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The Cochrane Database of Systematic... Mar 2020IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a Cochrane review first published in 2003 and updated in 2015.
OBJECTIVES
To determine the benefits and harms of immunosuppression strategies for the treatment of IgA nephropathy.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 9 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the 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
We included randomised controlled trials (RCTs) and quasi-RCTs of treatment for IgA nephropathy in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study risk of bias and extracted data. Estimates of treatment effect were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Risks of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE methodology.
MAIN RESULTS
Fifty-eight studies involving 3933 randomised participants were included. Six studies involving children were eligible. Disease characteristics (kidney function and level of proteinuria) were heterogeneous across studies. Studies evaluating steroid therapy generally included patients with protein excretion of 1 g/day or more. Risk of bias within the included studies was generally high or unclear for many of the assessed methodological domains. In patients with IgA nephropathy and proteinuria > 1 g/day, steroid therapy given for generally two to four months with a tapering course probably prevents the progression to ESKD compared to placebo or standard care (8 studies; 741 participants: RR 0.39, 95% CI 0.23 to 0.65; moderate certainty evidence). Steroid therapy may induce complete remission (4 studies, 305 participants: RR 1.76, 95% CI 1.03 to 3.01; low certainty evidence), prevent doubling of serum creatinine (SCr) (7 studies, 404 participants: RR 0.43, 95% CI 0.29 to 0.65; low certainty evidence), and may lower urinary protein excretion (10 studies, 705 participants: MD -0.58 g/24 h, 95% CI -0.84 to -0.33;low certainty evidence). Steroid therapy had uncertain effects on glomerular filtration rate (GFR), death, infection and malignancy. The risk of adverse events with steroid therapy was uncertain due to heterogeneity in the type of steroid treatment used and the rarity of events. Cytotoxic agents (azathioprine (AZA) or cyclophosphamide (CPA) alone or with concomitant steroid therapy had uncertain effects on ESKD (7 studies, 463 participants: RR 0.63, 95% CI 0.33 to 1.20; low certainty evidence), complete remission (5 studies; 381 participants: RR 1.47, 95% CI 0.94 to 2.30; very low certainty evidence), GFR (any measure), and protein excretion. Doubling of serum creatinine was not reported. Mycophenolate mofetil (MMF) had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, infection, and malignancy. Death was not reported. Calcineurin inhibitors compared with placebo or standard care had uncertain effects on complete remission, SCr, GFR, protein excretion, infection, and malignancy. ESKD and death were not reported. Mizoribine administered with renin-angiotensin system inhibitor treatment had uncertain effects on progression to ESKD, complete remission, GFR, protein excretion, infection, and malignancy. Death and SCr were not reported. Leflunomide followed by a tapering course with oral prednisone compared to prednisone had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, and infection. Death and malignancy were not reported. Effects of other immunosuppressive regimens (including steroid plus non-immunosuppressive agents or mTOR inhibitors) were inconclusive primarily due to insufficient data from the individual studies in low or very low certainty evidence. The effects of treatments on death, malignancy, reduction in GFR at least of 25% and adverse events were very uncertain. Subgroup analyses to determine the impact of specific patient characteristics such as ethnicity or disease severity on treatment effectiveness were not possible.
AUTHORS' CONCLUSIONS
In moderate certainty evidence, corticosteroid therapy probably prevents decline in GFR or doubling of SCr in adults and children with IgA nephropathy and proteinuria. Evidence for treatment effects of immunosuppressive agents on death, infection, and malignancy is generally sparse or low-quality. Steroid therapy has uncertain adverse effects due to a paucity of studies. Available studies are few, small, have high risk of bias and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible due to a lack of studies. There is no evidence that other immunosuppressive agents including CPA, AZA, or MMF improve clinical outcomes in IgA nephropathy.
