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Clinical Nephrology May 2018To seek an optimized immunotherapy which can preserve renal function while maintaining low acute rejection rates, we conducted a systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of everolimus plus low-dose calcineurin inhibitor vs. mycophenolate mofetil plus standard-dose calcineurin inhibitor in renal transplant recipients: A systematic review and meta-analysis .
BACKGROUND
To seek an optimized immunotherapy which can preserve renal function while maintaining low acute rejection rates, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of everolimus (EVR) plus low-dose calcineurin inhibitor (CNI) vs. mycophenolate mofetil (MMF) plus standard-dose CNI regimen after kidney transplantation (KT).
MATERIALS AND METHODS
We searched for RCTs comparing the outcomes of EVR plus low-dose CNI and MMF plus standard-dose CNI regimen after KT and identified eligible RCTs according to strict inclusion and exclusion criteria. Two authors independently assessed the quality of included studies and performed a meta-analysis using RevMan5.3.
RESULTS
Eleven RCTs with 850 renal transplant recipients were included. This meta-analysis showed that EVR plus low-dose CNI regimen was associated with comparable renal function (standardized mean difference (SMD) 0.16, 95% CI (-0.03, 0.35), p = 0.09) and a similar rate of acute rejection (risk ratio (RR) 1.16, 95% CI (0.96, 1.42), p = 0.13), graft loss (RR 0.89, 95% CI (0.63, 1.24), p = 0.49) and mortality (RR 1.19, 95% CI (0.69, 2.08), p = 0.53) compared to MMF plus standard-dose CNI regimen. In addition, EVR plus low-dose CNI regimen could reduce the rate of cytomegalovirus and infection, whereas a lower rate of other adverse events were noted in MMF plus standard-dose CNI regimen.
CONCLUSION
EVR plus low-dose CNI regimen was similar in efficacy and safety to MMF plus standard-dose CNI regimen after KT. However, this should be confirmed by further studies. .
Topics: Calcineurin Inhibitors; Everolimus; Humans; Kidney Transplantation; Mycophenolic Acid
PubMed: 29292693
DOI: 10.5414/CN109287 -
BMJ (Clinical Research Ed.) Jun 2015To compare the clinical efficacy and bioequivalence of generic immunosuppressive drugs in patients with solid organ transplants. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the clinical efficacy and bioequivalence of generic immunosuppressive drugs in patients with solid organ transplants.
DESIGN
Systematic review and meta-analysis of all studies comparing generic with innovator immunosuppressive drugs.
DATA SOURCES
Medline and Embase from 1980 to September 2014.
REVIEW METHODS
A literature search was performed for all studies comparing a generic to an innovator immunosuppressive drug in solid organ transplantation. Two reviewers independently extracted data and assessed quality of studies. Meta-analyses of prespecified outcomes were performed when deemed appropriate. Outcomes included patient survival, allograft survival, acute rejection, adverse events and bioequivalence.
RESULTS
1679 citations were screened, of which 50 studies met eligibility criteria (17 randomized trials, 15 non-randomized interventional studies, and 18 observational studies). Generics were compared with Neoral (cyclosporine) (32 studies), Prograf (tacrolimus) (12 studies), and Cellcept (mycophenolate mofetil) (six studies). Pooled analysis of randomized controlled trials in patients with kidney transplants that reported bioequivalence criteria showed that Neoral (two studies) and Prograf (three studies) were not bioequivalent with generic preparations according to criteria of the European Medicines Agency. The single Cellcept trial also did not meet bioequivalence. Acute rejection was rare but did not differ between groups. For Neoral, the pooled Peto odds ratio was 1.23 (95% confidence interval 0.64 to 2.36) for kidney randomized controlled trials and 0.66 (0.40 to 1.08) for observational studies. For kidney observational studies, the pooled Peto odds ratios were 0.98 (0.37 to 2.60) for Prograf and 0.49 (0.09 to 2.56) for Cellcept. Meta-analyses for non-renal solid organ transplants were not performed because of a lack of data.There were insufficient data reported on patient or graft survival. Pooling of results was limited by inconsistent study methods and reporting of outcomes. Many studies did not report standard criteria used to determine bioequivalence. While rates of acute rejection seemed similar and were relatively rare, few studies were designed to properly compare clinical outcomes. Most studies had short follow-up times and included stable patients without a history of rejection.
