-
Journal For Immunotherapy of Cancer Aug 2023Immune-related adverse events (irAEs) are toxicities resulting from use of immune checkpoint inhibitors (ICIs). These side effects persist in some patients despite... (Review)
Review
Immune-related adverse events (irAEs) are toxicities resulting from use of immune checkpoint inhibitors (ICIs). These side effects persist in some patients despite withholding therapy and using immunosuppressive and immune-modulating agents. Little is known about chronic irAEs and they are felt to be rare. We performed a systematic review to characterize non-endocrine chronic irAEs reported in the literature and describe their management. Ovid MEDLINE and Embase databases were searched for reports of adult patients with solid cancers treated with ICIs who experienced chronic (>12 weeks) non-endocrine irAEs. Patient, treatment and toxicity data were collected. Of 6843 articles identified, 229 studies including 323 patients met our inclusion criteria. The median age was 65 (IQR 56-72) and 58% were male. Most patients (75%) had metastatic disease and the primary cancer site was melanoma in 43% and non-small cell lung cancer in 31% of patients. The most common ICIs delivered were pembrolizumab (24%) and nivolumab (37%). The chronic irAEs experienced were rheumatological in 20% of patients, followed by neurological in 19%, gastrointestinal in 16% and dermatological in 14%. The irAE persisted for a median (range) of 180 (84-2370) days and 30% of patients had ongoing symptoms or treatment. More than half (52%) of patients had chronic irAEs that persisted for >6 months. The ICI was permanently discontinued in 60% of patients and 76% required oral and/or intravenous steroids. This is the first systematic review to assess and report on moderate/severe chronic non-endocrine irAEs after treatment with ICI in the literature. These toxicities persisted for months-years and the majority required discontinuation of therapy and initiation of immunosuppression. Further research is needed to better understand chronic irAEs, which hold potential substantial clinical significance considering the expanded use of ICIs and their integration into the (neo)adjuvant settings.
Topics: Adult; Humans; Male; Aged; Female; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Antineoplastic Agents, Immunological; Nivolumab
PubMed: 37536939
DOI: 10.1136/jitc-2022-006500 -
International Journal of Radiation... Jan 2024Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains... (Review)
Review
A Systematic Review Informing the Management of Symptomatic Brain Radiation Necrosis After Stereotactic Radiosurgery and International Stereotactic Radiosurgery Society Recommendations.
Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains unclear. Our objective was to summarize the literature specific to efficacy and toxicity of treatment paradigms for patients with symptomatic corticosteroid-refractory RN and to provide consensus guidelines for grading and management of RN on behalf of the International Stereotactic Radiosurgery Society. A systematic review of articles pertaining to treatment of RN with bevacizumab, laser interstitial thermal therapy (LITT), surgical resection, or hyperbaric oxygen therapy was performed. The primary composite outcome was clinical and/or radiologic stability/improvement (ie, proportion of patients achieving improvement or stability with the given intervention). Proportions of patients achieving the primary outcome were pooled using random weighted-effects analysis but not directly compared between interventions. Twenty-one articles were included, of which only 2 were prospective studies. Thirteen reports were relevant for bevacizumab, 5 for LITT, 5 for surgical resection and 1 for hyperbaric oxygen therapy. Weighted effects analysis revealed that bevacizumab had a pooled symptom improvement/stability rate of 86% (95% CI 77%-92%), pooled T2 imaging improvement/stability rate of 93% (95% CI 87%-98%), and pooled T1 postcontrast improvement/stability rate of 94% (95% CI 87%-98%). Subgroup analysis showed a statistically significant improvement favoring treatment with low-dose (below median, ≤7.5 mg/kg every 3 weeks) versus high-dose bevacizumab with regards to symptom improvement/stability rate (P = .02) but not for radiologic T1 or T2 changes. The pooled T1 postcontrast improvement/stability rate for LITT was 88% (95% CI 82%-93%), and pooled symptom improvement/stability rate for surgery was 89% (95% CI 81%-96%). Toxicity was inconsistently reported but was generally low for all treatment paradigms. Corticosteroid-refractory RN that does not require urgent surgical intervention, with sufficient noninvasive diagnostic testing that favors RN, can be treated medically with bevacizumab in carefully selected patients as a strong recommendation. The role of LITT is evolving as a less invasive image guided surgical modality; however, the overall evidence for each modality is of low quality. Prospective head-to-head comparisons are needed to evaluate the relative efficacy and toxicity profile among treatment approaches.
