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Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease...
BACKGROUND AND PURPOSE
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease of the central nervous system. The clinical features and prognosis of MOGAD adult cerebral cortical encephalitis (adult CCE) have not been fully elucidated. This study aims to further characterize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of CCE with anti-MOG antibody.
METHODS
We present two adult cases of CCE with anti-MOG antibody and summarize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of this phenotype as per a completed systematic review of the literature.
RESULTS
We found a total of 39 cases of MOGAD adult CCE (36% females; average age of onset of 29 years). Among them, 85% had seizure, 82% had headache, 64% had cortical symptoms, 64% had fever, 54% had changes of consciousness, and 38% had ocular symptoms. All cases demonstrated cerebral cortical T2 fluid-attenuated inversion recovery (FLAIR) lesions on MRI. Of the 25 patients (with seizure or not) who had EEG reports, 76% of patients showed abnormal EEG. Cerebrospinal fluid (CSF) white blood cell count of 90% of patients and CSF total protein of 67% of patients were elevated. In 16 patients with available CSF cytology data, 11 (69%) had abnormal cytology findings with monocytic predominance. In the 15 cases for which MOG antibody IgG was tested in both serum and CSF, 14 (93%) demonstrated a higher positive MOG IgG titer in serum than CSF. The majority of patients were treated with immunosuppressive therapy (97% corticosteroids, 15% mycophenolate mofetil, 13% IVIg, 5% azathioprine, and 5% other). The majority of patients had a favorable prognosis after treatment, as exemplified by improved clinical symptoms and imaging. Two patients relapsed.
CONCLUSIONS
The clinical presentation and prognosis of adult CCE remain less understood in comparison to more common MOGAD phenotypes. It is important to consider MOGAD as an underlying etiology for adult CCE, as early detection and immunotherapy may improve outcomes.
Topics: Female; Male; Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Encephalitis; Seizures; Immunoglobulin G; Oligodendroglia
PubMed: 37520572
DOI: 10.3389/fimmu.2023.1203615 -
The Cochrane Database of Systematic... Jan 2020Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions involve the use of steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This 2019 publication is an update of a review first published in 2008 and updated in 2015.
OBJECTIVES
To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 21 November 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
Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes.
MAIN RESULTS
Forty studies (3764 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large international study groups. Induction therapy: Plasma exchange as adjunctive therapy may reduce the need for dialysis at three (2 studies: RR 0.43, 95% CI 0.23 to 0.78; I = 0%) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72; I = 0%) (low certainty evidence). Plasma exchange may make little or no difference to death, serum creatinine (SCr), sustained remission or to serious or the total number of adverse events. Plasma exchange may increase the number of serious infections (5 studies: RR 1.26, 95% CI 1.03 to 1.54; I = 0%; low certainty evidence). Remission rates for pulse versus continuous cyclophosphamide (CPA) were equivalent but pulse treatment may increase the risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87; I = 0%) (low certainty evidence) compared with continuous cyclophosphamide. Pulse CPA may make little or no difference to death at final follow-up, or SCr at any time point. More patients required dialysis in the pulse CPA group. Leukopenia was less common with pulse treatment; however, nausea was more common. Rituximab compared to CPA probably makes little or no difference to death, remission, relapse, severe adverse events, serious infections, or severe adverse events. Kidney function and dialysis were not reported. A single study reported no difference in the number of deaths, need for dialysis, or adverse events between mycophenolate mofetil (MMF) and CPA. Remission was reported to improve with MMF however more patients relapsed. A lower dose of steroids was probably as effective as high dose and may be safer, causing fewer infections; kidney function and relapse were not reported. There was little of no difference in death or remission between six and 12 pulses of CPA. There is low certainty evidence that there were less relapses with 12 pulses (2 studies: RR 1.57, 95% CI 0.96 to 2.56; I = 0%), but more infections (2 studies: RR 0.79, 95% CI 0.36 to 1.72; I = 45%). One study reported severe adverse events were less in patients receiving six compared to 12 pulses of CPA. Kidney function and dialysis were not reported. There is limited evidence from single studies about the effectiveness of intravenous immunoglobulin, avacopan, methotrexate, immunoadsorption, lymphocytapheresis, or etanercept. Maintenance therapy: Azathioprine (AZA) has equivalent efficacy as a maintenance agent to CPA with fewer episodes of leucopenia. MMF resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction and maintenance agent. Oral co-trimoxazole did not reduce relapses in granulomatosis with polyangiitis. There were fewer relapses but more serious adverse events with leflunomide compared to methotrexate. There is limited evidence from single studies about the effectiveness of methotrexate versus CPA or AZA, cyclosporin versus CPA, extended versus standard AZA, and belimumab.