CONCLUSIONS
High quality data showing bioequivalence and clinical efficacy of generic immunosuppressive drugs in patients with transplants are lacking. Given the serious consequences of rejection and allograft failure, well designed studies on bioequivalence and safety of generic immunosuppression in transplant recipients are needed.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Drugs, Generic; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Organ Transplantation; Prognosis; Survival Analysis; Treatment Outcome
PubMed: 26101226
DOI: 10.1136/bmj.h3163 -
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 -
The Cochrane Database of Systematic... Jul 2022Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.
OBJECTIVES
To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).
SEARCH METHODS
We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February 2022.
SELECTION CRITERIA
We included RCTs that compared HSCT to immunomodulators in the treatment of SSc.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence using standard Cochrane methods.
MAIN RESULTS
We included three RCTs evaluating: non-myeloablative non-selective HSCT (10 participants), non-myeloablative selective HSCT (79 participants), and myeloablative selective HSCT (36 participants). The comparator in all studies was cyclophosphamide (123 participants). The study examining non-myeloablative non-selective HSCT had a high risk of bias given the differences in baseline characteristics between the two arms. The other studies had a high risk of detection bias for participant-reported outcomes. The studies had follow-up periods of one to 4.5 years. Most participants had severe disease, mean age 40 years, and the duration of disease was less than three years. Efficacy No study demonstrated an overall mortality benefit of HSCT when compared to cyclophosphamide. However, non-myeloablative selective HSCT showed overall survival benefits using Kaplan-Meier curves at 10 years and myeloablative selective HSCT at six years. We graded our certainty of evidence as moderate for non-myeloablative selective HSCT and myeloablative selective HSCT. Certainty of evidence was low for non-myeloablative non-selective HSCT. Event-free survival was improved compared to cyclophosphamide with non-myeloablative selective HSCT at 48 months (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.16 to 0.74; moderate-certainty evidence). There was no improvement with myeloablative selective HSCT at 54 months (HR 0.54 95% CI 0.23 to 1.27; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not report event-free survival. There was improvement in functional ability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI, scale from 0 to 3 with 3 being very severe functional impairment) with non-myeloablative selective HSCT after two years with a mean difference (MD) of -0.39 (95% CI -0.72 to -0.06; absolute treatment benefit (ATB) -13%, 95% CI -24% to -2%; relative percent change (RPC) -27%, 95% CI -50% to -4%; low-certainty evidence). Myeloablative selective HSCT demonstrated a risk ratio (RR) for improvement of 3.4 at 54 months (95% CI 1.5 to 7.6; ATB -37%, 95% CI -18% to -57%; RPC -243%, 95% CI -54% to -662%; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; low-certainty evidence). The non-myeloablative non-selective HSCT trial did not report HAQ-DI results. All transplant modalities showed improvement of modified Rodnan skin score (mRSS) (scale from 0 to 51 with the higher number being more severe skin thickness) favoring HSCT over cyclophosphamide. At two years, non-myeloablative selective HSCT showed an MD in mRSS of -11.1 (95% CI -14.9 to -7.3; ATB -22%, 95% CI -29% to -14%; RPC -43%, 95% CI -58% to -28%; moderate-certainty evidence). At 54 months, myeloablative selective HSCT at showed a greater improvement in skin scores than the cyclophosphamide group (RR 1.51, 95% CI 1.06 to 2.13; ATB -27%, 95% CI -6% to -47%; RPC -51%, 95% CI -6% to -113%; moderate-certainty evidence). The NNTB was 4 (95% CI 3 to 18). At one year, for non-myeloablative non-selective HSCT the MD was -16.00 (95% CI -26.5 to -5.5; ATB -31%, 95% CI -52% to -11%; RPC -84%, 95% CI -139% to -29%; low-certainty evidence). No studies reported data on pulmonary arterial hypertension. Adverse events In the non-myeloablative selective HSCT study, there were 51/79 serious adverse events with HSCT and 30/77 with cyclophosphamide (RR 1.7, 95% CI 1.2 to 2.3), with an absolute risk increase of 26% (95% CI 10% to 41%), and a relative percent increase of 66% (95% CI 20% to 129%). The number needed to treat for an additional harmful outcome was 4 (95% CI 3 to 11) (moderate-certainty evidence). In the myeloablative selective HSCT study, there were similar rates of serious adverse events between groups (25/34 with HSCT and 19/37 with cyclophosphamide; RR 1.43, 95% CI 0.99 to 2.08; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not clearly report serious adverse events.
