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Frontiers in Immunology 2022Comèl-Netherton syndrome (NS) is a rare disease caused by pathogenic variants in the gene, leading to severe skin barrier impairment and proinflammatory upregulation....
BACKGROUND
Comèl-Netherton syndrome (NS) is a rare disease caused by pathogenic variants in the gene, leading to severe skin barrier impairment and proinflammatory upregulation. Given the severity of the disease, treatment of NS is challenging. Current treatment regimens are mainly topical and supportive. Although novel systemic treatment options for NS have been suggested in recent literature, little is known about their outcomes.
OBJECTIVE
to provide an overview of systemic treatment options and their outcomes in adults and children with NS.
METHODS
Embase, MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to July 22, 2021. Empirical studies published in English language mentioning systemic treatment in NS were enrolled. Studies that did not define a treatment period or report at least one outcome were excluded. Methodological quality was evaluated by the Joanna Briggs Institute critical appraisal checklist for case reports or case series. Overall quality of evidence of the primary outcome, skin, was assessed by the GRADE approach.
RESULTS
36 case series and case reports were included. The effects of 15 systemic therapies were described in 48 patients, of which 27 were children. Therapies included retinoids, prednisolone, cyclosporine, immunoglobulins, and biologicals. In retinoids both worsening (4/15 cases) and improvement (6/15 cases) of the skin was observed. Use of prednisolone and cyclosporine was only reported in one patient. Immunoglobulins (13/15 cases) and biologicals (18/21 cases) showed improvement of the skin. Certainty of evidence was rated as very low.
CONCLUSION
NS is a rare disease, which is reflected in the scarce literature on systemic treatment outcomes in children and adults with NS. Studies showed large heterogeneity in outcome measures. Adverse events were scarcely reported. Long-term outcomes were reported in a minority of cases. Nonetheless, a general beneficial effect of systemic treatment was found. Immunoglobulins and biologicals showed the most promising results and should be further explored. Future research should focus on determining a core outcome set and measurement instruments for NS to improve quality of research.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=217933, PROSPERO (ID: 217933).
Topics: Adult; Child; Cyclosporine; Humans; Netherton Syndrome; Prednisolone; Rare Diseases; Retinoids
PubMed: 35464459
DOI: 10.3389/fimmu.2022.864449 -
Acta Ophthalmologica Aug 2022To evaluate the efficacy of preventive treatment against allograft rejection after endothelial keratoplasty (EK), we conducted a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the efficacy of preventive treatment against allograft rejection after endothelial keratoplasty (EK), we conducted a systematic review and meta-analysis.
METHOD
PubMed, Cochrane Library, Embase and ScienceDirect databases were searched until May 2021. We computed a random-effect meta-analysis on graft rejection rate stratified by the intervention (i.e. Descemet membrane EK (DMEK) and Descemet stripping (Automated) EK (DS(A)EK) or ultrathin (UT)-DSAEK), and postoperative treatment. Meta-regressions were performed to compare intervention, treatment and influence of putative confusion factors.
RESULTS
We included 49 studies and 12 893 EK (6867 DMEK and 6026 DS(A)EK/UT-DSAEK). Topical steroids were merged in two efficacy regimens: standard steroids (prednisolone acetate 1% or dexamethasone 0.1%) and soft steroids (fluorometholone 0.1% or loteprednol etabonate 0.5%). Globally, DMEK had a lower graft rejection rate than DS(A)EK/UT-DSAEK (coefficient - 3.3, 95 CI, -4.60 to -1.90; p < 0.001). No significant differences were observed between standard and soft steroids to prevent graft rejection after DMEK. After EK, the rate of ocular hypertension was 20% (95 CI, 14 to 26%) with the use of standard steroids and 7% (5 to 9%) with soft steroids. Comparisons of treatments were not feasible in DS(A)EK/UT-DSAEK due to a lack of studies.
CONCLUSIONS
Descemet membrane endothelial keratoplasty (DMEK) has less risk of graft rejection compared with DS(A)EK/UT-DSAEK. Furthermore, soft steroids seemed to be a valuable alternative to standard steroids to prevent graft rejection after DMEK, involving a safe profile against ocular hypertension. Further studies are needed to compare other drugs in the prevention of graft rejection after EK.
