Please use this identifier to cite or link to this item:
https://repository.monashhealth.org/monashhealthjspui/handle/1/37602
Title: | Immunosuppressive treatment for proliferative lupus nephritis. | Authors: | Strippoli G.F.M.;Masson P.;Craig J.C.;Tong A.;Singh-Grewal D.;Flanc R.S.;Roberts M.A.;Webster A.C.;Tunnicliffe D.J.;Palmer S.C.;Henderson L. | Institution: | (Tunnicliffe, Craig, Tong, Webster, Strippoli) The University of Sydney, Sydney School of Public Health, Sydney, NSW 2006, Australia (Tunnicliffe, Tong) The Children's Hospital at Westmead, Centre for Kidney Research, Westmead, Australia (Palmer) University of Otago Christchurch, Department of Medicine, 2 Riccarton Ave, PO Box 4345, Christchurch 8140, New Zealand (Henderson) NHS Lothian, Renal Department, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom (Masson) Royal Free London NHS Foundation Trust, Department of Renal Medicine, London, United Kingdom (Craig, Webster, Strippoli) The Children's Hospital at Westmead, Cochrane Kidney and Transplant, Centre for Kidney Research, Westmead, NSW 2145, Australia (Craig) Flinders University, College of Medicine and Public Health, Adelaide, SA 5001, Australia (Singh-Grewal) The Sydney Children's Hospitals Network, Department Paediatric Rheumatology, The Children's Hospital at Westmead, Cnr Hainsworth and Hawkesbury Roads, Westmead, NSW 2145, Australia (Flanc) Monash Medical Centre, Department of Nephrology, Clayton Rd, Clayton, VIC 3168, Australia (Roberts) Monash University, Eastern Health Clinical School, Box Hill, VIC 3128, Australia (Webster) The University of Sydney at Westmead, Centre for Transplant and Renal Research, Westmead Millennium Institute, Westmead, NSW 2145, Australia (Strippoli) University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy (Strippoli) Diaverum, Medical Scientific Office, Lund, Sweden (Strippoli) Diaverum Academy, Bari, Italy | Issue Date: | 6-Jul-2018 | Copyright year: | 2018 | Publisher: | John Wiley and Sons Ltd (Southern Gate, Chichester, West Sussex PO19 8SQ, United Kingdom. E-mail: vgorayska@wiley.com) | Place of publication: | United Kingdom | Publication information: | Cochrane Database of Systematic Reviews. 2018 (6) (no pagination), 2018. Article Number: CD002922. Date of Publication: 29 Jun 2018. | Journal: | Cochrane Database of Systematic Reviews | Abstract: | Background: Cyclophosphamide, in combination with corticosteroids, has been first-line treatment for inducing disease remission for proliferative lupus nephritis, reducing death at five years from over 50% in the 1950s and 1960s to less than 10% in recent years. Several treatment strategies designed to improve remission rates and minimise toxicity have become available. Treatments, including mycophenolate mofetil (MMF) and calcineurin inhibitors, alone and in combination, may have equivalent or improved rates of remission, lower toxicity (less alopecia and ovarian failure) and uncertain effects on death, end-stage kidney disease (ESKD) and infection. This is an update of a Cochrane review first published in 2004 and updated in 2012. Objective(s): Our objective was to assess the evidence and evaluate the benefits and harms of different immunosuppressive treatments in people with biopsy-proven lupus nephritis. The following questions relating to management of proliferative lupus nephritis were addressed: 1) Are new immunosuppressive agents superior to or as effective as cyclophosphamide plus corticosteroids? 2) Which agents, dosages, routes of administration and duration of therapy should be used? 3) Which toxicities occur with the different treatment regimens? Search methods: We searched the Cochrane Kidney and Transplant Specialised Register up to 2 March 2018 with support from the Cochrane Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive treatment for biopsy-proven class III, IV, V+III and V+VI lupus nephritis in adult or paediatric patients were included. Data Collection and Analysis: Data were abstracted and the risks of bias were assessed independently by two authors. Dichotomous outcomes were calculated as risk ratio (RR) and measures on continuous scales calculated as mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were death (all causes) and complete disease remission for induction therapy and disease relapse for maintenance therapy. Evidence certainty was determined using GRADE. Main Result(s): In this review update, 26 new studies were identified, to include 74 studies involving 5175 participants overall. Twenty-nine studies included children under the age of 18 years with lupus nephritis, however only two studies exclusively examined the treatment of lupus nephritis in patients less than 18 years of age. Induction therapy Sixty-seven studies (4791 participants; median 12 months duration (range 2.5 to 48 months)) reported induction therapy. The effects of all treatment strategies