AUTHORS' CONCLUSIONS
Non-myeloablative selective and myeloablative selective HSCT had moderate-certainty evidence for improvement in event-free survival, and skin thicknesscompared to cyclophosphamide. There is also low-certainty evidence that these modalities of HSCT improve physical function. However, non-myeloablative selective HSCT and myeloablative selective HSCT resulted in more serious adverse events than cyclophosphamide; highlighting the need for careful risk-benefit considerations for people considering these HSCTs. Evidence for the efficacy and adverse effects of non-myeloablative non-selective HSCT is limited at this time. Due to evidence provided from one study with high risk of bias, we have low-certainty evidence that non-myeloablative non-selective HSCT improves outcomes in skin scores, forced vital capacity, and safety. Two modalities of HSCT appeared to be a promising treatment option for SSc though there is a high risk of early treatment-related mortality and other adverse events. Additional research is needed to determine the effectiveness and adverse effects of non-myeloablative non-selective HSCT in the treatment of SSc. Also, more studies will be needed to determine how HSCT compares to other treatment options such as mycophenolate mofetil, as cyclophosphamide is no longer the first-line treatment for SSc. Finally, there is a need for a greater understanding of the role of HSCT for people with SSc with significant comorbidities or complications from SSc that were excluded from the trial criteria.
Topics: Adult; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Randomized Controlled Trials as Topic; Scleroderma, Systemic
PubMed: 35904231
DOI: 10.1002/14651858.CD011819.pub2 -
Vaccine Jun 2023Patients with autoimmune rheumatic diseases (ARD) are at a potentially higher risk for COVID-19 infection complications. Given their inherent altered immune system and... (Review)
Review
BACKGROUND
Patients with autoimmune rheumatic diseases (ARD) are at a potentially higher risk for COVID-19 infection complications. Given their inherent altered immune system and the use of immunomodulatory medications, vaccine immunogenicity could be unpredictable with a suboptimal or even an exaggerated immunological response. The aim of this study is to provide real-time data on the emerging evidence of COVID-19 vaccines' efficacy and safety in patients with ARDs.
METHODS
We performed a literature search of the PubMed, EMBASE, and OVID databases up to 11-13 April 2022 on the efficacy and safety of both types of the mRNA-vaccines and the AstraZeneca COVID-19 vaccines in patients with ARD. The risk of bias in the retrieved studies was evaluated using the Quality in Prognostic Studies tool. Also, current clinical practice guidelines from multiple international professional societies were reviewed.
RESULTS
We identified 60 prognostic studies, 69 case reports and case series, and eight international clinical practice guidelines. Our results demonstrated that most patients with ARDs were able to mount humoral and/or cellular responses after two doses of COVID-19 vaccine although this response was suboptimal in patients receiving certain disease-modifying medications including rituximab, methotrexate, mycophenolate mofetil, daily glucocorticoids >10 mg, abatacept, as well as in older individuals, and those with comorbid interstitial lung diseases. Safety reports on COVID-19 vaccines in patients with ARDs were largely reassuring with mostly self-limiting adverse events and very minimal post-vaccination disease flares.