Topics: Humans; Radiosurgery; Bevacizumab; Prospective Studies; Brain Neoplasms; Brain; Radiation Injuries; Necrosis; Adrenal Cortex Hormones; Retrospective Studies
PubMed: 37482137
DOI: 10.1016/j.ijrobp.2023.07.015 -
ESMO Open Aug 2023Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd.
MATERIALS AND METHODS
We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software.
RESULTS
We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%).
CONCLUSIONS
In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.
Topics: Humans; Middle Aged; Female; Breast Neoplasms; Cardiotoxicity; Incidence; Stroke Volume; Ventricular Function, Left; Lung Diseases, Interstitial
PubMed: 37481956
DOI: 10.1016/j.esmoop.2023.101613 -
Frontiers in Endocrinology 2023Hashimoto's thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hashimoto's thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other gluten-related conditions (GRC). In the last years, interest about gluten-free diet (GFD) has increased for its supposed extraintestinal anti-inflammatory effect; thus, many patients with HT initiate GFD on their own.
OBJECTIVES
The aim of this meta-analysis is to examine all available data in literature about the effect of a GFD on TgAb, TPOAb, TSH, FT4, and FT3 levels in patients with HT and no symptoms or histology of CD.
METHODS
The study was conducted according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology). The search was performed on databases PubMed and Scopus. The last search was performed on 7 February 2023. Quality assessment was performed. Meta-analyses were performed using the random-effect model. Hedges' was used to measure the effect size (ES). Statistical analyses were performed using StataSE 17.
RESULTS
The online search retrieved 409 articles, and 4 studies with a total of 87 patients were finally included for quantitative analysis. The risk of bias was generally low. The mean period of GFD was almost 6 months. The meta-analyses showed reduction in antibody levels with ES: -0.39 for TgAb (95% CI: -0.81 to +0.02; = 0.06; ² = 46.98%) and -0.40 for TPOAb (95% CI: -0.82 to +0.03; = 0.07; ² = 47.58%). TSH showed a reduction with ES: -0.35 (95% CI: -0.64 to -0.05; = 0.02; ² = 0%) and FT4 showed an increase with ES: +0.35% (95% CI: 0.06 to 0.64; = 0.02; ² = 0%). FT3 did not display variations (ES: 0.05; 95% CI: -0.38 to +0.48; = 0.82; ² = 51%). The heterogeneity of TgAb, TPOAb, and FT3 data was solved performing sub-analyses between patients with or without GRC (TgAb = 0.02; TPOAb = 0.02; FT3 = 0.04) and only for FT3, performing a sub-analysis between patients taking and not taking LT4 ( = 0.03).
CONCLUSION
This is the first meta-analysis investigating the effect of GFD on HT. Our results seem to indicate a positive effect of the gluten deprivation on thyroid function and its inflammation, particularly in patients with HT and GRC. However, current lines of evidence are not yet sufficient to recommend this dietary approach to all patients with a diagnosis of HT.
Topics: Humans; Thyroiditis, Autoimmune; Diet, Gluten-Free; Celiac Disease; Autoantibodies; Hashimoto Disease; Thyrotropin
PubMed: 37554764
DOI: 10.3389/fendo.2023.1200372 -
European Journal of Medical Research Nov 2023Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on January 22, 2023. We performed this systematic review and meta-analysis to assess the efficacy and safety of FDA-approved anti-amyloid-β (anti-Aβ) monoclonal antibodies (mabs) for the treatment of AD.
METHOD
PubMed, Embase, and Cochrane Library were systematically searched to identify relevant studies published before May 2023. Efficacy outcomes included Aβ, neuroimaging, and biomarker outcomes. Safety outcomes included amyloid-related imaging abnormalities with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H). Review Manager 5.4 software was used to assess the data. The standard mean differences (SMDs) or odds ratio (OR) with 95% confidence interval (95% CI) were analyzed and calculated with a random effect model or a fixed effect model.