Topics: Adult; Calcineurin Inhibitors; Cause of Death; Child; Confidence Intervals; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Leflunomide; Mycophenolic Acid; Proteinuria; Randomized Controlled Trials as Topic; Remission Induction; Ribonucleosides; Risk; Steroids
PubMed: 32162319
DOI: 10.1002/14651858.CD003965.pub3 -
Journal of Endocrinological... Jun 2020The dual antiproliferative mechanism of mycophenolate appears to be beneficial in Graves' orbitopathy (GO). (Meta-Analysis)
Meta-Analysis
PURPOSE
The dual antiproliferative mechanism of mycophenolate appears to be beneficial in Graves' orbitopathy (GO).
METHODS
Safety data from the two published mycophenolate trials and the original database of the European Group on Graves' Orbitopathy (EUGOGO) trial were systematically analyzed. Treatment efficacy stratified by individual visual parameters of activity and severity were compared.
RESULTS
A total of 129 adverse events (AE) involving 50 patients (29.4%) were noted among all mycophenolate-treated patients. Mycophenolate sodium plus intravenous glucocorticoid (MPS + GC) group of the EUGOGO trial recorded significantly more AE (55.4% versus 4.6% of patients affected) and serious adverse events (SAE) (12.5% versus 0%) than mycophenolate mofetil (MMF) group of the Chinese trial. None of those SAE was side effect (SE). Most SE in MPS + GC group were mild. Gastrointestinal disorders, infection and liver dysfunction affected 8.8%, 7.1% and 1.2% of all mycophenolate-treated patients (versus 5.4%, 5.4% and 1.2% of all patients on GC monotherapy, respectively). MPS + GC did not significantly increase the risk of infection or liver dysfunction when compared to GC monotherapy. No cytopenia, serious infection or treatment-related mortality was reported. The much higher AE rates of mycophenolate trials in other autoimmune diseases or transplantations suggested that major mycophenolate toxicities were mostly dose- and duration dependent. Mycophenolate, either as monotherapy or as combination, achieved better overall response than GC monotherapy.
CONCLUSION
The risk-benefit ratio of low-dose mycophenolate treatment in active moderate-to-severe GO is highly favorable given its reassuring safety profile with low rate of mild-to-moderate SE and promising efficacy.
Topics: Antibiotics, Antineoplastic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Gastrointestinal Diseases; Glucocorticoids; Graves Ophthalmopathy; Humans; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 31834613
DOI: 10.1007/s40618-019-01161-z -
Journal of Comparative Effectiveness... Oct 2019Therapy for lupus nephritis (LN) requires treatment with immunosuppressive regimens, often including intravenous cyclophosphamide (IVCY), mycophenolate mofetil (MMF) or... (Meta-Analysis)
Meta-Analysis
Therapy for lupus nephritis (LN) requires treatment with immunosuppressive regimens, often including intravenous cyclophosphamide (IVCY), mycophenolate mofetil (MMF) or azathioprine. Additionally, tacrolimus (original form or generic) is recommended to treat LN patients in Asia, including China. However, the cost-effectiveness of tacrolimus therapy has not previously been assessed. We aimed to estimate the cost-effectiveness of tacrolimus in the treatment of moderate-to-severe LN versus standard therapies in China. This cost-effectiveness model combined a decision-tree/Markov-model structure to map transitions between health states during induction and maintenance treatment phases. Induction with tacrolimus, IVCY or MMF, was followed by tacrolimus, MMF or azathioprine maintenance. According to the model, during induction, complete remission rates were higher with tacrolimus versus IVCY (relative risk 1.40 vs IVCY [deterministic sensitivity analysis minimum 0.92, maximum 2.13]) and time to response was shorter. Relapse rates were lower with tacrolimus versus azathioprine or MMF during maintenance. Tacrolimus induction and maintenance was the most cost-effective regimen, incurring the lowest total costs (CN¥180,448) with the highest quality-adjusted life-years. The model demonstrated that tacrolimus use in both induction and maintenance therapy may be an efficacious and cost-effective treatment for LN in China.
Topics: Azathioprine; China; Cost-Benefit Analysis; Cyclophosphamide; Health Expenditures; Humans; Immunosuppressive Agents; Lupus Nephritis; Markov Chains; Mycophenolic Acid; Network Meta-Analysis; Quality-Adjusted Life Years; Recurrence; Remission Induction; Severity of Illness Index; Tacrolimus; Treatment Outcome
PubMed: 31580156
DOI: 10.2217/cer-2018-0111 -
Immunosuppressive treatment for peripheral neuropathies in Sjogren's syndrome - a systematic review.Romanian Journal of Internal Medicine =... Mar 2020Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no...
