-
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
Journal of Nephrology Mar 2023Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare condition characterised by bilateral uveitis and interstitial nephritis. There is no nationally, or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare condition characterised by bilateral uveitis and interstitial nephritis. There is no nationally, or internationally agreed upon treatment regimen. A systematic review was undertaken to report the renal outcomes in TINU, and treatments used.
METHODS
Medline (1969-2021) and EMBASE (1988-2021) databases were searched for primary studies, clinical practice guidelines and case reports of adult and paediatric TINU cases, as defined by Mandeville criteria. Two reviewers identified articles meeting inclusion criteria (registered with PROSPERO). Data were extracted into a synthesis table and meta-analysis performed. Quality of case series was also assessed.
RESULTS
One hundred twenty-two articles were identified, totalling 257 cases included in the meta-analysis. Females were more commonly affected than males (2:1), and median age was 19 years. GFR at follow-up correlated with nadir GFR, and the proportion with GFR <90 ml/min/1.73 m was statistically different between adult and paediatric groups. Of the entire cohort, 40% had GFR <90 ml/min/1.73 m at follow-up. Glucocorticoid monotherapy was the most common treatment (70%); other strategies included no treatment (9%) and immunosuppressant drugs (e.g. azathioprine), mostly in steroid-resistant cases, or as 'steroid-sparing' alternatives.
CONCLUSIONS
The majority of literature regarding TINU is limited to case reports and case series. There are no prospective trials assessing the effects of different treatments on renal outcomes, and currently employed treatment strategies are physician-specific without a reliable evidence-base. Prospective data collection as part of multicentre trials should be a research focus to improve the evidence-base.
Topics: Male; Adult; Female; Humans; Child; Young Adult; Nephritis, Interstitial; Kidney; Uveitis; Glucocorticoids
PubMed: 36396848
DOI: 10.1007/s40620-022-01478-8 -
Rheumatology International Dec 2022We aimed to summarise effects and use of non-pharmacological and pharmacological treatments for sarcoidosis with musculoskeletal manifestations. We systematically... (Review)
Review
We aimed to summarise effects and use of non-pharmacological and pharmacological treatments for sarcoidosis with musculoskeletal manifestations. We systematically searched the Cochrane Library, Ovid MEDLINE, Embase, CINAHL, AMED, Scopus, clinical.trials.gov, PROSPERO and PEDro for systematic reviews from 2014 to 2022 and for primary studies from date of inception to March 29, 2022, and studies with patients diagnosed with sarcoidosis with musculoskeletal manifestations. Inclusion criteria required that studies reported effects of non-pharmacological and/or pharmacological treatments or number of patients receiving these treatments. Results were reported narratively and in forest plots. Eleven studies were included. No systematic reviews fulfilled our inclusion criteria. None of the included studies had a control group. We found that between 23 and 100% received corticosteroids, 0-100% received NSAIDs, 5-100% received hydroxychloroquine, 12-100% received methotrexate, 0-100% received TNF inhibitors, and 3-4% received azathioprine. Only ten patients in one study had used non-pharmacological treatments, including occupational therapy, chiropractic and acupuncture. There are no controlled studies on treatment effects for patients with sarcoidosis with musculoskeletal manifestations. We found 11 studies reporting use of pharmacological treatments and only one study reporting use of non-pharmacological treatments. Our study identified major research gaps for pharmacological and non-pharmacological treatment in musculoskeletal sarcoidosis and warrant randomised clinical trials for both.
Topics: Humans; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Hydroxychloroquine; Methotrexate; Sarcoidosis; Tumor Necrosis Factor Inhibitors
PubMed: 35943526
DOI: 10.1007/s00296-022-05171-8 -
Therapeutic Drug Monitoring Oct 2021The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in clinical practice is heterogeneous. This systematic review and meta-analysis aimed to compare the mean concentration of TM between patients in biochemical remission and those not in remission.
METHODS
A systematic literature search was conducted using PubMed, Scopus, the Cochrane Library, and Google Scholar for keywords related to TM and AIH. Two reviewers independently searched and selected studies comparing the levels of 6-methyl mercaptopurine (6-MMP) and 6-thioguanine nucleotide (6-TGN) and their ratio in cases of AIH in remission and otherwise. Meta-analysis was performed by calculating the weighted mean difference using the inverse variance heterogeneity model.
RESULTS
A total of 1066 records were identified through systematic search; of which, 7 (n = 3 pediatric, n = 4 adults) were considered for inclusion, and 442 TM measurements (n = 128 in children) were analyzed. Mean 6-TGN levels were significantly higher among patients in remission than in those who were not, with a pooled weighted mean difference (WMD) of 15.67 [95% confidence interval (CI), 6.68-24.66] pmol/8 × 108 red blood cells (RBC). The difference was higher in the pediatric age group (WMD, 56.11; 95% CI, 13.60-98.62) than in adults (WMD, 13.77; 95% CI, 4.58-22.97). There was no significant difference in the 6-MMP levels (WMD, -431.7; 95% CI, -1237.4 to 373.9 pmol/8 × 108 RBC; I2 = 82%; n = 3 studies) or 6-MMP/6-TGN ratio among the patients who were in biochemical remission and those who were not (WMD, -0.97; 95% CI, -5.77 to 3.84; I2 = 82%; n = 3 studies).