Topics: Allografts; Corneal Diseases; Descemet Membrane; Descemet Stripping Endothelial Keratoplasty; Endothelium, Corneal; Fuchs' Endothelial Dystrophy; Glaucoma; Humans; Ocular Hypertension; Retrospective Studies; Visual Acuity
PubMed: 35411680
DOI: 10.1111/aos.15154 -
Journal of Pharmacy & Pharmaceutical... 2022Till date, only systemic corticosteroids have demonstrated definite mortality benefit in management of COVID 19 in various studies. Still certain questions regarding the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Till date, only systemic corticosteroids have demonstrated definite mortality benefit in management of COVID 19 in various studies. Still certain questions regarding the appropriate dose, duration and timing of corticosteroids remain unanswered. For this reason, the study was planned to determine the efficacy and safety of the pulse dose methyl prednisolone in management of COVID 19 from the publicly available evidence.
METHODS
PubMed, the Cochrane library, ClinicalTrials.gov and medRxiv were searched for articles reporting the use of pulse dose methyl prednisolone in COVID 19 from inception till 31st May, 2021. Odds ratios (ORs) were calculated for estimation of pooled effect by using random effect model and heterogeneity was checked by using I2 statistics.
RESULTS
Twelve studies (11 observational and 1 RCT) were included in the systematic review. A total of 3110 patients from 9 studies were included in the meta-analysis. Though the use of pulse dose methyl prednisolone demonstrated statistically significant mortality benefit in comparison to usual care (OR=0.71, 95% CI: 0.51 to 0.97, [P=0.03]), (I2= 21%) with calculated Number needed to treat (NNT) of 23.5, there was no statistically significant difference between the use of pulse dose and low dose corticosteroid (OR=0.66, 95% CI: 0.44 to 1.01, [(P=0.05]), (I2= 25%) and the NNT is 23.5. Incidence of adverse events were similar across all the groups. The grade of evidence for primary outcome was of moderate certainty.
CONCLUSION
This meta-analysis concurs with the previous reports regarding the use of corticosteroid in COVID 19 in comparison to usual care. However, for both the primary and secondary outcome, the study did not find any statistically significant difference between the use of pulse dose methyl prednisolone and low dose corticosteroid to treat COVID 19 patients.
Topics: Adrenal Cortex Hormones; Humans; Methylprednisolone; COVID-19 Drug Treatment
PubMed: 35364003
DOI: 10.18433/jpps32430 -
Medicine Feb 2022Several epidemiological studies have shown that silica exposure triggers the onset of systemic lupus erythematosus (SLE); however, the clinical characteristics of...
INTRODUCTION
Several epidemiological studies have shown that silica exposure triggers the onset of systemic lupus erythematosus (SLE); however, the clinical characteristics of silica-associated SLE have not been well studied.
PATIENT CONCERNS
A 67-year-old man with silicosis visited a primary hospital because of a fever and cough. His respiratory condition worsened, regardless of antibiotic medication, and he was referred to our hospital.
DIAGNOSIS
The patient showed leukopenia, lymphopenia, serum creatinine elevation with proteinuria and hematuria, decreased serum C3 level, and was positive for anti-double stranded DNA antibody, anti-nuclear antibody, and direct Coombs test. He was diagnosed with SLE. Renal biopsy was performed, and the patient was diagnosed with lupus nephritis (class IV-G(A/C) + V defined by the International Society of Nephrology/Renal Pathology Society classification). Computed tomography revealed acute interstitial pneumonitis, bronchoalveolar lavage fluid showed elevation of the lymphocyte fraction, and he was diagnosed with lupus pneumonitis.
INTERVENTIONS
Prednisolone (50 mg/day) with intravenous cyclophosphamide (500 mg/body) were initiated.
OUTCOMES
The patient showed a favorable response to these therapies. He was discharged from our hospital and received outpatient care with prednisolone slowly tapered off. He had cytomegalovirus and herpes zoster virus infections during treatment, which healed with antiviral therapy.