RESULT
Overall, 4471 patients from 6 randomized controlled trials (RCTs), with 2190 patients in the treatment group and 2281 patients in the placebo group meeting the inclusion criteria. FDA-approved anti-Aβ mabs showed statistically significant improvements in clinical outcomes, including CDR-SB (P = 0.01), ADCS-ADL-MCI (P = 0.00003), ADCOMS (P < 0.00001), ADAS-Cog (P < 0.00001). Moreover, FDA-approved anti-Aβ mabs increased cerebrospinal fluid (CSF) Aβ1-42 (P = 0.002) and plasma Aβ42/40 ratios (P = 0.0008). They also decreased CSF P-Tau (P < 0.00001), CSF T-Tau (P < 0.00001), and plasma p-tau181 (P < 0.00001). FDA-approved anti-Aβ mabs perform neuroimaging changes in amyloid Positron Emission Tomography Standardized Uptake Value ratio (PET SUVr) (P < 0.00001). However, compared with placebo, FDA-approved anti-Aβ mabs had higher risk of ARIA-E (P < 0.00001) and ARIA-H (P < 0001).
CONCLUSION
FDA-approved anti-Aβ mabs have a role in slowing disease progression in patients with AD, at the cost of an increased probability of side effects.
Topics: United States; Humans; Alzheimer Disease; United States Food and Drug Administration; Randomized Controlled Trials as Topic; Amyloid beta-Peptides; Biomarkers
PubMed: 38017568
DOI: 10.1186/s40001-023-01512-w -
Annals of Family Medicine 2024We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia.
METHODS
We searched PubMed, Cochrane CENTRAL, and 5 trial registries, as well as the reference lists of identified studies. We included randomized controlled trials comparing a monoclonal antibody with placebo at a dose consistent with that used in phase 3 trials or for Food and Drug Administration approval. Studies had to report at least 1 clinically relevant benefit or harm. Data were extracted independently by at least 2 researchers for random effects meta-analysis. Changes in cognitive and functional scales were compared between groups, and each difference was assessed to determine if it met the minimal clinically important difference (MCID).
RESULTS
We identified 19 publications with 23,202 total participants that evaluated 8 anti-amyloid antibodies. There were small improvements over placebo in the Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 to -14 score (standardized mean difference = -0.07; 95% CI, -0.10 to -0.04), Mini Mental State Examination score (0.32 points; 95% CI, 0.13 to 0.50), and Clinical Dementia Rating-Sum of Boxes scale score (mean difference =-0.18 points; 95% CI, -0.34 to -0.03), and the combined functional scores (standardized mean difference = 0.09; 95% CI, 0.05 to 0.13). None of the changes, including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. Harms included significantly increased risks of amyloid-related imaging abnormalities (ARIA)-edema (relative risk [RR] = 10.29; number needed to harm [NNH] = 9), ARIA-hemorrhage (RR = 1.74; NNH = 13), and symptomatic ARIA-edema (RR = 24.3; NNH = 86).
CONCLUSIONS
Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.
Topics: United States; Humans; Alzheimer Disease; Antibodies, Monoclonal; Mental Status and Dementia Tests; Edema; Antibodies, Monoclonal, Humanized
PubMed: 38253509
DOI: 10.1370/afm.3050 -
Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
The Cochrane Database of Systematic... Jan 2024Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015.
OBJECTIVES
To compare the efficacy and safety, through network meta-analysis, of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1-a and beta 1-b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS.
SEARCH METHODS
CENTRAL, MEDLINE, Embase, and two trials registers were searched on 21 September 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. A top-up search was conducted on 8 August 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies and extracted data. We considered both direct and indirect evidence and performed data synthesis by pairwise and network meta-analysis. Certainty of the evidence was assessed by the GRADE approach.