AUTHORS' CONCLUSIONS
Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst CPA is standard induction treatment, rituximab and MMF were also effective. AZA, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
Topics: Acute Kidney Injury; Adult; Azathioprine; Cyclophosphamide; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Failure, Chronic; Plasma Exchange; Randomized Controlled Trials as Topic; Vasculitis
PubMed: 31927782
DOI: 10.1002/14651858.CD003232.pub4 -
BioMed Research International 2018Graves' ophthalmopathy (GO) is a complicated autoimmune disease. Various therapies have been used to manage GO; however the optimum therapy is not clear. Glucocorticoids... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Graves' ophthalmopathy (GO) is a complicated autoimmune disease. Various therapies have been used to manage GO; however the optimum therapy is not clear. Glucocorticoids (GCs) therapy is the mainstay of treatment especially for active moderate to severe patients, which needs evidence-based support.
METHOD
We searched all the randomized controlled trials (RCTs) involving corticosteroid treatment for patients diagnosed with GO from EMBASE, Medline, and the Cochrane library and then conducted a system review and meta-analysis. The electronic search covered the period from April 1966 to March 2018.
RESULT
Twenty-nine trials were included. GCs were proved to be beneficial for GO patients [response rate, risk ratio (RR) = 1.72, 95% confidence interval (CI): 1.28~2.31, P=0.0003], and intravenous corticosteroids worked significantly better than oral corticosteroids as ever reported. When compared with the single treatment of GCs, the combination of radiotherapy and GCs showed similar effects on response rate (RR=1.25, 95%CI: 0.91~1.73). A study proved the advantage of mycophenolate mofetil over GCs in three outcomes (response rate, RR=0.74, 95%CI: 0.63~0.88). Additional treatments such as technetium-99 methylene diphosphate (Tc-MDP) or cyclosporine enhanced the effect of GCs on proptosis reduction, respectively (P<0.00001 and P=0.02).
CONCLUSION
Our meta-analysis confirmed the effects of GCs in the management of GO and intravenous GCs are proved to be better than oral GCs as ever reported. Combination of radiotherapy and GCs did not enhance the effects of GCs. However, if proptosis is the main issue, combination of Tc-MDP or cyclosporine with GCs may be taken into consideration. The reported advantages of mycophenolate mofetil over GCs are noteworthy and need more RCTs to confirm.
Topics: Adrenal Cortex Hormones; Cyclosporine; Graves Ophthalmopathy; Humans; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 30596092
DOI: 10.1155/2018/4845894 -
Vaccines Jun 2023The pediatric population is at a lower risk of severe SARS-CoV-2 infection compared to adults. Nevertheless, immunosuppression in pediatric and adolescent kidney... (Review)
Review
The pediatric population is at a lower risk of severe SARS-CoV-2 infection compared to adults. Nevertheless, immunosuppression in pediatric and adolescent kidney transplant recipients (KTRs) increases their hazard compared to the general population. This systematic review evaluates the efficacy of SARS-CoV-2 vaccines and determines the risk factors of no seroconversion in this population. PubMed-MEDLINE databases were searched for cohort studies. A meta-analysis was performed using fixed and random effect models. In total, seven studies including 254 patients were further analyzed. The random effect model demonstrated a 63% seroconversion rate (95% CI 0.5, 0.76) following a two-dose schedule, which increased to 85% (95% CI 0.76, 0.93) after the third dose administration. Seropositivity was lower in patients under mycophenolate mofetil compared to azathioprine (OR 0.09, 95% CI 0.02, 0.43). Rituximab administration decreased the seroconversion rate (OR 0.12, 95% CI 0.03, 0.43). The glomerular filtration rate (GFR) was 9.25 mL/min/1.73 m lower (95% CI 16.37, 2.13) in patients with no seroconversion. The seroconversion rate was lower in vaccinated compared to infected patients (OR 0.13, 95% CI 0.02, 0.72). In conclusion, vaccination against SARS-CoV-2 in pediatric and adolescent KTRs elicits a humoral response, and a third dose is advised. Previous rituximab administration, antimetabolite therapy with mycophenolate mofetil and lower GFR reduce the likelihood for seroconversion.