REVIEW
We searched for the literature on sSLE, and selected 11 case reports and 2 population-based studies. The prevalence of SLE manifestations in sSLE patients were comparative to that of general SLE, particularly that of elderly-onset SLE. Our renal biopsy report and previous reports indicate that lupus nephritis of sSLE patients show as various histological patterns as those of general SLE patients. Among the twenty sSLE patients reported in the case articles, three patients developed lupus pneumonitis and two of them died of it. Moreover, two patients died of bacterial pneumonia, one developed aspergillus abscesses, one got pulmonary tuberculosis, and one developed lung cancer.
CONCLUSION
Close attention is needed, particularly for respiratory system events and infectious diseases, when treating patients with silica-associated SLE using immunosuppressive therapies.
Topics: Aged; Humans; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Pneumonia, Bacterial; Silicon Dioxide
PubMed: 35363197
DOI: 10.1097/MD.0000000000028872 -
Steroids Jul 2022The roles of methylprednisolone in treatment of patients with COVID-19 remain unclear. The aim of this study was to evaluate the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
The roles of methylprednisolone in treatment of patients with COVID-19 remain unclear. The aim of this study was to evaluate the efficacy and safety of methylprednisolone in treatment of COVID-19 patients. PubMed, Cochrane and Web of Science were searched for studies comparing methylprednisolone and no glucocorticoids treatment in patients with COVID-19. Statistical pooling was reported as risk ratio (RR) or mean difference (MD) with corresponding 95 % confidence interval (CI). Thirty-three studies were eligible, including 5 randomized trials and 28 observational studies. Meta-analysis showed that compared with no glucocorticoids, methylprednisolone in treatment of COVID-19 patients was associated with reduced short-term mortality (RR 0.73; 95% CI 0.60-0.89), less need for ICU admission (RR 0.77; 95% CI 0.66-0.91) and mechanical ventilation (RR 0.69; 95% CI 0.57-0.84), increased 28-day ventilator-free days (MD 2.81; 95% CI 2.64-2.97), without increasing risk of secondary infections (RR 1.04; 95% CI 0.82-1.32), but could prolong duration of viral shedding (MD 1.03; 95% CI 0.25-1.82). Subgroup analyses revealed that low-dose (≤2mg/kg/day) methylprednisolone treatment for ≤ 7 days in severe COVID-19 patients was associated with relatively better clinical outcomes, without increasing duration of viral shedding. Compared with no glucocorticoids, methylprednisolone treatment in COVID-19 patients is associated with reduced short-term mortality and better clinical outcomes, without increasing secondary infections, but could slightly prolong duration of viral shedding. Patients with severe COVID-19 are more likely to benefit from short-term low-dose methylprednisolone treatment (1-2 mg/kg/day for ≤ 7 days).
Topics: Coinfection; Glucocorticoids; Humans; Methylprednisolone; Respiration, Artificial; COVID-19 Drug Treatment
PubMed: 35346661
DOI: 10.1016/j.steroids.2022.109022 -
Frontiers in Immunology 2022A close association between psoriasis and anti-p200 pemphigoid has been demonstrated by numerous studies. However, the clinical characteristics of patients suffering...
BACKGROUND
A close association between psoriasis and anti-p200 pemphigoid has been demonstrated by numerous studies. However, the clinical characteristics of patients suffering from these two entities have not yet been well-elucidated.
OBJECTIVE
This study aimed to review the case reports and case series, summarizing clinical features and therapeutic strategies in patients suffering from anti-p200 pemphigoid and psoriasis.
METHODS
A systematic review was conducted by searching PubMed, EMBASE, and Web of Science databases for studies published in English involving patients with psoriasis and anti-p200 pemphigoid on 6 September 2021. All case reports and case series reporting patients diagnosed with anti-p200 pemphigoid and psoriasis were included in this systematic review.