MAIN RESULTS
We included 50 studies involving 36,541 participants (68.6% female and 31.4% male). Median treatment duration was 24 months, and 25 (50%) studies were placebo-controlled. Considering the risk of bias, the most frequent concern was related to the role of the sponsor in the authorship of the study report or in data management and analysis, for which we judged 68% of the studies were at high risk of other bias. The other frequent concerns were performance bias (34% judged as having high risk) and attrition bias (32% judged as having high risk). Placebo was used as the common comparator for network analysis. Relapses over 12 months: data were provided in 18 studies (9310 participants). Natalizumab results in a large reduction of people with relapses at 12 months (RR 0.52, 95% CI 0.43 to 0.63; high-certainty evidence). Fingolimod (RR 0.48, 95% CI 0.39 to 0.57; moderate-certainty evidence), daclizumab (RR 0.55, 95% CI 0.42 to 0.73; moderate-certainty evidence), and immunoglobulins (RR 0.60, 95% CI 0.47 to 0.79; moderate-certainty evidence) probably result in a large reduction of people with relapses at 12 months. Relapses over 24 months: data were reported in 28 studies (19,869 participants). Cladribine (RR 0.53, 95% CI 0.44 to 0.64; high-certainty evidence), alemtuzumab (RR 0.57, 95% CI 0.47 to 0.68; high-certainty evidence) and natalizumab (RR 0.56, 95% CI 0.48 to 0.65; high-certainty evidence) result in a large decrease of people with relapses at 24 months. Fingolimod (RR 0.54, 95% CI 0.48 to 0.60; moderate-certainty evidence), dimethyl fumarate (RR 0.62, 95% CI 0.55 to 0.70; moderate-certainty evidence), and ponesimod (RR 0.58, 95% CI 0.48 to 0.70; moderate-certainty evidence) probably result in a large decrease of people with relapses at 24 months. Glatiramer acetate (RR 0.84, 95%, CI 0.76 to 0.93; moderate-certainty evidence) and interferon beta-1a (Avonex, Rebif) (RR 0.84, 95% CI 0.78 to 0.91; moderate-certainty evidence) probably moderately decrease people with relapses at 24 months. Relapses over 36 months findings were available from five studies (3087 participants). None of the treatments assessed showed moderate- or high-certainty evidence compared to placebo. Disability worsening over 24 months was assessed in 31 studies (24,303 participants). Natalizumab probably results in a large reduction of disability worsening (RR 0.59, 95% CI 0.46 to 0.75; moderate-certainty evidence) at 24 months. Disability worsening over 36 months was assessed in three studies (2684 participants) but none of the studies used placebo as the comparator. Treatment discontinuation due to adverse events data were available from 43 studies (35,410 participants). Alemtuzumab probably results in a slight reduction of treatment discontinuation due to adverse events (OR 0.39, 95% CI 0.19 to 0.79; moderate-certainty evidence). Daclizumab (OR 2.55, 95% CI 1.40 to 4.63; moderate-certainty evidence), fingolimod (OR 1.84, 95% CI 1.31 to 2.57; moderate-certainty evidence), teriflunomide (OR 1.82, 95% CI 1.19 to 2.79; moderate-certainty evidence), interferon beta-1a (OR 1.48, 95% CI 0.99 to 2.20; moderate-certainty evidence), laquinimod (OR 1.49, 95 % CI 1.00 to 2.15; moderate-certainty evidence), natalizumab (OR 1.57, 95% CI 0.81 to 3.05), and glatiramer acetate (OR 1.48, 95% CI 1.01 to 2.14; moderate-certainty evidence) probably result in a slight increase in the number of people who discontinue treatment due to adverse events. Serious adverse events (SAEs) were reported in 35 studies (33,998 participants). There was probably a trivial reduction in SAEs amongst people with RRMS treated with interferon beta-1b as compared to placebo (OR 0.92, 95% CI 0.55 to 1.54; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
We are highly confident that, compared to placebo, two-year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. We are moderately confident that a two-year treatment with natalizumab may slow disability progression. Compared to those on placebo, people with RRMS treated with most of the assessed DMTs showed a higher frequency of treatment discontinuation due to AEs: we are moderately confident that this could happen with fingolimod, teriflunomide, interferon beta-1a, laquinimod, natalizumab and daclizumab, while our certainty with other DMTs is lower. We are also moderately certain that treatment with alemtuzumab is associated with fewer discontinuations due to adverse events than placebo, and moderately certain that interferon beta-1b probably results in a slight reduction in people who experience serious adverse events, but our certainty with regard to other DMTs is lower. Insufficient evidence is available to evaluate the efficacy and safety of DMTs in a longer term than two years, and this is a relevant issue for a chronic condition like MS that develops over decades. More than half of the included studies were sponsored by pharmaceutical companies and this may have influenced their results. Further studies should focus on direct comparison between active agents, with follow-up of at least three years, and assess other patient-relevant outcomes, such as quality of life and cognitive status, with particular focus on the impact of sex/gender on treatment effects.