CONCLUSIONS
This meta-analysis suggests a link between 6-TGN levels and biochemical remission in AIH. Further high-quality studies are required to determine the therapeutic cutoff of 6-TGN.
Topics: Adult; Azathioprine; Child; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mercaptopurine; Thioguanine
PubMed: 33346628
DOI: 10.1097/FTD.0000000000000848 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
BMJ Clinical Evidence Feb 2012Multiple sclerosis is the most common cause of neurological disability in young adults. Irreversible disability can occur, but life expectancy is generally not affected. (Review)
Review
INTRODUCTION
Multiple sclerosis is the most common cause of neurological disability in young adults. Irreversible disability can occur, but life expectancy is generally not affected.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions aimed at reducing relapse rates and disability in people with multiple sclerosis? What are the effects of interventions to improve symptoms during acute relapse? What are the effects of treatments for fatigue, spasticity, and multidisciplinary care on disability in people with multiple sclerosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 71 systematic reviews, RCTs, and observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following key interventions: amantadine, azathioprine, behaviour modification, botulinum toxin, corticosteroids, exercise, gabapentin, inpatient or outpatient rehabilitation, interferon beta, intrathecal baclofen, intravenous immunoglobulin, methotrexate, mitoxantrone, modafinil, natalizumab, oral drug treatments, parenteral glatiramer acetate, physiotherapy, and plasma exchange.
Topics: Acute Disease; Administration, Oral; Humans; Life Expectancy; Multiple Sclerosis; Plasma Exchange; Plasmapheresis; Sex Factors
PubMed: 22321967
DOI: No ID Found -
The Cochrane Database of Systematic... May 2016Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial.
OBJECTIVES
To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis.
SEARCH METHODS
The MEDLINE, EMBASE and Cochrane Library databases were searched from inception to 30 July 2015. Both full randomized controlled trials and associated abstracts were included.
SELECTION CRITERIA
Randomized controlled trials of at least 12 months duration that compared azathioprine or 6-mercaptopurine with placebo or standard maintenance therapy (e.g. mesalazine) were included.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data using standard forms. Disagreements were solved by consensus including a third author. Study quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to maintain clinical or endoscopic remission. Secondary outcomes included adverse events and withdrawal due to adverse events. Analyses were performed separately by type of control (placebo, or active comparator). Pooled risk ratios were calculated based on the fixed-effect model unless heterogeneity was shown. The GRADE approach was used to assess the overall quality of evidence for pooled outcomes.
MAIN RESULTS
Seven studies including 302 patients with ulcerative colitis were included in the review. The risk of bias was high in three of the studies due to lack of blinding. Azathioprine was shown to be significantly superior to placebo for maintenance of remission. Fourty-four per cent (51/115) of azathioprine patients failed to maintain remission compared to 65% (76/117) of placebo patients (4 studies, 232 patients; RR 0.68, 95% CI 0.54 to 0.86). A GRADE analysis rated the overall quality of the evidence for this outcome as low due to risk of bias and imprecision (sparse data). Two trials that compared 6-mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity and thus were not pooled. Fifty per cent (7/14) of 6-mercaptopurine patients failed to maintain remission compared to 100% (8/8) of mesalazine patients (1 study, 22 patients; RR 0.53, 95% CI 0.31 to 0.90). Fifty-eight per cent (7/12) of azathioprine patients failed to maintain remission compared to 38% (5/13) of sulfasalazine patients (1 study, 25 patients; RR 1.52, 95% CI 0.66 to 3.50). One small study found that 6-mercaptopurine was superior to methotrexate for maintenance of remission. In the study, 50% (7/14) of 6-mercaptopurine patients and 92% (11/12) of methotrexate patients failed to maintain remission (1 study, 26 patients; RR 0.55, 95% CI 0.31 to 0.95). One very small study compared azathioprine with cyclosporin and found that there was no significant difference between patients failing remission on azathioprine (50%, 4/8) or cyclosporin (62.5%, 5/8) (1 study, 16 patients, RR 0.80 95% CI 0.33 to 1.92). When placebo-controlled studies were pooled with aminosalicylate-comparator studies to assess adverse events, there was no statistically significant difference between azathioprine and control in the incidence of adverse events. Nine per cent (11/127) of azathioprine patients experienced at least one adverse event compared to 2% (3/130) of placebo patients (5 studies, 257 patients; RR 2.82, 95% CI 0.99 to 8.01). Patients receiving azathioprine were at significantly increased risk of withdrawing due to adverse events. Eight per cent (8/101) of azathioprine patients withdrew due to adverse events compared to 0% (0/98) of control patients (5 studies, 199 patients; RR 5.43, 95% CI 1.02 to 28.75). Adverse events related to study medication included acute pancreatitis (3 cases, plus 1 case on cyclosporin) and significant bone marrow suppression (5 cases). Deaths, opportunistic infection or neoplasia were not reported.
