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International Journal of Molecular... Mar 2024Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review,... (Review)
Review
Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review, following PRISMA-ScR guidelines, systematically identified and evaluated clinical studies on the impact of CD44 expression on chemotherapy treatment outcomes across various cancer types. The search encompassed PubMed (1985-2023) and SCOPUS (1936-2023) databases, yielding a total of 12,659 articles, of which 40 met the inclusion criteria and were included in the qualitative synthesis using a predefined data extraction table. Data collected included the cancer type, sample size, interventions, control, treatment outcome, study type, expression of CD44 variants and isoforms, and effect of CD44 on chemotherapy outcome. Most of the studies demonstrated an association between increased CD44 expression and negative chemotherapeutic outcomes such as shorter overall survival, increased tumor recurrence, and resistance to chemotherapy, indicating a potential role of CD44 upregulation in chemoresistance in cancer patients. However, a subset of studies also reported non-significant relationships or conflicting results. In summary, this scoping review highlighted the breadth of the available literature investigating the clinical association between CD44 and chemotherapeutic outcomes. Further research is required to elucidate this relationship to aid clinicians in managing CD44-positive cancer patients.
Topics: Humans; Drug Resistance, Neoplasm; Hyaluronan Receptors; Treatment Outcome
PubMed: 38542115
DOI: 10.3390/ijms25063141 -
Pharmacogenetics and Genomics Jul 2024This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal... (Review)
Review
PURPOSE
This umbrella review was conducted to summarize the association between HLA*1502 allele with antiepileptic induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
METHODS
Pubmed, Scopus and EMBASE were searched for eligible reviews in May 2023. Two authors independently screened titles and abstracts and assessed full-text reviews for eligibility. The quality of meta-analyses and case-control studies was appraised with Assessing the Methodological Quality of Systematic Reviews 2 and Newcastle-Ottawa Scale, respectively. Narrative summaries of each antiepileptic drug were analyzed. Preestablished protocol was registered on the International Prospective Register of Systematic Reviews Registry(ID: CRD42023403957).
RESULTS
Included studies are systematic reviews, meta-analyses and case-control studies evaluating the association of HLA-B*1502 allele with the following antiepileptics. Seven meta-analyses for carbamazepine, three meta-analyses for lamotrigine (LTG), three case-control studies for oxcarbazepine, nine case-control studies for phenytoin and four case-control studies for phenobarbitone were included. The findings of this umbrella review suggest that there is a strong association between HLA-B-1502 with SJS/TEN for carbamazepine and oxcarbazepine and a milder association for lamotrigine and phenytoin.
CONCLUSION
In summary, although HLA-B*1502 is less likely to be associated with phenytoin or lamotrigine-induced SJS/TEN compared to carbamazepine-induced SJS/TEN, it is a significant risk factor that if carefully screened, could potentially reduce the development of SJS/TEN. In view of potential morbidity and mortality, HLA-B*1502 testing may be beneficial in patients who are initiating lamotrigine/phenytoin therapy. However, further studies are required to examine the association of other alleles with the development of SJS/TEN and to explore the possibility of genome-wide association studies before initiation of treatment.
Topics: Stevens-Johnson Syndrome; Humans; Anticonvulsants; HLA-B15 Antigen; Carbamazepine; Lamotrigine; Genetic Predisposition to Disease; Alleles
PubMed: 38527170
DOI: 10.1097/FPC.0000000000000531 -
Molecular Biology Reports Mar 2024Schizophrenia constitutes a severe psychiatric disorder with detrimental impacts on individuals, their support systems, and the broader economy. Extensive research has...
Schizophrenia constitutes a severe psychiatric disorder with detrimental impacts on individuals, their support systems, and the broader economy. Extensive research has revealed a notable association between variations in the Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene and an increased susceptibility to schizophrenia.This study represents the first systematic review of the literature investigating the impact of CTLA-4 polymorphisms and expression on the development and progression of schizophrenia.Our investigation involved a comprehensive search strategy, using a combination of title, abstract, and MESH terms in four databases, including PubMed, Scopus, Web of Science, and Google Scholar, until August 29th, 2023. The complete texts of the identified records were obtained and rigorously assessed based on predefined exclusion and inclusion criteria. Out of the numerous records, a total of 88 were identified through the databases. 10 studies met the criteria; therefore, their quality was assessed and included in this systematic study. The records were then categorized into polymorphism and expression groups. Our investigation emphasizes an association between rs3087243, rs231779, rs231777, rs16840252, rs5742909, and rs231775 polymorphisms and the development of schizophrenia. The results demonstrate a correlation between CTLA-4 polymorphisms and schizophrenia, compelling the need for further research to thoroughly examine the role of CTLA-4 in schizophrenia and other psychiatric disorders.