BACKGROUND
Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no consensus about peripheral neuropathy treatment in SS. Our aim is to identify studies proving the efficiency of immunosuppressive treatment on peripheral neuropathies in SS.
METHODS
The search was conducted on the PubMed (MEDLINE) database. Studies with patients diagnosed with SS and peripheral neuropathy were included. Treatment with one of the following was among inclusion criteria: glucocorticoids (GC), rituximab (RTX), azathioprine (AZA), mycophenolic acid (MMF), cyclophosphamide (CP), methotrexate (MTX), plasmapheresis or iv immunoglobulins (IV IG).
RESULTS
A total of 116 results were found and abstracts were examined. 103 papers were excluded, and the remaining 13 papers were analyzed. They were 3 case series and 10 case reports, retrospective, totalizing 62 patients of which 22 (35.5%) received IV IG, 8 (13%) received RTX, 7 (11%) CP, and 5 (8%) received only GC. Drug associations containing corticosteroids were frequent. Of those 22 treated with IV IG, 18 patients improved (82%), and 4 stabilized (18%). IV IG was useful in sensory, motor and sensorimotor neuropathies. CP had good results in mononeuritis multiplex, while autonomic neuropathies responded well to GC or RTX. AZA, RTX, MTX, MMF or plasmapheresis were not used alone. Follow-up periods were heterogenous and the evaluation of the neuropathy was not systematic.
CONCLUSION
There is only low level evidence (retrospective case reports and case series). In most cases, IV IG treatment in patients with peripheral neuropathies and SS resulted in clinical improvement, while other therapies, such as RTX, corticosteroids and CP proved to be useful in a handful of cases.
Topics: Adrenal Cortex Hormones; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Peripheral Nervous System Diseases; Rituximab; Sjogren's Syndrome
PubMed: 31527298
DOI: 10.2478/rjim-2019-0022 -
Rheumatology (Oxford, England) Apr 2020To assess the safety and efficacy of glucocorticoids (GCs), immunosuppressive agents (IM) and rituximab (RTX), alone or in combination, for the treatment of IgG4-RD. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the safety and efficacy of glucocorticoids (GCs), immunosuppressive agents (IM) and rituximab (RTX), alone or in combination, for the treatment of IgG4-RD.
METHODS
Relevant articles published were searched in the databases with relevant key words. Network meta-analysis was conducted, with various outcomes including relapse rate, remission rate and adverse events. Data were calculated with odds ratio (ORs) and 95% CI. P-score was used to rank the treatments.
RESULTS
A total of 15 studies involving 1169 patients were included. Network meta-analysis indicated that RTX maintenance therapy had the lowest relapse rate of all treatments (OR = 0.10, 95% CI [0.01, 1.63]), whereas GCs + IM was associated with a lower relapse rate compared with GCs alone (OR = 0.39, 95% CI [0.20, 0.80]). Further, patients treated with GCs + IM had a higher remission rate than those given GCs (OR= 3.36, 95% CI [1.44, 7.83]), IM (OR= 55.31, 95% CI [13.73, 222.73]) monotherapies or RTX induction therapy only (OR= 7.38, 95% CI [1.56, 34.94]). The rate of adverse events was comparable among the different treatment groups.
CONCLUSION
Treatment of IgG4-RD patients with GCs and IM was associated with higher remission rates and lower relapse rates, as well as comparable safety profiles compared with GC, IM and RTX induction therapy. RTX maintenance therapy had a larger reduction in the relapse rate compared with GC and IM. The current evidence should be carefully scrutinized as the included studies were observational in design. Larger randomized controlled trials are needed to confirm.
