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Health Technology Assessment... Aug 2016End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival.
OBJECTIVES
To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation.
DATA SOURCES
Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost).
REVIEW METHODS
Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.
RESULTS
Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC.
LIMITATIONS
The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.
CONCLUSIONS
TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014013544.
FUNDING
The National Institute for Health Research HTA programme.
Topics: Abatacept; Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Basiliximab; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Everolimus; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Models, Economic; Mycophenolic Acid; Recombinant Fusion Proteins; Sirolimus; Tacrolimus; Technology Assessment, Biomedical
PubMed: 27557331
DOI: 10.3310/hta20610 -
Archives of Dermatological Research Jun 2024Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains... (Review)
Review
Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains uncertain due to limited systematic evidence. Our objective was to analyze antistreptococcal therapies' effectiveness in improving psoriasis. We conducted a systematic review following PRISMA guidelines, evaluating antistreptococcal treatment efficacy in psoriasis patients from PubMed, Scopus, and Embase databases until August 14, 2022. Eligible studies included psoriasis patients undergoing antistreptococcal therapy, regardless of demographics or psoriasis type. 50 studies (1778 patients) were analyzed, with penicillins/aminopenicillins as the most studied antibiotics (21 studies), showing mixed outcomes, some reporting significant improvement in guttate psoriasis, while others showed no significant difference. Rifampin demonstrated positive results in most of ten studies, and macrolides showed varying effectiveness in two studies. Tonsillectomy in 14 studies (409 patients) mainly focusing on guttate and chronic plaque psoriasis showed positive outcomes, indicating improved symptoms and quality of life. Limitations include heterogeneous studies, sampling bias, and quality of evidence. This systematic review reveals limited and varied evidence for systemic antibiotic therapy efficacy in psoriasis treatment, while tonsillectomy emerges as a potentially beneficial antistreptococcal option, urging further well-designed, controlled studies with larger sample sizes and standardized protocols for better comparisons.
Topics: Humans; Psoriasis; Anti-Bacterial Agents; Streptococcal Infections; Treatment Outcome; Quality of Life; Penicillins; Rifampin
PubMed: 38850287
DOI: 10.1007/s00403-024-03051-8 -
Pediatrics Jul 2015Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and... (Review)
Review
BACKGROUND
Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region.
METHODS
We determined the relationship between rates of isoniazid resistance among child cases and among treatment-naive adult cases through a systematic literature review. We applied this relationship to regional isoniazid resistance estimates to estimate proportions of childhood tuberculosis cases with isoniazid resistance. We applied these proportions to childhood tuberculosis incidence estimates to estimate numbers of children with isoniazid-resistant tuberculosis.
RESULTS
We estimated 12.1% (95% confidence interval [CI] 9.8% to 14.8%) of all children with tuberculosis had isoniazid-resistant disease, representing 120,872 (95% CI 96,628 to 149,059) incident cases of isoniazid-resistant tuberculosis in children in 2010. The majority of these occurred in the Western Pacific and Southeast Asia regions; the European region had the highest proportion of child tuberculosis cases with isoniazid resistance, 26.1% (95% CI: 20.0% to 33.6%).
CONCLUSIONS
The burden of isoniazid-resistant tuberculosis in children is substantial, and risk varies considerably by setting. The large number of child cases signals extensive ongoing transmission from adults with isoniazid-resistant tuberculosis. The risk of isoniazid resistance must be considered when evaluating treatment options for children with disease or latent infection to avoid inadequate treatment and consequent poor outcomes.
Topics: Antitubercular Agents; Global Health; Humans; Incidence; Isoniazid; Tuberculosis, Multidrug-Resistant
PubMed: 26034243
DOI: 10.1542/peds.2015-0172 -
The International Journal of... Apr 2016D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA-agonist has... (Review)
Review
D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA-agonist has been found. In this review, we evaluate its therapeutic potential in neuropsychological disorders and discuss its pitfalls in terms of dosing and application frequency as well as its safety in low-dose therapy. Therefore, we identified 91 clinical trials by performing a Medline search. We demonstrate in part preliminary but increasing evidence that D-cycloserine may be effective in various psychiatric diseases, including schizophrenia, anxiety disorders, addiction, eating disorders, major depression, and autism as well as in neurological diseases, including dementia, Alzheimer's disease, and spinocerebellar degeneration. D-Cycloserine in low-dose therapy is safe, but there is still a need for new drugs with higher specificity to the different N-methyl-D-aspartate-receptor subunits.