RESULTS
A total of 21 eligible studies comprising 26 anti-p200 pemphigoid patients with preceding psoriasis were included in the qualitative synthesis. The average age at blisters eruption was 62.5 years, and the mean duration between the two entities was 15.6 years. Twenty-four percent of patients developed bullous lesions during UV therapy. Clinical manifestation of bullae and/or vesicles was recorded in all patients, and the trunk (94.7%) was most frequently involved, with only 15.8% reporting mucosal involvement. Epitope spreading was detected by immunoblotting in 33.3% of patients. All the patients reached completed remission during the course of disease, with 36.8% experiencing at least one relapse. Monotherapy of prednisolone was the leading therapeutic approach (n=6, 31.6%) required for disease control, but 5 (83.3%) of them suffered from blister recurrence after tapering or ceasing corticosteroid.
CONCLUSION
Most of the clinical aspects of patients with anti-p200 pemphigoid and psoriasis were similar to what was demonstrated in previous articles on anti-p200 pemphigoid. Nevertheless, compared with other anti-p200 pemphigoid cases without psoriasis, a clinical manifestation pattern with more frequent involvement of the trunk and less mucosal involvement was illustrated in those with psoriasis. Generally, monotherapy is sufficient for a complete remission for such patients. However, one or more relapses have been recorded in a considerable portion of patients, especially those prescribed with prednisolone. It reminded us to be more cautious during a tapering of medication.
Topics: Autoantibodies; Blister; Humans; Laminin; Middle Aged; Pemphigoid, Bullous; Prednisolone; Psoriasis
PubMed: 35317170
DOI: 10.3389/fimmu.2022.839094 -
The Cochrane Database of Systematic... Mar 2022Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by medications. In addition to tertiary-level supportive care, various systemic therapies have been used including glucocorticoids, intravenous immunoglobulins (IVIGs), cyclosporin, N-acetylcysteine, thalidomide, infliximab, etanercept, and plasmapheresis. There is an unmet need to understand the efficacy of these interventions.
OBJECTIVES
To assess the effects of systemic therapies (medicines delivered orally, intramuscularly, or intravenously) for the treatment of SJS, TEN, and SJS/TEN overlap syndrome.
SEARCH METHODS
We searched the following databases up to March 2021: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five clinical trial registers, the reference lists of all included studies and of key review articles, and a number of drug manufacturer websites. We searched for errata or retractions of included studies.
SELECTION CRITERIA
We included only randomised controlled trials (RCTs) and prospective observational comparative studies of participants of any age with a clinical diagnosis of SJS, TEN, or SJS/TEN overlap syndrome. We included all systemic therapies studied to date and permitted comparisons between each therapy, as well as between therapy and placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as specified by Cochrane. Our primary outcomes were SJS/TEN-specific mortality and adverse effects leading to discontinuation of SJS/TEN therapy. Secondary outcomes included time to complete re-epithelialisation, intensive care unit length of stay, total hospital length of stay, illness sequelae, and other adverse effects attributed to systemic therapy. We rated the certainty of the evidence for each outcome using GRADE.
MAIN RESULTS
We included nine studies with a total of 308 participants (131 males and 155 females) from seven countries. We included two studies in the quantitative meta-analysis. We included three RCTs and six prospective, controlled observational studies. Sample sizes ranged from 10 to 91. Most studies did not report study duration or time to follow-up. Two studies reported a mean SCORe of Toxic Epidermal Necrosis (SCORTEN) of 3 and 1.9. Seven studies did not report SCORTEN, although four of these studies reported average or ranges of body surface area (BSA) (means ranging from 44% to 51%). Two studies were set in burns units, two in dermatology wards, one in an intensive care unit, one in a paediatric ward, and three in unspecified inpatient units. Seven studies reported a mean age, which ranged from 29 to 56 years. Two studies included paediatric participants (23 children). We assessed the results from one of three RCTs as low risk of bias in all domains, one