Topics: Humans; CTLA-4 Antigen; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Schizophrenia
PubMed: 38520576
DOI: 10.1007/s11033-024-09299-7 -
Endocrine Practice : Official Journal... May 2024Teplizumab has emerged as a potential disease-modifying drug in type 1 diabetes (T1D). This meta-analysis sought to summarize the therapeutic effect of teplizumab in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Teplizumab has emerged as a potential disease-modifying drug in type 1 diabetes (T1D). This meta-analysis sought to summarize the therapeutic effect of teplizumab in newly diagnosed patients with T1D.
METHODS
Randomized controlled trials involving patients with T1D receiving teplizumab in the intervention arm and placebo (or no active intervention) in the control arm were searched throughout the electronic databases. The primary outcome was the change in area under the curve of C-peptide levels from baseline.
RESULTS
Seven reports from 6 studies involving 834 subjects met the inclusion criteria. Compared to teplizumab, greater reductions in area under the curve of C-peptide from the baseline values were observed in the control group after 6 months (mean difference [MD] 0.07 nmol/L [0.01, 0.13], P = .02), after 12 months (MD 0.07 nmol/L [0.04, 0.11], P = .0001), after 18 months (MD 0.10 nmol/L [0.06, 0.14], P < .00001), and after 24 months (MD 0.07 nmol/L [0.01, 0.14], P = .03) of interventions. Moreover, fewer patients treated with teplizumab had a decreased C-peptide response after 6 months (odds ratio [OR] 0.21), after 12 months (OR 0.17), after 18 months (OR 0.30), and after 24 months (OR 0.12) of treatment. The preservation of endogenous insulin production was supported by reduced use of exogenous insulin with maintenance of comparable glycemic control for up to 18 months post-treatment. Teplizumab imparted higher risks of grade 3 or higher adverse events, adverse events leading to study medication discontinuation, nausea, rash, and lymphopenia.
CONCLUSION
The results of the meta-analysis support teplizumab as a promising disease-modifying therapy for newly diagnosed T1D.
Topics: Diabetes Mellitus, Type 1; Humans; Antibodies, Monoclonal, Humanized; CD3 Complex; Randomized Controlled Trials as Topic; C-Peptide
PubMed: 38519028
DOI: 10.1016/j.eprac.2024.03.006 -
The Cochrane Database of Systematic... Mar 2024People affected by ulcerative colitis (UC) are interested in dietary therapies as treatments that can improve their health and quality of life. Prebiotics are a category... (Review)
Review
BACKGROUND
People affected by ulcerative colitis (UC) are interested in dietary therapies as treatments that can improve their health and quality of life. Prebiotics are a category of food ingredients theorised to have health benefits for the gastrointestinal system through their effect on the growth and activity of intestinal bacteria and probiotics.
OBJECTIVES
To assess the efficacy and safety of prebiotics for the induction and maintenance of remission in people with active UC.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP on 24 June 2023.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) on people with UC. We considered any type of standalone or combination prebiotic intervention, except those prebiotics combined with probiotics (known as synbiotics), compared to any control intervention. We considered interventions of any dose and duration.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
We included 9 RCTs involving a total of 445 participants. Study duration ranged from 14 days to 2 to 3 months for induction and 1 to 6 months for maintenance of remission. All studies were on adults. Five studies were on people with mild to moderate active disease, three in remission or mild activity, and one did not mention. We judged only one study as at low risk of bias in all areas. Two studies compared prebiotics with placebo for induction of remission. We cannot draw any conclusions about clinical remission (70% versus 67%; risk ratio (RR) 1.05, 95% confidence interval (CI) 0.57 to 1.94); clinical improvement (mean Rachmilewitz score on day 14 of 4.1 versus 4.5; mean difference (MD) -0.40, 95% CI -2.67 to 1.87); faecal calprotectin levels (mean faecal calprotectin on day 14 of 1211 μg/mL versus 3740 μg/mL; MD -2529.00, 95% CI -6925.38 to 1867.38); interleukin-8 (IL-8) levels (mean IL-8 on day 7 of 2.9 pg/mL versus 