Topics: Animals; Cycloserine; Excitatory Amino Acid Agonists; Humans; Mental Disorders; Nervous System Diseases; Psychotropic Drugs; Receptors, N-Methyl-D-Aspartate
PubMed: 26364274
DOI: 10.1093/ijnp/pyv102 -
BMC Medicine Feb 2018Multidrug-resistant tuberculosis (MDR-TB) is a growing concern in meeting global targets for TB control. In high-income low-TB-incidence countries, a disproportionate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multidrug-resistant tuberculosis (MDR-TB) is a growing concern in meeting global targets for TB control. In high-income low-TB-incidence countries, a disproportionate number of MDR-TB cases occur in migrant (foreign-born) populations, with concerns about low adherence rates in these patients compared to the host non-migrant population. Tackling MDR-TB in this context may, therefore, require unique approaches. We conducted a systematic review and meta-analysis to identify and synthesise data on MDR-TB treatment adherence in migrant patients to inform evidence-based strategies to improve care pathways and health outcomes in this group.
METHODS
This systematic review and meta-analysis was conducted in line with PRISMA guidelines (PROSPERO 42017070756). The databases Embase, MEDLINE, Global Health and PubMed were searched to 24 May 2017 for primary research reporting MDR-TB treatment adherence and outcomes in migrant populations, with no restrictions on dates or language. A meta-analysis was conducted using random-effects models.
RESULTS
From 413 papers identified in the database search, 15 studies reporting on MDR-TB treatment outcomes for 258 migrants and 174 non-migrants were included in the systematic review and meta-analysis. The estimated rate of adherence to MDR-TB treatment across migrant patients was 71% [95% confidence interval (CI) = 58-84%], with non-adherence reported among 20% (95% CI = 4-37%) of migrant patients. A key finding was that there were no differences in estimated rates of adherence [risk ratio (RR) = 1.05; 95% CI = 0.82-1.34] or non-adherence (RR = 0.97; 95% CI = 0.79-1.36) between migrants and non-migrants.
CONCLUSIONS
MDR-TB treatment adherence rates among migrants in high-income low-TB-incidence countries are approaching global targets for treatment success (75%), and are comparable to rates in non-migrants. The findings highlight that only just over 70% of migrant and non-migrant patients adhere to MDR-TB treatment. The results point to the importance of increasing adherence in all patient groups, including migrants, with an emphasis on tailoring care based on social risk factors for poor adherence. We believe that MDR-TB treatment targets are not ambitious enough.
Topics: Antitubercular Agents; Humans; Transients and Migrants; Treatment Adherence and Compliance; Tuberculosis, Multidrug-Resistant
PubMed: 29466983
DOI: 10.1186/s12916-017-1001-7 -
The International Journal of... Nov 2017To reduce transmission and improve patient outcomes, rapid diagnosis and treatment of rifampicin-resistant tuberculosis (RR-TB) is required. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To reduce transmission and improve patient outcomes, rapid diagnosis and treatment of rifampicin-resistant tuberculosis (RR-TB) is required.
OBJECTIVE
To conduct a systematic review and meta-analysis assessing time to treatment for RR-TB and variability using diagnostic testing methods and treatment delivery approach.
DESIGN
Studies from 2000 to 2015 reporting time to second-line treatment initiation were selected from PubMed and published conference abstracts.
RESULTS
From 53 studies, 83 cohorts (13 034 patients) were included. Overall weighted mean time to treatment from specimen collection was 81 days (95%CI 70-91), and was shorter with ambulatory (57 days, 95%CI 40-74) than hospital-based treatment (86 days, 95%CI 71-102). Time to treatment was shorter with genotypic susceptibility testing (38 days, 95%CI 27-49) than phenotypic testing (108 days, 95%CI 98-117). The mean percentage of diagnosed patients initiating treatment was 76% (95%CI 70-83, range 25-100).
CONCLUSION
Time to second-line anti-tuberculosis treatment initiation is extremely variable across studies, and often unnecessarily long. Reduced delays are associated with genotypic testing and ambulatory treatment settings. Routine monitoring of the proportion of diagnosed patients initiating treatment and time to treatment are necessary to identify areas for intervention.
Topics: Ambulatory Care; Antitubercular Agents; Genotype; Hospitalization; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Time-to-Treatment; Tuberculosis, Multidrug-Resistant
PubMed: 29037299
DOI: 10.5588/ijtld.17.0230 -
Frontiers in Immunology 2023IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue. The aim of this study was to conduct a systematic review and meta-analysis to assess risk factors and outcomes for IgA nephropathy recurrence.
METHODS
We used PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM to search for relevant studies published in English and Chinese. Cohort or case-control studies reporting risk factors or outcomes for IgA nephropathy recurrence were included.