as high, and one as some concerns. We judged the results from all six prospective observational comparative studies to be at a high risk of bias. We downgraded the certainty of the evidence because of serious risk of bias concerns and for imprecision due to small numbers of participants. The interventions assessed included systemic corticosteroids, tumour necrosis factor-alpha (TNF-alpha) inhibitors, cyclosporin, thalidomide, N-acetylcysteine, IVIG, and supportive care. No data were available for the main comparisons of interest as specified in the review protocol: etanercept versus cyclosporin, etanercept versus IVIG, IVIG versus supportive care, IVIG versus cyclosporin, and cyclosporin versus corticosteroids. Corticosteroids versus no corticosteroids It is uncertain if there is any difference between corticosteroids (methylprednisolone 4 mg/kg/day for two more days after fever had subsided and no new lesions had developed) and no corticosteroids on disease-specific mortality (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.72 to 9.03; 2 studies; 56 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. IVIG versus no IVIG It is uncertain if there is any difference between IVIG (0.2 to 0.5 g/kg cumulative dose over three days) and no IVIG in risk of disease-specific mortality (RR 0.33, 95% CI 0.04 to 2.91); time to complete re-epithelialisation (mean difference (MD) -2.93 days, 95% CI -4.4 to -1.46); or length of hospital stay (MD -2.00 days, 95% CI -5.81 to 1.81). All results in this comparison were based on one study with 36 participants, and very low-certainty evidence. Adverse effects leading to discontinuation of therapy were not reported. Etanercept (TNF-alpha inhibitor) versus corticosteroids Etanercept (25 mg (50 mg if weight > 65 kg) twice weekly "until skin lesions healed") may reduce disease-specific mortality compared to corticosteroids (intravenous prednisolone 1 to 1.5 mg/kg/day "until skin lesions healed") (RR 0.51, 95% CI 0.16 to 1.63; 1 study; 91 participants; low-certainty evidence); however, the CIs were consistent with possible benefit and possible harm. Serious adverse events, such as sepsis and respiratory failure, were reported in 5 of 48 participants with etanercept and 9 of 43 participants with corticosteroids, but it was not clear if they led to discontinuation of therapy. Time to complete re-epithelialisation and length of hospital stay were not reported. Cyclosporin versus IVIG It is uncertain if there is any difference between cyclosporin (3 mg/kg/day or intravenous 1 mg/kg/day until complete re-epithelialisation, then tapered off (10 mg/day reduction every 48 hours)) and IVIG (continuous infusion 0.75 g/kg/day for 4 days (total dose 3 g/kg) in participants with normal renal function) in risk of disease-specific mortality (RR 0.13, 95% CI 0.02 to 0.98, 1 study; 22 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. No studies measured intensive care unit length of stay.
AUTHORS' CONCLUSIONS
When compared to corticosteroids, etanercept may result in mortality reduction. For the following comparisons, the certainty of the evidence for disease-specific mortality is very low: corticosteroids versus no corticosteroids, IVIG versus no IVIG and cyclosporin versus IVIG. There is a need for more multicentric studies, focused on the most important clinical comparisons, to provide reliable answers about the best treatments for SJS/TEN.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Adult; Autoimmune Diseases; Child; Cyclosporine; Etanercept; Female; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Observational Studies as Topic; Stevens-Johnson Syndrome; Thalidomide; Tumor Necrosis Factor-alpha
PubMed: 35274741
DOI: 10.1002/14651858.CD013130.pub2 -
The Cochrane Database of Systematic... Mar 2022Steroids have been used widely since the early 1970s for the treatment of adult-onset minimal change disease (MCD). Recently, newer agents have been used in adult MCD... (Review)
Review
BACKGROUND
Steroids have been used widely since the early 1970s for the treatment of adult-onset minimal change disease (MCD). Recently, newer agents have been used in adult MCD aiming to reduce the risk of adverse effects. The response rates to immunosuppressive agents in adult MCD are more variable than in children. The optimal agent, dose, and duration of treatment for the first episode of nephrotic syndrome, or for disease relapse(s) have not been determined. This is an update of a review first published in 2008.