Topics: Antirheumatic Agents; Azathioprine; Cyclophosphamide; Cyclosporine; Drug Therapy, Combination; Glucocorticoids; Humans; Immunoglobulin G4-Related Disease; Immunosuppressive Agents; Maintenance Chemotherapy; Mercaptopurine; Methotrexate; Mycophenolic Acid; Network Meta-Analysis; Odds Ratio; Recurrence; Remission Induction; Rituximab; Tacrolimus
PubMed: 31511884
DOI: 10.1093/rheumatology/kez380 -
Transplantation Oct 2019The current standard of care immunosuppressive regimen in kidney transplantation (KT) includes a combination of mycophenolates (MMF/MPA) with a calcineurin inhibitor... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The current standard of care immunosuppressive regimen in kidney transplantation (KT) includes a combination of mycophenolates (MMF/MPA) with a calcineurin inhibitor (CNI).
METHODS
We designed a systematic review including all randomized clinical trials (RCTs) assessing the outcomes in KT recipients receiving mTORi + CNI compared with regimens containing MMF/MPA or azathioprine with CNI.
RESULTS
A total of 24 studies with 7356 participants were included. The comparison between mTORi-CNI and MMF/MPA-CNI did not show differences in acute rejection, mortality, or graft loss rates. Better graft function was observed using MMF/MPA-CNI than using mTORi + CNI, but this difference was not evident when the mTORi was associated with reduced dose CNI in more recent studies with everolimus. Dyslipidemia, lymphoceles, and impaired wound healing were more frequent with mTORi-CNI and diarrhea and leukopenia were more frequent with MMF/MPA-CNI. Viral infections at any time and malignant neoplasia beyond 2 years were less frequent with mTORi-CNI. Rates of discontinuation because of adverse effects in the mTORi groups varied between 17% and 46% compared to 0%-26.6% in MMF/MPA groups. The current use of lower mTORi dosage has decreased the discontinuation rates.
CONCLUSIONS
Efficacy is similar with mTORi + CNI and MMF/MPA-CNI. The safety profile is the predominant difference between the 2 regimens.
Topics: Calcineurin Inhibitors; Diarrhea; Drug Therapy, Combination; Dyslipidemias; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Randomized Controlled Trials as Topic; Standard of Care; TOR Serine-Threonine Kinases; Treatment Outcome
PubMed: 31343574
DOI: 10.1097/TP.0000000000002769 -
The Journal of Dermatological Treatment Dec 2020For severe cases of atopic dermatitis, systemic or potent agents may be required for control of disease. There have been some reports of treatment efficacy of off-label... (Meta-Analysis)
Meta-Analysis
For severe cases of atopic dermatitis, systemic or potent agents may be required for control of disease. There have been some reports of treatment efficacy of off-label use of mycophenolate mofetil (MMF) in patients with refractory atopic dermatitis or have developed adverse effects to initial systemic agents. Electronic searches were performed using six databases from their inception to April 2019. Data were extracted and analyzed according to predefined clinical endpoints. From 140 cases, the mean age was 38.21 ± 22.8 years. There were 52.9% males and 47.1% females. The average number of failed agents was 3.5 ± 1.2. 77.6% reported partial or full remission. Relapses occurred in 8.2% of cases. The average time for initial effects was 6.8 ± 7 weeks. There was a significant reduction in pre to post SCORAD scores by 18 points ( = .0002). More males had complications compared to females. Prolonged duration of treatment ≥1 year was associated with herpes infections. In summary, the current evidence to date is low-quality in nature but is promising regarding the efficacy and safety of MMF for adult and pediatric atopic dermatitis. There should be ongoing monitoring for infections that may develop on long term therapy.
Topics: Adolescent; Adult; Analysis of Variance; Dermatitis, Atopic; Enzyme Inhibitors; Female; Humans; IMP Dehydrogenase; Male; Mycophenolic Acid; Off-Label Use; Remission Induction
PubMed: 31294617
DOI: 10.1080/09546634.2019.1642996 -
World Journal of Gastroenterology Mar 2019Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease (MS-IBD). This study hypothesized that...
BACKGROUND
Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease (MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.
AIM
To investigate the effectiveness of conventional therapy for MS-IBD.