PubMed: 37376469
DOI: 10.3390/vaccines11061080 -
World Journal of Gastroenterology Jun 2019Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease with a high risk of progression to liver cirrhosis. The initial treatment for AIH usually...
BACKGROUND
Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease with a high risk of progression to liver cirrhosis. The initial treatment for AIH usually includes a steroid, with or without azathioprine. AIH can present at any age; however, the most effective and safe induction treatment for AIH in the elderly remains unclear.
AIM
To systematically review available data on both effectiveness and safety of AIH treatments in elderly subjects.
METHODS
To identify studies on AIH induction treatment in elderly patients (≥ 60 years of age), an electronic research was performed (PubMed, EMBASE and Cochrane Library databases) until February 2019. Eligible studies were selected through screening of titles and abstracts, followed by full-text critical evaluation. After risk of bias assessment, data on study designs, interventions, and outcomes were extracted and reviewed.
RESULTS
Among the 1736 retrieved papers, 15 studies were selected. Out of them, eight studies were excluded because of a critical risk of bias. The remaining seven studies included 789 patients and out of them 239 subjects were elders. First-line treatment was a steroid either alone or in combination with azathioprine in most patients (87.6%) and only one study investigated the effect of combined steroid and mycophenolate mofetil therapy. Standard therapy was effective in inducing remission in the elderly. Moreover, treatment failure and relapses occurred less often in the elderly compared to younger people.
CONCLUSION
Treatment of AIH is challenging in elderly patients. This systematic review confirms the efficacy and safety of standard induction treatment for AIH in the elderly. Available evidence is insufficient to draw any conclusion on the effect of novel AIH treatments in elderly subjects.
Topics: Age Factors; Aged; Azathioprine; Disease Progression; Drug Therapy, Combination; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Remission Induction; Treatment Outcome
PubMed: 31236003
DOI: 10.3748/wjg.v25.i22.2809 -
Drugs in R&D Dec 2018Globally, enteric-coated mycophenolate sodium (EC-MPS) is replacing mycophenolate mofetil (MMF) in maintenance immunosuppressant regimens. The predominant reason for...
BACKGROUND
Globally, enteric-coated mycophenolate sodium (EC-MPS) is replacing mycophenolate mofetil (MMF) in maintenance immunosuppressant regimens. The predominant reason for conversion is the purported improvement in gastrointestinal (GI) quality of life. This paper considers the level of bias associated with studies comparing EC-MPS and MMF for GI-related improvement and provides insight into whether conversion is supported by evidence.
METHODS
Using a pre-determined protocol, a literature search was conducted. Full-text review, data extraction and risk of bias analysis was conducted by two independent authors using the Cochrane domain-based evaluation of risk of bias. The review was reported according to the preferred reporting items for systematic reviews and meta-analyses.
RESULTS
Twenty-nine studies were included in risk of bias analysis. Of these, only three were deemed a low risk of bias. Across these three studies, there were no statistically significant differences in the proportion of GI-related adverse events nor was there a significant difference in the GI-related quality of life between EC-MPS- and MMF-treated patients in these data.
CONCLUSION
There was a high risk of bias across the 29 studies investigating conversion from MMF to EC-MPS for potential improvement in GI-related quality of life. The consolidated results of the three studies with low risk of bias suggest no evidence to convert patients stabilised on MMF. If a patient experiences GI-related adverse events whilst taking MMF, other methods should be explored before conversion to EC-MPS.
Topics: Gastrointestinal Tract; Humans; Immunosuppressive Agents; Mycophenolic Acid; Quality of Life; Tablets, Enteric-Coated
PubMed: 30426342
DOI: 10.1007/s40268-018-0254-8 -
Autoimmunity Reviews Jan 2022The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates.
METHODS
Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes.
RESULTS
Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I = 90%) as compared to a single dose (69.3, 52.4-82.3, I = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy.
CONCLUSION
Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.
Topics: COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Tumor Necrosis Factor Inhibitors; Vaccination
PubMed: 34474172
DOI: 10.1016/j.autrev.2021.102927 -
Clinical Medicine Insights.... 2022Heart transplant (HTX) recipients are at a significantly higher risk of adverse clinical outcomes, due to chronic immunosuppression and co-existence of other chronic... (Review)
Review
BACKGROUND
Heart transplant (HTX) recipients are at a significantly higher risk of adverse clinical outcomes, due to chronic immunosuppression and co-existence of other chronic conditions, when contracting the SARS-CoV-2 infection. Although vaccination against SARS-CoV-2 is currently the most promising measure for the prevention of severe Coronavirus Disease 2019 (COVID-19) among solid organ transplant recipients, the extent of immune response and its protective efficacy among patients receiving HTX has not been sufficiently studied.