OBJECTIVES
We aimed to 1) evaluate the benefits and harms of different agents, including both immunosuppressive and non-immunosuppressive agents, in adults with MCD causing the nephrotic syndrome; and 2) evaluate the efficacy of interventions on 'time-to-remission' of nephrotic syndrome, in adults with MCD causing the nephrotic syndrome.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 21 July 2021 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 (RCTs) and quasi-RCTs of any intervention for MCD with nephrotic syndrome in adults over 18 years were included. Studies comparing different types, routes, frequencies, and duration of immunosuppressive agents and non-immunosuppressive agents were assessed.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and results were expressed as a risk ratio (RR) for dichotomous outcomes, or mean difference (MD) for continuous data with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Fifteen RCTs (769 randomised participants) were identified; four studies evaluated different prednisolone regimens, eight studies evaluated the calcineurin inhibitors (CNIs) (tacrolimus or cyclosporin), two studies evaluated enteric-coated mycophenolate sodium (EC-MPS) and one study evaluated levamisole. In all but two studies of non-corticosteroid agents, reduced-dose prednisolone was given with the treatment agent and the comparator was high-dose prednisolone. In the risk of bias assessment, 11 and seven studies were at low risk of bias for sequence generation and allocation concealment, respectively. No studies were at low risk of performance bias and eight studies were at low risk of detection bias. Thirteen, 10 and six studies were at low risk of attrition bias, reporting bias and other bias, respectively. Compared with no specific treatment, it is uncertain whether prednisolone increases the number with complete remission (1 study, 28 participants: RR 1.44, 95% CI 0.95 to 2.19), complete or partial remission (1 study, 28 participants: RR 1.38, 95% CI 0.98 to 1.95), subsequent relapse (1 study, 28 participants: RR 0.75, 95% CI 0.48 to 1.17), or reduces the adverse effects because the certainty of the evidence is very low. Compared with oral prednisolone alone, it is uncertain whether intravenous methylprednisolone and prednisolone increase the number with complete remission (2 studies, 35 participants: RR 1.76, 95% CI 0.17 to 18.32; I² = 90%), relapse (two studies, 19 participants. RR 1.18, 95% CI 0.65 to 2.15; I² = 0%) or adverse events because the certainty of the evidence is very low. Compared with prednisolone alone, CNIs with reduced-dose prednisolone or without prednisolone probably make little or no difference to the number achieving complete remission (8 studies; 492 participants: RR 0.99, 95% CI 0.93 to 1.05; I² = 0%), complete or partial remission (4 studies, 269 participants: RR 1.01, 95% CI 0.96 to 1.05; I² = 0%), or relapse (7 studies; 422 participants: RR 0.73, 95% CI 0.51 to 1.03; I² = 0%) (moderate certainty evidence), may reduce the risk of obesity or Cushing's Syndrome (5 studies; 388 participants: RR 0.11, 95% CI 0.02 to 0.59; I² = 45%) and the risk of acne (4 studies; 270 participants: RR 0.15, 95% CI 0.03 to 0.67; I² = 0%) (low certainty evidence); and had uncertain effects on diabetes or hyperglycaemia, hypertension, and acute kidney injury (AKI) (low certainty evidence). Compared with prednisolone alone, EC-MPS with reduced-dose prednisolone probably make little or no difference to the number undergoing complete remission at 4 weeks (1 study, 114 participants: RR 1.12, 95% CI 0.84 to 1.50), and at 24 weeks probably make little or no difference to the number undergoing complete remission (2 studies, 134 participants: RR 1.12, 95% CI 0.84 to 1.38; I² = 0%) (moderate certainty evidence), complete or partial remission (2 studies 134 participants: RR 0.92, 95% CI 0.75 to 1.12; I² = 0%), relapse (2 studies, 83 participants: RR 0.50, 95% CI 0.07 to 3.74; I² = 56%) (low certainty evidence); or to the adverse events of new-onset glucose intolerance, death, or AKI (low certainty evidence). One study (24 participants) compared levamisole and prednisolone with prednisolone in patients with relapsing disease. The authors identified no differences in mean relapse rate or adverse effects but no standard deviations were provided.
AUTHORS' CONCLUSIONS
This updated review has identified evidence for the efficacy and adverse effects of CNIs and EC-MPS with or without reduced-dose prednisolone compared with prednisolone alone for the induction of remission in adults with MCD and nephrotic syndrome with some reductions in steroid-associated adverse events. RCT data on the efficacy and adverse effects of rituximab in adults with MCD are awaited. Further, adequately powered RCTs are required to determine the relative efficacies of CNIs and EC-MPS and to evaluate these medications in patients with relapsing or steroid-resistant disease.