METHODS
A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Corticosteroids (prednisone, hydrocortisone, budesonide, prednisolone, dexamethasone), 5-aminosalicylic acid (5-ASA) derivatives (mesalazine and sulfasalazine) and immunosuppressants [azathioprine (AZA), methotrexate (MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine (6-MP)] were considered conventional therapy. The exclusion criteria were sample size below 50; narrative reviews; specific subpopulations (., pregnant women, comorbidities); studies on postoperative IBD; and languages other than English, Spanish, French or Portuguese. The primary outcome measures were clinical remission (induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.
RESULTS
The search strategy identified 1995 citations, of which 27 were considered eligible (7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected (AZA and 6-MP showed no advantage over placebo, MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials (RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing, one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.
CONCLUSION
High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Crohn Disease; Feces; Glucocorticoids; Humans; Immunosuppressive Agents; Intestinal Mucosa; Leukocyte L1 Antigen Complex; Remission Induction; Severity of Illness Index; Treatment Outcome
PubMed: 30863001
DOI: 10.3748/wjg.v25.i9.1142 -
Swiss Medical Weekly Feb 2019Ocular inflammations such as uveitis and scleritis can lead to significant visual impairment if not treated properly. To limit potentially sight-threatening...
Ocular inflammations such as uveitis and scleritis can lead to significant visual impairment if not treated properly. To limit potentially sight-threatening complications, good control of the inflammation in the acute phase is necessary. Corticosteroids have been the mainstay of ocular therapies for many years, but high doses of corticosteroids, which are required to maintain quiescence in severe uveitis, can be associated with many systemic and ocular complications. In order to limit steroid side-effects, classic immunosuppressant and immunobiologic agents have been widely used as steroid-sparing agents. In this review, we summarise the immunosuppressive drug therapy utilised in the treatment of ocular inflammatory diseases.
Topics: Adrenal Cortex Hormones; Azathioprine; Cyclosporine; Enzyme Inhibitors; Immunosuppressive Agents; Methotrexate; Mycophenolic Acid; Scleritis; Uveitis
PubMed: 30852832
DOI: 10.4414/smw.2019.20025 -
Alimentary Pharmacology & Therapeutics Apr 2019First-line treatment for autoimmune hepatitis (AIH) typically includes corticosteroids in combination with azathioprine. Mycophenolate mofetil (MMF) is often used as a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
First-line treatment for autoimmune hepatitis (AIH) typically includes corticosteroids in combination with azathioprine. Mycophenolate mofetil (MMF) is often used as a rescue therapy in patients who are intolerant of, or nonresponsive to, standard therapy.
AIM
To systematically review studies and perform a meta-analysis on the efficacy and safety of MMF as a second-line therapy for AIH patients.
METHODS
MEDLINE, EMBASE and Cochrane Central were searched for studies that reported data on efficacy and safety of MMF as a second-line therapy in AIH. We calculated the pooled response rate, adverse events rate and discontinuation rate due to side effects, with their corresponding 95% confidence intervals.
RESULTS
Twelve studies comprising 397 patients, followed for a median of 34 months (range, 12-47 months), were included. MMF doses ranged from 0.5-4.0 g/d. Pooled response rate was 0.58 (95% CI 0.54-0.63). Pooled adverse events rate was 0.14 (95% CI 0.11-0.17), and pooled discontinuation rate due to side effects was 0.08 (95% CI 0.06-0.11). Five studies (n = 309) specified response rates according to reason for using MMF. Pooled response rate in the subgroup with intolerance to standard therapy was 0.82 (95% CI 0.77-0.87) and pooled response rate among nonresponders was 0.32 (95% CI 0.24-0.39).
CONCLUSIONS
The overall efficacy of MMF as second-line therapy in AIH was high. Response rate was greater in patients who started the medication due to intolerance to standard therapy as opposed to nonresponse. Overall, MMF was well tolerated, with a low discontinuation rate due to side effects.
Topics: Antibiotics, Antineoplastic; Azathioprine; Drug-Related Side Effects and Adverse Reactions; Female; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Treatment Outcome
PubMed: 30761563
DOI: 10.1111/apt.15157