Topics: Adult; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Glatiramer Acetate; Interferon beta-1a; Fingolimod Hydrochloride; Natalizumab; Interferon beta-1b; Cladribine; Alemtuzumab; Dimethyl Fumarate; Daclizumab; Network Meta-Analysis; Immunologic Factors; Recurrence
PubMed: 38174776
DOI: 10.1002/14651858.CD011381.pub3 -
Medicine Oct 2023Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as... (Meta-Analysis)
Meta-Analysis
Comparative of the effectiveness and safety of biological agents, small molecule drugs, and microbiome therapies in ulcerative colitis: Systematic review and network meta-analysis.
BACKGROUND
Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as new treatments for ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics, small-molecule drugs, and microbiome therapies for the treatment of patients with moderate-to-severe ulcerative colitis.
METHODS
We searched the Cochrane, Embase, and PubMed databases from their inception to December 2022. RCTs that recruited patients with moderate-to-severe ulcerative colitis treated with biological agents, small-molecule drugs, and microbiome therapies. Efficacy outcomes were induction of clinical remission and mucosal healing; safety outcomes were adverse events and serious adverse events. A network meta-analysis with multivariate consistency model random-effect meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety.
RESULTS
A total of 31 RCTs comprising 7933 UC patients were included in our studies. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib ranked highest for induction of clinical remission (SUCRA, 0.83) and mucosal healing (SUCRA, 0.44). Moreover, no treatments were found to increase the occurrence of adverse events compared with placebos. Ustekinumab ranked lowest for adverse events (SUCRA 0.26) and probiotic ranked lowest for serious adverse events (0·21), whereas tofacitinib ranked highest for adverse events (0·43) and upadacitinib ranked highest for serious adverse events (0·43).
CONCLUSION
In this systematic review and network meta-analysis, we found upadacitinib to be ranked highest for the induction of clinical remission and mucosal healing, but the worst performing agent in terms of adverse events in UC patients. Probiotics were the best-performing agent for safety outcomes. More trials of direct comparisons are needed to inform clinical decision-making with greater confidence.
Topics: Humans; Biological Factors; Colitis, Ulcerative; Network Meta-Analysis; Ustekinumab; Biological Products
PubMed: 37904440
DOI: 10.1097/MD.0000000000035689 -
BMC Cancer Aug 2023Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast... (Meta-Analysis)
Meta-Analysis
Neoadjuvant immunotherapy and chemotherapy regimens for the treatment of high-risk, early-stage triple-negative breast cancer: a systematic review and network meta-analysis.
BACKGROUND
Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast cancer patients. Recently, neoadjuvant delivery of the programmed cell death protein-1 inhibitor pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was approved for patients with high-risk, early-stage TNBC, but this treatment regimen has not been evaluated in head-to-head trials with other neoadjuvant treatment regimens. Therefore, the objective of this study was to estimate the relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab versus other neoadjuvant treatments for early-stage TNBC through a systematic review and network meta-analysis (NMA).
METHODS
EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts, and clinical trial registries were searched for randomized controlled trials evaluating neoadjuvant treatments for early-stage TNBC. NMA was performed to estimate relative treatment effects among evaluated interventions.
RESULTS
Five trials met the inclusion criteria and were included in the NMA. The relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab was favorable to paclitaxel followed by anthracycline + cyclophosphamide in terms of pathologic complete response (pCR), event-free survival (EFS), and overall survival; paclitaxel + carboplatin followed by anthracycline + cyclophosphamide in terms of pCR and EFS; paclitaxel + bevacizumab followed by anthracycline + cyclophosphamide + bevacizumab in terms of pCR; and paclitaxel + carboplatin + veliparib followed by anthracycline + cyclophosphamide in terms of EFS.
CONCLUSIONS
Neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab confers benefits in response and survival outcomes versus alternative neoadjuvant treatments for early-stage TNBC.
Topics: Humans; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Network Meta-Analysis; Bevacizumab; Carboplatin; Neoplasm Recurrence, Local; Immunotherapy; Adjuvants, Immunologic; Anthracyclines; Cyclophosphamide; Paclitaxel
PubMed: 37612624
DOI: 10.1186/s12885-023-11293-4