Topics: Acute Kidney Injury; Adult; Calcineurin Inhibitors; Child; Female; Humans; Immunosuppressive Agents; Levamisole; Male; Methylprednisolone; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Recurrence; Steroids
PubMed: 35230699
DOI: 10.1002/14651858.CD001537.pub5 -
Translational Cancer Research May 2021With the advent of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) treatment has become considered the appropriate...
BACKGROUND
With the advent of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) treatment has become considered the appropriate chemotherapy treatment for aggressive or advanced-stage indolent B-cell non-Hodgkins lymphoma (NHL). In recent years, RCHOP-14 seems to have achieved better outcomes in patients with aggressive or advanced-stage indolent B-cell NHL than RCHOP-21.
METHODS
To verify the befitting chemotherapy regimens for patients with B-cell NHL, we searched the electronic databases for relevant English-language literature published in January 2020. The primary outcomes were complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Six eligible Phase II and III randomized controlled clinical trials (RCTs) and two high-quality observational comparative studies (OCSs) were extracted, with 5,565 patients with B-cell NHL involved in the evaluation.
RESULTS
The analysis demonstrated no significant difference in RCHOP-14 and RCHOP-21 CR rates [odds ratio (OR) =0.98, 95% CI: 0.77-1.24, P=0.85]. Compared with RCHOP-21, the merged hazard ratio (HR) after treatment with RCHOP-14 for PFS and OS was 0.94 (95% CI: 0.84-1.06, P=0.32) and 0.91 (95% CI: 0.83-1.01, P=0.08), respectively. A subgroup analysis based on the international prognostic index (IPI) score showed that both chemotherapy regimens were applicable in B-cell NHL patients with different prognoses. The frequency of toxic side-effects was similar between schemes.
CONCLUSIONS
The data presented suggest that the efficacy and safety of both regimens are comparable and that RCHOP-14 remains a viable plan in patients with B-cell NHL who prefer a shorter therapy course.
PubMed: 35116526
DOI: 10.21037/tcr-20-3123 -
Daru : Journal of Faculty of Pharmacy,... Jun 2022Tocilizumab has shown equivocal outcomes in reducing mortality in COVID-19. The corticosteroids appear to be an affordable alternative to tocilizumab. This study aims to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Tocilizumab has shown equivocal outcomes in reducing mortality in COVID-19. The corticosteroids appear to be an affordable alternative to tocilizumab. This study aims to estimate the efficacy of tocilizumab and the corticosteroids particularly dexamethasone and methylprednisolone and to identify possible determinants of their efficacy.
METHODS
Five electronic databases were searched for studies involving tocilizumab, dexamethasone, and methylprednisolone in treating COVID-19. We included case-control and randomized or partially randomized trials. Meta-regression for patient baseline characteristics, co-medications, and tocilizumab dose regimens was performed to identify contributing factors to drug efficacy.
RESULTS
Thirteen randomized controlled trials (RCTs) and twenty-four case-control studies were included in our meta-analysis involving 18,702 patients. Meta-analysis among the RCTs showed that a summary estimate favoring mortality reduction (OR 0.71, 95%CI 0.55 - 0.92) contributed mainly by tocilizumab and dexamethasone. Among case-control studies, meta-analysis showed mortality reduction (OR 0.52, 95%CI 0.36 - 0.75) contributed by tocilizumab and tocilizumab-methylprednisolone combination. Methylprednisolone alone did not reduce mortality except for one study involving high dose pulse therapy. Meta-analysis also found that all three drugs did not significantly reduce mechanical ventilation (OR 0.72, 95%CI 0.32 - 1.60).
CONCLUSION
Tocilizumab and dexamethasone emerge as viable options in reducing mortality in severe COVID-19 patients. A tocilizumab-corticosteroid combination strategy may improve therapeutic outcome in cases where single therapy fails.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Dexamethasone; Humans; Methylprednisolone; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35084705
DOI: 10.1007/s40199-021-00430-8