CONCLUSION
Both types of the mRNA-vaccines and the AstraZeneca COVID-19 vaccines are highly effective and safe in patients with ARD. However, due to their suboptimal response in some patients, alternative mitigation strategies such as booster vaccines and shielding practices should also be followed. Management of immunomodulatory treatment regimens during the peri vaccination period should be individualized through shared decision making with patients and their attending rheumatologists.
Topics: Humans; Aged; COVID-19 Vaccines; RNA, Messenger; COVID-19; ChAdOx1 nCoV-19; Autoimmune Diseases; Rheumatic Diseases
PubMed: 37244811
DOI: 10.1016/j.vaccine.2023.05.048 -
Rheumatology International Jul 2017The aim is to systematically review the treatment for lupus nephritis (LN) by performing an overview of systematic reviews and meta-analyses. Electronic databases of... (Review)
Review
The aim is to systematically review the treatment for lupus nephritis (LN) by performing an overview of systematic reviews and meta-analyses. Electronic databases of OVID MEDLINE, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses investigating treatments for LN up to 13 July 2016. A measurement tool to assess systematic reviews (AMSTAR) was used to assess the quality of included studies. Totally, 24 studies were included. Of the eligible studies, 3 studies were rated as poor quality, 11 as moderate, and 10 as good. In LN induction therapy, comparing to cyclophosphamide, tacrolimus had higher complete remission rate, response rate, and anti-dsDNA negative conversion rate and led to lower risks of gastrointestinal symptoms and amenorrhea, and mycophenolate mofetil (MMF) was associated with higher response rate and less adverse events of leucopenia, alopecia, and ovarian failure. However, there was no difference in the efficacy and adverse events between tacrolimus and MMF. In LN maintenance therapy, the relapse rate and leucopenia rate were lower in MMF group than in azathioprine group, but there were no differences of end-stage kidney disease rate and mortality rate between the two groups. For LN induction therapy, both Tacrolimus and MMF are more effective and safer than cyclophosphamide, while there are no differences of efficacy or safety between the two treatments. For LN maintenance therapy, MMF seems to have less adverse events and lower relapse rate than azathioprine.
Topics: Disease Progression; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Lupus Nephritis; Meta-Analysis as Topic; Odds Ratio; Recurrence; Remission Induction; Risk Factors; Treatment Outcome
PubMed: 28493175
DOI: 10.1007/s00296-017-3733-2 -
Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
Systematic Reviews Sep 2016There is a lack of high-quality meta-analyses and network meta-analyses of immunosuppressive drugs for lupus nephritis. Our objective was to assess the comparative... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
There is a lack of high-quality meta-analyses and network meta-analyses of immunosuppressive drugs for lupus nephritis. Our objective was to assess the comparative benefits and harms of immunosuppressive drugs and corticosteroids in lupus nephritis.
METHODS
We conducted a systematic review and network meta-analysis (NMA) of trials of immunosuppressive drugs and corticosteroids in patients with lupus nephritis. We calculated odds ratios (OR) and 95 % credible intervals (CrI).
RESULTS
Sixty-five studies that met inclusion and exclusion criteria; data were analyzed for renal remission/response (37 trials; 2697 patients), renal relapse/flare (13 studies; 1108 patients), amenorrhea/ovarian failure (eight trials; 839 patients) and cytopenia (16 trials; 2257 patients). Cyclophosphamide [CYC] low dose (LD) and CYC high-dose (HD) were less likely than mycophenolate mofetil [MMF] and azathioprine [AZA], CYC LD, CYC HD and plasmapharesis less likely than cyclosporine [CSA] to achieve renal remission/response. Tacrolimus [TAC] was more likely than CYC LD to achieve renal remission/response. MMF and CYC were associated with a lower odds of renal relapse/flare compared to PRED and MMF was associated with a lower rate of renal relapse/flare than AZA. CYC was more likely than MMF and PRED to be associated with amenorrhea/ovarian failure. Compared to MMF, CYC, AZA, CYC LD, and CYC HD were associated with a higher risk of cytopenia.