METHODS
We performed a systematic review of the literature by inquiring PubMed/Medline to identify original studies among HTX recipients, who had received at least one dose of the SARS-CoV-2 vaccine. Data on the measured humoral or cellular immune response was collected from all the eligible studies. Factors associated with a poor immune response were further investigated within these studies.
RESULTS
A total of 12 studies comprising 563 HTX recipients were included. The average age of the study participants was 60.8 years. Sixty four percent of the study population were male. Ninety percent of the patients had received an mRNA vaccine (Pfizer/ BNT162b2 or Moderna/mRNA-1273). A positive immune response to SARS-CoV-2 vaccine was variably reported in 0% to 100% of the patients. Older age (> 65 years), vaccine dose (first, second, or third), time since HTX to the first dose of the vaccine, the time interval between the latest dose of the vaccine and measurement of the immune response, and the type of immunosuppressive regimen were all indicated as potential determinants of a robust immune response to the SARS-CoV-2 vaccination.
CONCLUSION
HTX recipients demonstrate a weaker immune response to the vaccination against SARS-CoV-2 compared to the general population. Older age, anti-metabolite agents such as mycophenolate mofetil, and vaccination during the first year following the HTX have been indicated as potential determinants of a poor immune response.
PubMed: 35693423
DOI: 10.1177/11795484221105327 -
Frontiers in Immunology 2022Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear.
AIM
To identify the efficacy and tolerability of different treatments for MOG-AD.
METHODS
Systematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI).
RESULTS
Twelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=-0.85, 95% CrI: -1.7 to -0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies.
CONCLUSIONS
Whilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives.
Topics: Azathioprine; Bayes Theorem; Demyelinating Autoimmune Diseases, CNS; Humans; Immunoglobulins, Intravenous; Mycophenolic Acid; Network Meta-Analysis; Recurrence; Rituximab
PubMed: 35958613
DOI: 10.3389/fimmu.2022.953993 -
Seminars in Arthritis and Rheumatism Aug 2017We aimed to summarize the evidence examining factors that predict differential response to mycophenolate mofetil (MMF) in systemic lupus erythematosus (SLE).
OBJECTIVES
We aimed to summarize the evidence examining factors that predict differential response to mycophenolate mofetil (MMF) in systemic lupus erythematosus (SLE).
METHODS
Systematic searches of randomized clinical trials (RCT) to identify predictors of the effects of MMF (moderators), and cohort studies to explore prognostic factors associated with MMF outcomes (response, relapse, or adverse events) were performed. Two reviewers independently assessed the methodological quality of RCTs using the Cochrane Collaboration risk of bias tool and cohort studies using the QUality In Prognosis Studies tool. The quality of subgroup analysis, providing evidence for moderation, was evaluated. The Grading of Recommendations Assessment, Development, and Evaluation working group approach summarized the quality of evidence (QoE), considering the risk of bias, imprecision, inconsistency, indirectness, and publication bias.
RESULTS
From 26 studies (13 from 7 RCTs and 13 cohort studies) we found low QoE evidence for Black/Hispanic race/ethnicity predicting better renal responses to MMF in lupus nephritis (LN) from one RCT. There was low QoE evidence from cohort studies that a higher baseline creatinine and membranous features on renal biopsy were associated with poorer responses in LN. There was very low QoE for other moderators or prognostic factors associated with MMF treatment outcomes. QoE from RCTs was affected by exploratory or insufficient evidence from subgroup analysis and in both study types high risk of bias, indirectness and imprecision also affected QoE.
CONCLUSIONS
In SLE, evidence for predictors of response to MMF is limited and none can be recommended for use in routine clinical practice. Specific studies of predictors measured at baseline and during treatment are needed with a priori hypotheses based on preliminary evidence to date and with sufficient power to determine which factors can be employed in clinical decision making.
Topics: Humans; Immunosuppressive Agents; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid; Patient-Centered Care; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 28325471
DOI: 10.1016/j.semarthrit.2017.01.009