on death (all causes) and ESKD were uncertain (very low certainty evidence) as this outcome occurred very infrequently. Compared with intravenous (IV) cyclophosphamide, MMF may have increased complete disease remission (RR 1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects includes the possibility of little or no difference. Compared to IV cyclophosphamide, MMF is probably associated with decreased alopecia (RR 0.29, 95% CI 0.19 to 0.46; 170 less (129 less to 194 less) per 1000 people) (moderate certainty evidence), increased diarrhoea (RR 2.42, 95% CI 1.64 to 3.58; 142 more (64 more to 257 more) per 1000 people) (moderate certainty evidence) and may have made little or no difference to major infection (RR 1.02, 95% CI 0.67 to 1.54; 2 less (38 less to 62 more) per 1000 people) (low certainty evidence). It is uncertain if MMF decreased ovarian failure compared to IV cyclophosphamide because the certainty of the evidence was very low (RR 0.36, 95% CI 0.06 to 2.18; 26 less (39 less to 49 more) per 1000 people). Studies were not generally designed to measure ESKD. MMF combined with tacrolimus may have increased complete disease remission (RR 2.38, 95% CI 1.07 to 5.30; 336 more (17 to 1048 more) per 1000 people (low certainty evidence) compared with IV cyclophosphamide, however the effects on alopecia, diarrhoea, ovarian failure, and major infection remain uncertain. Compared to standard of care, the effects of biologics on most outcomes were uncertain because of low to very low certainty of evidence. Maintenance therapy Nine studies (767 participants; median 30 months duration (range 6 to 63 months)) reported maintenance therapy. In maintenance therapy, disease relapse is probably increased with azathioprine compared with MMF (RR 1.75, 95% CI 1.20 to 2.55; 114 more (30 to 236 more) per 1000 people (moderate certainty evidence). Multiple other interventions were compared as maintenance therapy, but patient-outcome data were sparse leading to imprecise estimates. Authors' conclusions: In this review update, studies assessing treatment for proliferative lupus nephritis were not designed to assess death (all causes) or ESKD. MMF may lead to increased complete disease remission compared with IV cyclophosphamide, with an acceptable adverse event profile, although evidence certainty was low and included the possibility of no difference. Calcineurin combined with lower dose MMF may improve induction of disease remission compared with IV cyclophosphamide, but the comparative safety profile of these therapies is uncertain. Azathioprine may increase disease relapse as maintenance therapy compared with MMF.Copyright © 2018 The Cochrane Collaboration. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1002/14651858.CD002922.pub4 | Link to associated publication: | Click here for full text options | PubMed URL: | 29957821 [http://www.ncbi.nlm.nih.gov/pubmed/?term=29957821] | ISSN: | 1469-493X (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/37602 | Type: | Review | Subjects: | leukopenia/si [Side Effect] low drug dose *lupus erythematosus nephritis/dt [Drug Therapy] *lupus erythematosus nephritis/th [Therapy] lupus erythematosus nephritis/dt [Drug Therapy] maintenance therapy malignant neoplasm/si [Side Effect] menstrual irregularity/si [Side Effect] morning dosage multiple cycle treatment nausea/si [Side Effect] ovary insufficiency/si [Side Effect] plasma exchange priority journal proteinuria randomized controlled trial (topic) relapse remission review SLEDAI systematic review vomiting/si [Side Effect] abatacept/ae [Adverse Drug Reaction] abatacept/ct [Clinical Trial] abatacept/cb [Drug Combination] abatacept/cm [Drug Comparison] abatacept/dt [Drug Therapy] atacicept/ct [Clinical Trial] atacicept/cb [Drug Combination] atacicept/cm [Drug Comparison] atacicept/dt [Drug Therapy] azathioprine/ae [Adverse Drug Reaction] azathioprine/ct [Clinical Trial] azathioprine/cb [Drug Combination] azathioprine/cm [Drug Comparison] azathioprine/dt [Drug Therapy] azathioprine/po [Oral Drug Administration] calcineurin inhibitor/ae [Adverse Drug Reaction] calcineurin inhibitor/ct [Clinical Trial] calcineurin inhibitor/cb [Drug Combination] calcineurin inhibitor/cm [Drug Comparison] calcineurin inhibitor/dt [Drug Therapy] corticosteroid/ae [Adverse Drug Reaction] corticosteroid/ct [Clinical Trial] corticosteroid/ad [Drug Administration] corticosteroid/cb [Drug Combination] corticosteroid/dt [Drug Therapy] corticosteroid/iv [Intravenous Drug Administration] corticosteroid/po [Oral Drug Administration] cyclophosphamide/ae [Adverse Drug Reaction] cyclophosphamide/ct [Clinical Trial] cyclophosphamide/ad [Drug Administration] cyclophosphamide/cb [Drug Combination] cyclophosphamide/cm [Drug Comparison] cyclophosphamide/dt [Drug Therapy] cyclophosphamide/iv [Intravenous Drug Administration] cyclophosphamide/po [Oral Drug Administration] cyclosporine/ct [Clinical Trial] cyclosporine/cb [Drug Combination] cyclosporine/cm [Drug Comparison] cyclosporine/dt [Drug Therapy] cyclosporine/po [Oral Drug Administration] glucocorticoid/cb [Drug Combination] glucocorticoid/dt [Drug Therapy] glucocorticoid/po [Oral Drug Administration] immunoglobulin/ct [Clinical Trial] immunoglobulin/cm [Drug Comparison] immunoglobulin/dt [Drug Therapy] immunoglobulin/iv [Intravenous Drug Administration] immunosuppressive agent/ct [Clinical Trial] immunosuppressive agent/cb [Drug Combination] immunosuppressive agent/cm [Drug Comparison] immunosuppressive agent/dt [Drug Therapy] immunosuppressive agent/sc [Subcutaneous Drug Administration] laquinimod/ct [Clinical Trial] laquinimod/cb [Drug Combination] laquinimod/cm [Drug Comparison] laquinimod/dt [Drug Therapy] laquinimod/po [Oral Drug Administration] leflunomide/ct [Clinical Trial] leflunomide/cb [Drug Combination] leflunomide/cm [Drug Comparison] leflunomide/dt [Drug Therapy] leflunomide/po [Oral Drug Administration] methylprednisolone/ct [Clinical Trial] methylprednisolone/cb [Drug Combination] methylprednisolone/cm [Drug Comparison] methylprednisolone/dt [Drug Therapy] methylprednisolone/iv [Intravenous Drug Administration] misoprostol/ct [Clinical Trial] misoprostol/cb [Drug Combination] misoprostol/cm [Drug Comparison] misoprostol/dt [Drug Therapy] misoprostol/po [Oral Drug Administration] mycophenolate mofetil/ae [Adverse Drug Reaction] mycophenolate mofetil/ct [Clinical Trial] mycophenolate mofetil/cb [Drug Combination] mycophenolate mofetil/cm [Drug Comparison] mycophenolate mofetil/dt [Drug Therapy] mycophenolate mofetil/po [Oral Drug Administration] mycophenolic acid/ct [Clinical Trial] mycophenolic acid/cb [Drug Combination] mycophenolic acid/dt [Drug Therapy] ocrelizumab/ae [Adverse Drug Reaction] ocrelizumab/ct [Clinical Trial] ocrelizumab/cb [Drug Combination] ocrelizumab/cm [Drug Comparison] ocrelizumab/dt [Drug Therapy] placebo prednisolone/ct [Clinical Trial] prednisolone/cb [Drug Combination] prednisolone/cm [Drug Comparison] prednisolone/dt [Drug Therapy] prednisolone/po [Oral Drug Administration] prednisone/ae [Adverse Drug Reaction] prednisone/ct [Clinical Trial] prednisone/cb [Drug Combination] prednisone/cm [Drug Comparison] prednisone/dt [Drug Therapy] prednisone/po [Oral Drug Administration] rituximab/ae [Adverse Drug Reaction] rituximab/ct [Clinical Trial] rituximab/cb [Drug Combination] rituximab/cm [Drug Comparison] rituximab/dt [Drug Therapy] sirukumab/ae [Adverse Drug Reaction] sirukumab/ct [Clinical Trial] sirukumab/cb [Drug Combination] sirukumab/cm [Drug Comparison] sirukumab/dt [Drug Therapy] sirukumab/iv [Intravenous Drug Administration] tacrolimus/ae [Adverse Drug Reaction] tacrolimus/ct [Clinical Trial] tacrolimus/cb [Drug Combination] tacrolimus/cm [Drug Comparison] tacrolimus/dt [Drug Therapy] tacrolimus/po [Oral Drug Administration] unclassified drug voclosporin/ct [Clinical Trial] voclosporin/cb [Drug Combination] voclosporin/cm [Drug Comparison] voclosporin/dt [Drug Therapy] AMG 811/ct [Clinical Trial] AMG 811/cm [Drug Comparison] AMG 811/sc [Subcutaneous Drug Administration] AMG 811/dt [Drug Therapy] all cause mortality alopecia/si [Side Effect] biological therapy bladder disease/si [Side Effect] bone disease/si [Side Effect] creatinine blood level creatinine clearance diarrhea/si [Side Effect] disease activity dosage schedule comparison drug dose comparison drug dose increase drug dose reduction drug dose titration drug megadose drug withdrawal end stage renal disease gastrointestinal symptom/si [Side Effect] herpes zoster/si [Side Effect] human immunoadsorption *immunosuppressive treatment infection/si [Side Effect] drug dose titration drug megadose drug withdrawal end stage renal disease gastrointestinal symptom / side effect herpes zoster / side effect human immunoadsorption *immunosuppressive treatment infection / side effect leukopenia / side effect low drug dose *lupus erythematosus nephritis / *drug therapy / *therapy lupus erythematosus nephritis / drug therapy maintenance therapy malignant neoplasm / side effect menstrual irregularity / side effect morning dosage multiple cycle treatment nausea / side effect ovary insufficiency / side effect plasma exchange priority journal proteinuria randomized controlled trial (topic) relapse bone disease / side effect Review SLEDAI systematic review vomiting / side effect bladder disease / side effect biological therapy alopecia / side effect all cause mortality remission creatinine blood level creatinine clearance diarrhea / side effect disease activity dosage schedule comparison drug dose comparison drug dose increase drug dose reduction |
Type of Clinical Study or Trial: | Systematic review and/or meta-analysis |
Appears in Collections: | Articles |
Show full item record
Items in Monash Health Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.