RESULTS
Fifty-eight studies were included. Compare to no recurrence group, those with IgAN recurrence had younger age (mean difference [MD]=-4.27 years; risk ratio [RR]=0.96), younger donor age (MD=-2.19 years), shorter time from IgA nephropathy diagnosis to end stage renal disease (MD=-1.84 years; RR=0.94), shorter time on dialysis (MD=-3.14 months), lower human leukocyte-antigen (HLA) mismatches (MD=-0.11) and HLA-DR mismatches (MD=-0.13). HLA-B46 antigen (RR=0.39), anti-IL-2-R antibodies induction (RR=0.68), mycophenolate mofetil (RR=0.69), and pretransplant tonsillectomy (RR=0.43) were associated with less IgAN recurrence. Of note, male recipient gender (RR=1.17), related donor (RR=1.53), retransplantation (RR=1.43), hemodialysis (RR=1.68), no induction therapy (RR=1.73), mTOR inhibitor (RR=1.51), angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (RR=1.63) were risk factors for IgAN recurrence. Recurrence increased the risk of graft loss (RR=2.19).
CONCLUSIONS
This study summarized the risk factors for recurrence of IgA nephropathy after kidney transplantation. Well-designed prospective studies are warranted for validation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=377480, identifier CRD42022377480.
Topics: Humans; Male; Glomerulonephritis, IGA; Kidney Transplantation; Risk Factors; Kidney Failure, Chronic; Mycophenolic Acid
PubMed: 38090563
DOI: 10.3389/fimmu.2023.1277017 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914 -
BMC Gastroenterology Feb 2023Gastrointestinal strictures impact clinical presentation in abdominal tuberculosis and are associated with significant morbidity. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastrointestinal strictures impact clinical presentation in abdominal tuberculosis and are associated with significant morbidity.
AIM
To conduct a systematic review of the prevalence of stricturing disease in abdominal and gastrointestinal tuberculosis and response to antitubercular therapy (ATT).
METHODS
We searched Pubmed and Embase on 13th January 2022, for papers reporting on the frequency and outcomes of stricturing gastrointestinal tuberculosis. The data were extracted, and pooled prevalence of stricturing disease was estimated in abdominal tuberculosis and gastrointestinal (intestinal) tuberculosis. The pooled clinical response and stricture resolution (endoscopic or radiologic) rates were also estimated. Publication bias was assessed using the Funnel plot and Egger test. The risk of bias assessment was done using a modified Newcastle Ottawa Scale.
RESULTS
Thirty-three studies reporting about 1969 patients were included. The pooled prevalence of intestinal strictures in abdominal tuberculosis and gastrointestinal TB was 0.12 (95%CI 0.07-0.20, I = 89%) and 0.27 (95% CI 0.21-0.33, I = 85%), respectively. The pooled clinical response of stricturing gastrointestinal tuberculosis to antitubercular therapy was 0.77 (95%CI 0.65-0.86, I = 74%). The pooled stricture response rate (endoscopic or radiological) was 0.66 (95%CI 0.40-0.85, I = 91%). The pooled rate of need for surgical intervention was 0.21 (95%CI 0.13-0.32, I = 70%), while endoscopic dilatation was 0.14 (95%CI 0.09-0.21, I = 0%).
CONCLUSION
Stricturing gastrointestinal tuberculosis occurs in around a quarter of patients with gastrointestinal tuberculosis, and around two-thirds of patients have a clinical response with antitubercular therapy. A subset of patients may need endoscopic or surgical intervention. The estimates for the pooled prevalence of stricturing disease and response to ATT had significant heterogeneity.
Topics: Humans; Constriction, Pathologic; Tuberculosis, Gastrointestinal; Antitubercular Agents; Intestinal Obstruction; Abdomen
PubMed: 36814249
DOI: 10.1186/s12876-023-02682-x -
The Cochrane Database of Systematic... Jun 2018Cyclophosphamide, in combination with corticosteroids, has been first-line treatment for inducing disease remission for proliferative lupus nephritis, reducing death at... (Meta-Analysis)
Meta-Analysis Review
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.
OBJECTIVES
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 RESULTS
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 therapyNine 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.
Topics: Adult; Azathioprine; Calcineurin; Child; Cyclophosphamide; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Induction Chemotherapy; Lupus Nephritis; Maintenance Chemotherapy; Male; Mycophenolic Acid; Randomized Controlled Trials as Topic; Recurrence; Tacrolimus
PubMed: 29957821
DOI: 10.1002/14651858.CD002922.pub4