5.0 pg/mL; MD -2.10, 95% CI -4.93 to 0.73); prostaglandin E2 (PGE-2) levels (mean PGE-2 on day 7 of 7.1 ng/mL versus 11.5 ng/mL; MD -4.40, 95% CI -20.25 to 11.45); or withdrawals due to adverse events (21% versus 8%; RR 2.73, 95% CI 0.51 to 14.55). All evidence was of very low certainty. No other outcomes were reported. Two studies compared inulin and oligofructose 15 g with inulin and oligofructose 7.5 g for induction of remission. We cannot draw any conclusions about clinical remission (53% versus 12.5%; RR 4.27, 95% CI 1.07 to 16.96); clinical improvement (67% versus 25%; RR 2.67, 95% CI 1.06 to 6.70); total adverse events (53.5% versus 31%; RR 1.71, 95% CI 0.72 to 4.06); or withdrawals due to adverse events (13% versus 25%; RR 0.53, 95% CI 0.11 to 2.50). All evidence was of very low certainty. No other outcomes were reported. One study compared prebiotics and anti-inflammatory therapy with anti-inflammatory therapy alone for induction of remission. We cannot draw any conclusions about clinical improvement (mean Lichtiger score at 4 weeks of 6.2 versus 10.3; MD -4.10, 95% CI -8.14 to -0.06) or serum C-reactive protein (CRP) levels (mean CRP levels at 4 weeks 0.55 ng/mL versus 0.50 ng/mL; MD 0.05, 95% CI -0.37 to 0.47). All evidence was of very low certainty. No other outcomes were reported. Three studies compared prebiotics with placebo for maintenance of remission. There may be no difference between groups in rate of clinical relapse (44% versus 33%; RR 1.36, 95% CI 0.79 to 2.31), and prebiotics may lead to more total adverse events than placebo (77% versus 46%; RR 1.68, 95% CI 1.18 to 2.40). The evidence was of low certainty. We cannot draw any conclusions about clinical improvement (mean partial Mayo score at day 60 of 0.428 versus 1.625; MD -1.20, 95% CI -2.17 to -0.22); faecal calprotectin levels (mean faecal calprotectin level at day 60 of 214 μg/mL versus 304 μg/mL; MD -89.79, 95% CI -221.30 to 41.72); quality of life (mean Inflammatory Bowel Disease Questionnaire (IBDQ) score at day 60 of 193.5 versus 188.0; MD 5.50, 95% CI -8.94 to 19.94); or withdrawals due to adverse events (28.5% versus 11%; RR 2.57, 95% CI 1.15 to 5.73). The evidence for these outcomes was of very low certainty. No other outcomes were reported. One study compared prebiotics with synbiotics for maintenance of remission. We cannot draw any conclusions about quality of life (mean IBDQ score at 4 weeks 182.4 versus 176.1; MD 6.30, 95% CI -6.61 to 19.21) or withdrawals due to adverse events (23% versus 20%; RR 1.13, 95% CI 0.48 to 2.62). All evidence was of very low certainty. No other outcomes were reported. One study compared prebiotics with probiotics for maintenance of remission. We cannot draw any conclusions about quality of life (mean IBDQ score at 4 weeks 182.4 versus 168.6; MD 13.60, 95% CI 1.22 to 25.98) or withdrawals due to adverse events (22.5% versus 22.5%; RR 1.00, 95% CI 0.44 to 2.26). All evidence was of very low certainty. No other outcomes were reported.
AUTHORS' CONCLUSIONS
There may be no difference in occurrence of clinical relapse when adjuvant treatment with prebiotics is compared with adjuvant treatment with placebo for maintenance of remission in UC. Adjuvant treatment with prebiotics may result in more total adverse events when compared to adjuvant treatment with placebo for maintenance of remission. We could draw no conclusions for any of the other outcomes in this comparison due to the very low certainty of the evidence. The evidence for all other comparisons and outcomes was also of very low certainty, precluding any conclusions. It is difficult to make any clear recommendations for future research based on the findings of this review given the clinical and methodological heterogeneity among studies. It is recommended that a consensus is reached on these issues prior to any further research.
Topics: Adult; Humans; Anti-Inflammatory Agents; Colitis, Ulcerative; Interleukin-8; Inulin; Leukocyte L1 Antigen Complex; Prebiotics; Recurrence; Remission Induction
PubMed: 38501688
DOI: 10.1002/14651858.CD015084.pub2 -
Journal of Geriatric Oncology May 2024The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts.
MATERIALS AND METHODS
This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches.
RESULTS
The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01).
DISCUSSION
Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.