CONCLUSIONS
In this systematic review and NMA, we found important differences between immunosuppressives used for the treatment of lupus nephritis. Patients and physicians can use this information for detailed informed consent in a patient-centered approach. Study limitations of between-study clinical heterogeneity and small sample size with type II error must be considered when interpreting these findings.
PROSPERO
CRD42016032965.
Topics: Adrenal Cortex Hormones; Clinical Trials as Topic; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Odds Ratio; Treatment Outcome
PubMed: 27619512
DOI: 10.1186/s13643-016-0328-z -
The Journal of Dermatological Treatment Feb 2018Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal... (Review)
Review
BACKGROUND
Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal guideline-recommended drug; omalizumab, has limited effect, side effects or is too expensive or unavailable. Herein, we systematically review the evidence for the use of the nonbiologic treatments in antihistamine-refractory chronic urticaria.
METHODS
We performed a systematic review of the literature using PubMed and Webofscience and identified studies that reported use of one or more of the nonbiological, nonantihistamine treatment options for chronic urticaria. The studies were evaluated based on study design, number of patients, effect of treatment and safety.
RESULTS
We identified 118 studies or case series with 13 different treatments (azathioprine, chloroquine, colchicine, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate, montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a paucity of controlled trials for most of the treatments reviewed albeit the strongest evidence in favor of a beneficial effect in chronic urticaria was, apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed by IVIG.
CONCLUSION
The treatment options reviewed should be seen as potential alternatives in treatment-resistant chronic urticaria where guideline-based selections have failed. However, larger controlled trials are warranted to advance the level of evidence, possibly supporting some treatments' future recommendation in selected patients.
Topics: Anti-Allergic Agents; Chronic Disease; Cyclosporine; Dapsone; Databases, Factual; Drug Resistance; Histamine Antagonists; Humans; Immunoglobulins, Intravenous; Plasmapheresis; Ultraviolet Therapy; Urticaria
PubMed: 28513247
DOI: 10.1080/09546634.2017.1329505 -
Zeitschrift Fur Rheumatologie Nov 2023The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment for lupus nephritis (LN).
METHODS
Meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety of tacrolimus and MMF as induction therapy for LN. We systematically reviewed RCTs and prospective cohort studies with a tacrolimus dose of 3 mg daily and performed a meta-analysis of the efficacy and safety of tacrolimus as an induction treatment for LN in comparison to MMF.
RESULTS
The inclusion criteria were satisfied by eight studies (five RCTs and three prospective cohort studies) with a total of 408 individuals (289 for tacrolimus vs. MMF and 119 for low-dose tacrolimus). Tacrolimus and MMF had similar complete remission rates (odds ratio [OR] 1.028; 95% confidence interval [CI] 0.589-1.796; p = 0.922). The partial remission rate did not differ between the tacrolimus and MMF groups (OR 1.400; 95% CI 0.741-2.646; p = 0.300). Tacrolimus and MMF showed no differences in proteinuria, serum albumin, serum creatinine, creatinine clearance, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or extra-renal SLEDAI. The incidence of infection, severe infection, leukopenia, and hyperglycemia did not differ between the tacrolimus and MMF groups. However, herpes zoster infection was significantly less common in the tacrolimus group (OR 0.137; 95% CI 0.034-0.546; p = 0.005), whereas serum creatinine elevation was significantly higher in the tacrolimus group than in the MMF group (OR 8.148; 95% CI 1.369-48.50; p = 0.021). At 3 mg/d, tacrolimus was shown to be safe, well tolerated, and offered therapeutic benefits in all investigations.
CONCLUSION
Tacrolimus was comparable to MMF in terms of effectiveness and safety as an induction therapy for LN, with the exception of a reduced risk of herpes zoster infection and a rise in serum creatinine. In individuals with LN, 3 mg/d tacrolimus was proven to be efficacious and safe.
Topics: Humans; Tacrolimus; Lupus Nephritis; Mycophenolic Acid; Immunosuppressive Agents; Cyclophosphamide; Creatinine; Treatment Outcome; Herpes Zoster
PubMed: 36607421
DOI: 10.1007/s00393-022-01313-2