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Journal of Clinical Neuroscience :... Jun 2021Treatments of myasthenia gravis (MG) usually include immunosuppressants such as glucocorticoids, tacrolimus, and azathioprine (AZA). In clinical practice, azathioprine... (Meta-Analysis)
Meta-Analysis
Treatments of myasthenia gravis (MG) usually include immunosuppressants such as glucocorticoids, tacrolimus, and azathioprine (AZA). In clinical practice, azathioprine therapy is thought to have a potential risk for developing secondary malignancies in myasthenia gravis patients. However, published data on the long-term safety of azathioprine in myasthenia gravis patients are limited and not consistent among studies. To explore cancer occurrence following azathioprine therapy in myasthenia gravis patients in the long term, we searched Medline, EMBASE, and the Cochrane Library for terms related to azathioprine, myasthenia gravis and cancer occurrence. Two investigators independently extracted trial data. A pooled estimate was calculated from fixed-effects meta-analysis. Our analysis included 1650 azathioprine-treated patients and 2481 non-azathioprine-treated patients. All five studies showed some concerns regarding the risk of bias. In a meta-analysis of 5 studies, we observed no significantly elevated risk of cancer occurrence among individuals with prior myasthenia gravis diagnosis who received long-term azathioprine treatment (OR 1.09; 95% CI 0.86-1.38, p = 0.46). Prospective studies are needed to observe the safety of azathioprine.
Topics: Azathioprine; Humans; Immunosuppressive Agents; Myasthenia Gravis; Neoplasms; Prospective Studies
PubMed: 33992207
DOI: 10.1016/j.jocn.2021.03.015 -
Renal Failure 2023This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).
METHODS
A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.
RESULTS
The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.
CONCLUSIONS
Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.
Topics: Humans; Lupus Nephritis; Cyclophosphamide; Induction Chemotherapy; Network Meta-Analysis; Treatment Outcome; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 38087473
DOI: 10.1080/0886022X.2023.2290365 -
Modern Rheumatology Aug 2023The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis for 2023 clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis.
OBJECTIVES
The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis.
METHODS
PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach.
RESULTS
For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively.
CONCLUSIONS
This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Rituximab; Glucocorticoids; Japan; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Remission Induction; Antibodies, Antineutrophil Cytoplasmic; Recurrence
PubMed: 36112482
DOI: 10.1093/mr/roac114 -
Archives of Dermatology Apr 2011To summarize evidence regarding the effectiveness, efficacy, and safety of off-label azathioprine use in dermatology. (Review)
Review
OBJECTIVE
To summarize evidence regarding the effectiveness, efficacy, and safety of off-label azathioprine use in dermatology.
DATA SOURCES
We searched the MEDLINE (1950-2009), EMBASE (1980-2009), and CENTRAL (1996-2009) databases on October 9, 2009. The main search terms were azathioprine and its synonyms. No restrictions were imposed regarding publication date. Only articles in English, French, German, or Dutch were included.
STUDY SELECTION
Randomized controlled trials, cohorts, and case series concerning the use of azathioprine in an off-label dermatologic setting were independently assessed for eligibility by 2 coauthors. The search retrieved 3870 articles, and 148 articles were selected for detailed review.
DATA EXTRACTION
Forty-three articles matching the inclusion and exclusion criteria were reviewed for methodologic quality by 2 reviewers independently, including an evaluation of components associated with biased estimates of treatment effect.
DATA SYNTHESIS
High-quality evidence (level A) was found for a moderate therapeutic effect in severe atopic dermatitis. Evidence of moderate quality (level B) was found for efficacy in parthenium dermatitis (an airborne plant allergen contact dermatitis), bullous pemphigoid, chronic actinic dermatitis, and leprosy type 1 reaction. Furthermore, favorable therapeutic effects existed for erythema multiforme, lichen planus, and pityriasis rubra pilaris, although the quality of evidence was low (level C).
CONCLUSIONS
A strong clinical recommendation was given for azathioprine in atopic dermatitis. Conclusions regarding safety in an off-label setting could not be reached because of scarce and incomplete data (level C evidence). Long-term registries and prospective studies could add to the existing evidence and provide legal support for off-label drug use in dermatology.