Topics: Aged; Humans; Age Factors; Antineoplastic Combined Chemotherapy Protocols; CTLA-4 Antigen; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; B7-H1 Antigen
PubMed: 38462434
DOI: 10.1016/j.jgo.2024.101741 -
Hepatology International Jun 2024The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for HBsAg seroclearance by pegylated interferon-α (PegIFNα) in patients with chronic HBV infection.
METHODS
A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science databases was conducted from their inception to 28 September 2022. Meta-analyses were performed following the PRISMA statement. Predictors of HBsAg seroclearance were evaluated based on baseline characteristics and on-treatment indicators.
RESULTS
This meta-analysis encompasses 27 studies, including a total of 7913 patients. The findings reveal several factors independently associated with HBsAg seroclearance induced by PegIFNα-based regimens. These factors include age (OR = 0.961), gender (male vs. female, OR = 0.537), genotype (A vs. B/D; OR = 7.472, OR = 10.738), treatment strategy (combination vs. monotherapy, OR = 2.126), baseline HBV DNA (OR = 0.414), baseline HBsAg (OR = 0.373), HBsAg levels at week 12 and 24 (OR = 0.384, OR = 0.294), HBsAg decline from baseline to week 12 and 24 (OR = 6.689, OR = 6.513), HBsAg decline from baseline ≥ 1 log IU/ml and ≥ 0.5 log IU/ml at week 12 (OR = 18.277; OR = 4.530), and ALT elevation at week 12 (OR = 3.622). Notably, subgroup analysis suggests no statistical association between HBsAg levels at week 12 and HBsAg seroclearance for treatment duration exceeding 48 weeks. The remaining results were consistent with the overall analysis.
CONCLUSIONS
This is the first meta-analysis to identify predictors of HBsAg seroclearance with PegIFNα-based regimens, including baseline and on-treatment factors, which is valuable in developing a better integrated predictive model for HBsAg seroclearance to guide individualized treatment and achieve the highest cost-effectiveness of PegIFNα.
Topics: Humans; Interferon-alpha; Hepatitis B, Chronic; Hepatitis B Surface Antigens; Antiviral Agents; Polyethylene Glycols; Hepatitis B virus
PubMed: 38461186
DOI: 10.1007/s12072-024-10648-8 -
European Journal of Cancer (Oxford,... May 2024Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival...
BACKGROUND
Overall survival (OS) is a universally accepted measure of clinical benefit; however, prolonged follow-up is needed to observe sufficient events. Disease-free survival (DFS) has been widely adopted as a primary endpoint for early breast cancer (EBC) trials, as follow-up is comparatively shorter. Here, we present an analysis evaluating DFS as a surrogate for OS for adjuvant treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) EBC.
METHODS
A systematic literature review which included randomized controlled trials (RCTs) with ≥80% of adult patients with HR+/HER2- EBC was conducted. The RCTs evaluated various systemic therapeutic categories; key inclusion criteria included reporting of DFS and OS hazard ratios (HRs) and mature OS data. Spearman rank correlation and weighted linear regression analyses evaluated DFS and OS HR correlation. A scenario analysis tested base-case analysis robustness, and a parallel analysis using patient-level data was conducted.
RESULTS
The base case (N = 14 RCTs) showed an unweighted Spearman coefficient of 0.81 between OS and DFS (weighted: 0.81), with 84% of the variability in OS explained by DFS differences (R from weighted regression). The surrogate threshold effect (Burzykowski T, Buyse M. Pharm Stat. 2006;5:173-186) was 0.82 for DFS/OS HR. Scenario analysis (n = 9 RCTs), which excluded chemotherapy trials, and patient-level analysis using FACE trial data were consistent with the base-case analysis.
CONCLUSIONS
These analyses support DFS as a reliable surrogate endpoint for OS in adjuvant HR+/HER2- EBC trials. Using DFS as a surrogate measure will permit timelier access to novel treatments for patients with HR+/HER2- EBC.
Topics: Adult; Humans; Female; Disease-Free Survival; Breast Neoplasms; Progression-Free Survival; Proportional Hazards Models; Chemotherapy, Adjuvant; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38460476
DOI: 10.1016/j.ejca.2024.113977 -
JAMA Network Open Mar 2024Immune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1)... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Immune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1) with response and survival in patients treated with ICIs is still controversial.
OBJECTIVES
To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs.
DATA SOURCES
PubMed, Embase, American Society of Clinical Oncology and European Society for Medical Oncology Meeting Libraries, and Web of Science were searched up to December 10, 2023.
