effective as converting after 12 months . Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy BACKGROUND Cytoplasmic anti-neutrophil cytoplasmic antibody ( C-ANCA ) positivity at remission has been associated with an increased relapse rate in patients with proteinase 3 anti-neutrophil cytoplasmic antibody-associated vasculitis ( PR3-AAV ) after a switch to azathioprine maintenance therapy . We therefore hypothesized that extended azathioprine maintenance therapy could reduce the incidence of relapse in this setting . METHODS Patients newly diagnosed with PR3-AAV at 12 centres in The Netherl and s during 2003 - 11 who received a st and ardized induction regimen consisting of oral cyclophosphamide and corticosteroids were enrolled ( n = 131 ) . Patients were r and omized to st and ard or extended azathioprine maintenance therapy  when C-ANCA was positive at the time of stable remission . St and ard maintenance treatment consisted of azathioprine ( 1.5 - 2.0 mg/kg ) until 1 year after diagnosis and subsequent tapering to 25 mg every 3 months . Extended azathioprine maintenance therapy ( 1.5 - 2.0 mg/kg ) was continued until 4 years after diagnosis and tapered thereafter . The primary endpoint was relapse-free survival at 4 years after diagnosis . RESULTS In patients with PR3-AAV who were C-ANCA positive at the time of stable remission , relapse-free survival at 4 years after diagnosis did not differ significantly between st and ard azathioprine ( n = 24 ) and extended azathioprine ( n = 21 ) maintenance therapy ( P = 0.40 ) . There was also no significant difference in relapse-free survival between patients receiving st and ard azathioprine ( n = 106 ) versus extended azathioprine maintenance therapy ( n = 21 ; P = 0.94 ) . In addition , there was no difference in the relapse rate between patients with PR3-AAV who were C-ANCA positive ( n = 45 ) at the time of remission versus patients who became C-ANCA negative at the time of remission ( n = 82 ; P = 0.62 ) . CONCLUSIONS This r and omized trial suggests that extended azathioprine maintenance therapy has only a limited effect on the prevention of relapse in patients with PR3-AAV at 4 years after diagnosis . Moreover , positive C-ANCA status at stable remission was not associated with an increased rate of relapse . TRIAL REGISTRATION Clinical Trials.gov NCT 00128895 Background Bacterial and viral respiratory tract infections may trigger relapses in patients with PR3-positive vasculitis . Data have suggested that treatment with co-trimoxazole may be beneficial , because this antibiotic could act by eliminating the offending microbe and thereby stopping the initiating stimulus . Goal and methods Prospect i ve , r and omized , placebocontrolled study of the efficacy of co-trimoxazole given 960 mg thrice weekly for 18 months in preventing relapses in patients with Wegener 's granulomatosis ( WG ) in remission , after treatment with cyclophosphamide and prednisolone was conducted . Relapses and infections were assessed with predefined criteria based on clinical , laboratory , serological , microbiological , and histopathological findings . Sixteen patients were assigned to receive co-trimoxazole and 15 to receive placebo .  Results Seventy five percent of the patients in the co-trimoxazole group remained in remission at 18 months and 55 % of those in the placebo group . A proportional hazard regression analysis identified a positive PR3-ANCA test at the start of treatment , chronic nasal crusting , and Staphylococus aureus infection as risk factors for relapse . Furthermore , the analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged diseasefree interval . Conclusion Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener 's granulomatosis in remission OBJECTIVE St and ard therapy for antineutrophil cytoplasmic antibody-associated systemic vasculitis ( AASV ) with cyclophosphamide ( CYC ) and prednisolone is limited by toxicity . This unblinded , prospect i ve , r and omized , controlled trial was undertaken to determine whether methotrexate ( MTX ) could replace CYC in the early treatment of AASV . METHODS Patients with newly diagnosed AASV , with serum creatinine levels < 150 mumoles/liter , and without critical organ manifestations of disease were r and omized to receive either st and ard oral CYC , 2 mg/kg/day or oral MTX , 20 - 25 mg/week  ; both groups received the same prednisolone regimen . All drug treatments were gradually tapered and withdrawn by 12 months . Followup continued to 18 months . The primary end point was the remission rate at 6 months ( noninferiority testing ) . RESULTS One hundred patients were recruited from 26 European centers ; 51 patients were r and omized to the MTX group and 49 to the CYC group . At 6 months , the remission rate in patients treated with MTX ( 89.8 % ) was not inferior to that in patients treated with CYC ( 93.5 % ) ( P = 0.041 ) . In the MTX group , remission was delayed among patients with more extensive disease ( P = 0.04 ) or pulmonary involvement ( P = 0.03 ) . Relapse rates at 18 months were 69.5 % in the MTX group and 46.5 % in the CYC group ; the median time from remission to relapse was 13 months and 1 
    Output:
    
Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leucopenia .
Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but result ed in a higher relapse rate when tested against azathioprine in remission maintenance .
Rituximab is an effective remission induction agent .
Oral co-trimoxazole did not reduce relapses significantly in granulomatosis with polyangiitis .
Plasma exchange was effective in patients with severe AKI secondary to vasculitis .
Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose .
Whilst cyclophosphamide is st and ard induction treatment , rituximab and mycophenolate mofetil were also effective .
Azathioprine , methotrexate and leflunomide  were effective as maintenance therapy .