Topics: Azathioprine; Dermatologic Agents; Female; Humans; Leprosy; Male; Off-Label Use; Randomized Controlled Trials as Topic; Skin Diseases
PubMed: 21482898
DOI: 10.1001/archdermatol.2011.79 -
BMJ Clinical Evidence May 2009Multiple 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 June 2008 (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 68 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: Administration, Oral; Adrenal Cortex Hormones; Fatigue; Humans; Interferon-beta; Multiple Sclerosis; Muscle Spasticity; Physical Therapy Modalities
PubMed: 21733201
DOI: No ID Found -
Frontiers in Medicine 2022Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved...
INTRODUCTION
Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved patient relief.
OBJECTIVE
To evaluate the effect of AD treatments on pruritus.
METHODS
A systematic literature review and a meta-analysis were conducted to evaluate and compare the effects of treatment used in AD on pruritus. PubMed and Embase databases were searched to find articles published between January 1990 and December 2021. Topical and systemic treatments were studied in patients aged ≥10 years.
RESULTS
Among the 448 articles identified, 56 studies were retained in the systematic review. A total of 15 studies evaluated topical treatments: topical corticosteroids (TCS; 2), calcineurin inhibitors (6), PDE4 inhibitors (3), and Jak inhibitors (4). A total of five studies were included in the meta- analysis. All treatments had a positive effect on pruritus, with a mean overall reduction of 3.32/10, 95% IC [2.32-4.33]. The greatest reduction was observed with halometasone (mean: 4.75), followed by tofacitinib 2% (mean: 4.38). A total of 41 studies evaluated systemic therapies: cyclosporine (6), phototherapy (5), azathioprine (2), dupilumab (9), anti-IL 13 (5), nemolizumab (3), Jak inhibitors (9), mepolizumab (1), and apremilast (1). A total of 17 studies were included in 2 meta-analyses according to the concomitant use or not of TCS. In the meta-analysis without TCS, the overall decrease was 3.07/10, 95% IC [2.58-3.56]. The molecules with the highest efficacy on pruritus were upadacitinib 30 mg (mean: 4.90) and nemolizumab (mean: 4.81).
DISCUSSION
The therapeutic arsenal for AD has increased rapidly, and many molecules are under development. The primary endpoint of clinical trials is most often a score that assesses the severity of AD; however, the assessment of pruritus is also essential. The majority of molecules have a positive effect on pruritus, but the improvement varies between them. Efficacy on pruritus is not always correlated with efficacy on AD lesions; therefore, these two criteria are crucial to evaluate. The limitations of this study were the heterogeneity in the assessment of pruritus, the moment of the assessment, and the concomitant application of TCS or not for studies evaluating systemics. In the future, it would be useful to use standardized criteria for assessing pruritus.
PubMed: 36619624
DOI: 10.3389/fmed.2022.1079323 -
Inflammatory Bowel Diseases Jan 2013Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction... (Review)
Review
BACKGROUND
Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD.
METHODS
A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities.
RESULTS
In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25).
CONCLUSIONS
Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.
Topics: Azathioprine; Congenital Abnormalities; Female; Humans; Immunosuppressive Agents; Infant, Low Birth Weight; Infant, Newborn; Inflammatory Bowel Diseases; Male; Mercaptopurine; Meta-Analysis as Topic; Odds Ratio; Pregnancy; Pregnancy Complications; Premature Birth; Prognosis
PubMed: 22434610
DOI: 10.1002/ibd.22948 -
BMJ Clinical Evidence Nov 2010Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous... (Review)
Review
INTRODUCTION
Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (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 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty.
Topics: Crohn Disease; Genetic Predisposition to Disease; Humans; Inflammation; Life Style; Remission Induction; Smoking Cessation
PubMed: 21406129
DOI: No ID Found -
European Journal of Paediatric... Jan 2019Available data on mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX) for paediatric-onset anti-N-methyl-d-aspartate receptor encephalitis...
BACKGROUND
Available data on mycophenolate mofetil (MMF), azathioprine (AZA) and methotrexate (MTX) for paediatric-onset anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is limited.