AUTHORS' CONCLUSIONS
Azathioprine therapy appears to be more effective than placebo for maintenance of remission in ulcerative colitis. Azathioprine or 6-mercaptopurine may be effective as maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine. This review updates the existing review of azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis which was published in the Cochrane Library (September 2012).
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites; Azathioprine; Colitis, Ulcerative; Humans; Maintenance Chemotherapy; Mercaptopurine; Mesalamine; Randomized Controlled Trials as Topic; Secondary Prevention; Sulfasalazine
PubMed: 27192092
DOI: 10.1002/14651858.CD000478.pub4 -
Innovations in Clinical Neuroscience 2022Neuromyelitis optica spectrum disorder (NMOSD) is a neurological condition consisting of relapse-related disability. Treatment options are limited. This systematic... (Review)
Review
Comparative Analysis of Treatment Outcomes in Patients with Neuromyelitis Optica Spectrum Disorder Treated with Rituximab, Azathioprine, and Mycophenolate Mofetil: A Systematic Review and Meta-analysis.
INTRODUCTION
Neuromyelitis optica spectrum disorder (NMOSD) is a neurological condition consisting of relapse-related disability. Treatment options are limited. This systematic review and meta-analysis aimed to evaluate the effectiveness and tolerability of rituximab (RTX) in comparison to azathioprine (AZT) and mycophenolate mofetil (MMF) for the treatment of NMOSD.
METHODS
A systematic search was conducted among electronic databases, including PubMed, Scopus, EBSCO, and Cochrane, for relevant studies. We included randomized, controlled trials and prospective and retrospective studies evaluating the efficacy and safety of RTX compared to AZT and/or MMF in adult and pediatric patients with NMOSD. The Newcastle-Ottawa Scale (NOS) and Cochrane Collaboration tool were used to determine the risk of bias.
RESULTS
Eleven studies involving 1,086 patients were included in our study. Treatment with RTX generally yielded favorable annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) results in comparison to AZT and MMF, despite its variable statistical significance. RTX treatment reduced the relapse rate and hazard risk for relapse (HRR). Patients in the RTX group experienced significantly fewer adverse events, among which the most common were allergies, infections, and leukopenia.
CONCLUSION
In this study, RTX appeared to be superior to AZT and MMF in improving disability and reducing relapse in patients with NMOSD. RTX is also associated with fewer adverse events based on pooled analysis. Future randomized clinical trials are needed to establish the efficacy and safety of RTX in patients with NMOSD.
PubMed: 35958974
DOI: No ID Found -
International Journal of Molecular... Apr 2021Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has... (Meta-Analysis)
Meta-Analysis Review
Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the , , , , and genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.
Topics: Azathioprine; Cyclosporine; Humans; Pharmacogenomic Testing; Pharmacogenomic Variants; Polymorphism, Genetic; Prednisolone; Renal Insufficiency, Chronic; Tacrolimus; Treatment Outcome
PubMed: 33923087
DOI: 10.3390/ijms22094480 -
Autoimmunity Reviews Apr 2022Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as well as medications exposure might impair gonadal function.
OBJECTIVE
This systematic literature review (SLR) aimed to explore clinical, hormonal, serological and treatment factors associated with fertility outcomes in women of childbearing age with SLE.
METHODS
This SLR was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English (1972 - 30th April 2021) in Pubmed, EMBASE, Scopus and Cochrane Library were screened. Studies selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. The risk of bias of the included studies was assessed using the NIH risk-of-bias tool.
RESULTS
Of 789 abstracts evaluated, we included in this review 46 studies, of which 1 SLR, 16 cross-sectional studies, 18 cohort studies, 10 observational studies and 1 case-series, with data pertaining to 4704 patients (mean age 31.5 ± 3.7 years, disease duration 83.27 ± 38.3 months). Definitions of premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered and the age of onset of amenorrhea. Clinical factors associated with the development of POF were older age at the time of initiation of therapy, and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and POF, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids associated with a lower risk of POF compared to CYC. POF was less frequent in patients co-treated with CYC and gonadotropin-releasing hormone analogues (GnRH-a) compared with patients not receiving GnRH-a (risk ratio 0.28, 95%-CI [0.14; 0.55]). 11 studies evaluated the impact of damage accrual and disease activity on ovarian reserve with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors and, among others, neither anti-Müllerian Hormone nor anti-corpus luteum antibodies were associated with POF.
CONCLUSION
The strongest evidence regarding management factors associated with fertility in SLE women of childbearing age remains the treatment with CYC, as well as its cumulative dosage. Hormonal and serological factors appeared not to impact fertility outcomes, but they might be used as a surrogate of fertility, especially during the treatment with disease-specific drugs.
Topics: Adult; Cross-Sectional Studies; Cyclophosphamide; Female; Fertility; Humans; Lupus Erythematosus, Systemic; Primary Ovarian Insufficiency
PubMed: 34995765
DOI: 10.1016/j.autrev.2022.103038