STUDY SELECTION
Two authors independently screened the studies. Included studies were randomized and nonrandomized clinical trials enrolling patients with mUC receiving ICIs with available overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) data, separated between patients with PD-L1-positive and -negative tumors.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Two reviewers independently extracted data. Fixed- or random-effects models were used depending on the heterogeneity among the studies.
MAIN OUTCOMES AND MEASURES
Primary outcomes were odds ratios (ORs) for ORR and hazard ratios (HRs) for OS, comparing patients with PD-L1-positive tumors and patients with PD-L1-negative tumors. Secondary outcomes were the PFS HR between patients with PD-L1-positive and -negative tumors and OS HR between ICI arms and non-ICI arms of only randomized clinical trials.
RESULTS
A total of 14 studies were selected, comprising 5271 patients treated with ICIs (2625 patients had PD-L1-positive tumors). The ORR was 13.8% to 78.6% in patients with PD-L1-positive tumors and 5.1% to 63.2% in patients with PD-L1-negative tumors, with an association between PD-L1 status and ORR favoring patients with PD-L1-positive tumors (OR, 1.94; 95% CI, 1.47-2.56; P < .001). Median OS ranged from 8.4 to 24.1 months in patients with PD-L1-positive tumors and from 6.0 to 19.1 months in patients with PD-L1-negative tumors. The pooled HR showed a significant reduction for patients with PD-L1-positive tumors compared with those with PD-L1-negative tumors in the risk of death (HR, 0.71; 95% CI, 0.57-0.89; P = .003) and risk of progression (HR, 0.55; 95% CI, 0.44-0.69; P < .001) when ICIs were administered. PD-L1 is not likely to be a predictive biomarker of ICI response.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis suggests that PD-L1 expression is associated with improved ORR, OS, and PFS for patients with mUC who receive ICIs, but it is unlikely to be useful as a predictive biomarker. Developing predictive biomarkers is essential to select patients most likely to benefit from ICIs and avoid toxic effects and financial burden with these agents.
Topics: Humans; B7-H1 Antigen; Immune Checkpoint Inhibitors; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Biomarkers; Randomized Controlled Trials as Topic
PubMed: 38446479
DOI: 10.1001/jamanetworkopen.2024.1215 -
Journal of Neurology May 2024Myasthenia gravis (MG) is an autoimmune disease that causes local or generalized muscle weakness. Complement inhibitors and targeting of the neonatal Fc receptor (FcRn)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disease that causes local or generalized muscle weakness. Complement inhibitors and targeting of the neonatal Fc receptor (FcRn) to block IgG cycling are two novel and successful mechanisms.
METHODS
PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before May 18, 2023. Review Manager 5.3 software was used to assess the data.
RESULTS
We pooled 532 participants from six randomized controlled trials (RCTs). Compared to the placebo, the FcRn inhibitors were more efficacy in Myasthenia Gravis Activities of Daily Living (MG-ADL) (MD = - 1.69 [- 2.35, - 1.03], P < 0.00001), MG-ADL responder (RR = 2.01 [1.62, 2.48], P < 0.00001), Quantitative Myasthenia Gravis (QMG) (MD = - 2.45 [- 4.35, - 0.55], P = 0.01), Myasthenia Gravis Composite (MGC) (MD = - 2.97 [- 4.27, - 1.67], P < 0.00001), 15-item revised version of the Myasthenia Gravis Quality of Life (MGQoL15r) (MD = - 2.52 [- 3.54, - 1.50], P < 0.00001), without increasing the risk of safety. The subgroup analysis showed that efgartigimod was more effective than placebo in MG-ADL responders. Rozanolixizumab was more effective than the placebo except in QMG, and batoclimab was more effective than the placebo except in MG-ADL responder. Nipocalizumab did not show satisfactory efficacy in all outcomes. With the exception of rozanolixizumab, all drugs showed non-inferior safety profiles to placebo.
CONCLUSION
FcRn inhibitors have good efficacy and safety in patients with MG. Among them, efgartigimod and nipocalimab were effective without causing an increased safety risk. Rozanolixizumab, despite its superior efficacy, caused an increased incidence of adverse events. Current evidence does not suggest that nipocalimab is effective in patients with MG.
Topics: Myasthenia Gravis; Humans; Receptors, Fc; Histocompatibility Antigens Class I; Randomized Controlled Trials as Topic; Antibodies, Monoclonal, Humanized; Outcome Assessment, Health Care
PubMed: 38431900
DOI: 10.1007/s00415-024-12247-x