METHODS
Systematic literature review on patients treated with MMF/AZA/MTX for paediatric-onset anti-NMDARE, with focus on modes of use, efficacy and safety.
RESULTS
87 patients were included (age at onset median 11 years, range 0.8-18 years; 69% females). 46% had a relapsing course. 52% received MMF, 27% AZA, 15% MTX, and 6% a combination of MMF/AZA/MTX (7 patients received intrathecal MTX). Before MMF/AZA/MTX, 100% patients received steroids, 83% intravenous immunoglobulin and 45% plasma exchange, and 50% received second-line treatments (rituximab/cyclophosphamide). MMF/AZA/MTX were administered >6 months from onset in 51%, and only after relapse in 40%. Worst mRS before MMF/AZA/MTX was median 4.5 (range 3-5). At last follow-up (median 2 years, range 0.2-8.6), median mRS was 1 (range 0-6). Median annualised relapse rate was 0.4 (range 0-6.7) pre-MMF/AZA/MTX (excluding first events), and 0 on MMF/AZA/MTX (mean 0.03, range 0-0.8). 7% patients relapsed on MMF/AZA/MTX. These relapsing patients had low rate of second-line treatments before MMF/AZA/MTX (25%), long median time between onset and MMF/AZA/MTX usage (18 months), and frequently they were started on MMF/AZA/MTX only after relapse (75%). Relapse rate was lower among patients who received first immune therapy ≤30 days (25%) than later (64%), who received second-line treatments at first event (14%) rather than not (64%), who were started on MMF/AZA/MTX after the first (12%) rather than subsequent events (17%), and who were started on MMF/AZA/MTX ≤3 months from onset (33%) rather than later (53%). Adverse reactions to MMF/AZA/MTX occurred in 2 cases (cytomegalovirus colitis and respiratory infection), of grade 3 Common Terminology Criteria for Adverse Events v4.0.
DISCUSSION
Our literature review disclosed heterogeneity in the use of MMF/AZA/MTX in paediatric-onset anti-NMDARE. MMF/AZA/MTX usage is mostly restricted to retrospective cohort descriptions. These agents may reduce risk of relapse, and have a reasonable safety profile, however data on larger cohorts are required to definitively determine effect.
Topics: Adolescent; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Azathioprine; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents; Infant; Male; Methotrexate; Mycophenolic Acid
PubMed: 30318435
DOI: 10.1016/j.ejpn.2018.09.008 -
Rheumatology (Oxford, England) May 2014The objective of this study was to summarize the comparative efficacy and safety of MMF and AZA as maintenance therapy for LN. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
The objective of this study was to summarize the comparative efficacy and safety of MMF and AZA as maintenance therapy for LN.
METHODS
Systematic review and meta-analysis of randomized clinical trials of MMF and AZA as maintenance therapy for LN were performed based on a sensitive search. Meta-regression was used to explore causes of heterogeneity. Safety was explored using crude and combined incidence rate ratios (IRRs) of the more frequent adverse events (AEs).
RESULTS
The search produced 7341 hits. Four randomized clinical trials and one long-term study were selected for detailed analysis. No significant differences between MMF and AZA were found in sustained remission, relapse, renal failure, creatinine increase or death. However, there was high heterogeneity in the design of studies, drug doses and treatment in the previous induction phase. Significant lower rates of discontinuation due to AEs occurred in the MMF group, with a relative risk (RR) of 0.60 (95% CI 0.41, 0.88) but significant risk of publication bias (Egger test, P = 0.012). Gastrointestinal manifestations were more common [combined IRR 1.68 (95% CI 1.06, 2.68)] and leucopoenia less frequent in the MMF group [combined IRR 0.14 (95% CI 0.05, 0.42)].
CONCLUSION
The available data does not support the superiority of MMF or AZA as maintenance therapy for LN. Nevertheless, the high heterogeneity of studies included in the analysis makes this contention questionable.
Topics: Adult; Azathioprine; Disease Management; Humans; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24369416
DOI: 10.1093/rheumatology/ket429