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The Lancet. Microbe Nov 2023Randomised controlled trials of passive antibodies as treatment and prophylaxis for COVID-19 have reported variable efficacy. However, the determinants of efficacy have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Randomised controlled trials of passive antibodies as treatment and prophylaxis for COVID-19 have reported variable efficacy. However, the determinants of efficacy have not been identified. We aimed to assess how the dose and timing of administration affect treatment outcome.
METHODS
In this systematic review and meta-analysis, we extracted data from published studies of passive antibody treatment from Jan 1, 2019, to Jan 31, 2023, that were identified by searching multiple databases, including MEDLINE, PubMed, and ClinicalTrials.gov. We included only randomised controlled trials of passive antibody administration for the prevention or treatment of COVID-19. To compare administered antibody dose between different treatments, we used data on in-vitro neutralisation titres to normalise dose by antibody potency. We used mixed-effects regression and model fitting to analyse the relationship between timing, dose and efficacy.
FINDINGS
We found 58 randomised controlled trials that investigated passive antibody therapies for the treatment or prevention of COVID-19. Earlier clinical stage at treatment initiation was highly predictive of the efficacy of both monoclonal antibodies (p<0·0001) and convalescent plasma therapy (p=0·030) in preventing progression to subsequent stages, with either prophylaxis or treatment in outpatients showing the greatest effects. For the treatment of outpatients with COVID-19, we found a significant association between the dose administered and efficacy in preventing hospitalisation (relative risk 0·77; p<0·0001). Using this relationship, we predicted that no approved monoclonal antibody was expected to provide more than 30% efficacy against some omicron (B.1.1.529) subvariants, such as BQ.1.1.
INTERPRETATION
Early administration before hospitalisation and sufficient doses of passive antibody therapy are crucial to achieving high efficacy in preventing clinical progression. The relationship between dose and efficacy provides a framework for the rational assessment of future passive antibody prophylaxis and treatment strategies for COVID-19.
FUNDING
The Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council, the University of New South Wales, Monash University, Haematology Society of Australia and New Zealand, Leukaemia Foundation, and the Victorian Government.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Serotherapy; Australia; Treatment Outcome; Antibodies, Monoclonal
PubMed: 37924835
DOI: 10.1016/S2666-5247(23)00194-5 -
Medicine Dec 2023A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials.
INTRODUCTION
A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME).
MATERIALS AND METHODS
A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies.
RESULTS
A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD = -2.42, 95% CI [-3.93 to -0.90], P = .002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD = -22.41, 95% CI [-29.95 to -14.86], P < .00001) and the number of injections(MD = -0.93, 95% CI [-1.33 to -0.54], P < .00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events.
CONCLUSIONS
Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.
Topics: Antibodies, Bispecific; Vascular Endothelial Growth Factor A; Macular Degeneration; Humans; Randomized Controlled Trials as Topic; Macular Edema; Diabetes Complications; Treatment Outcome
PubMed: 38115358
DOI: 10.1097/MD.0000000000036370 -
Human Vaccines & Immunotherapeutics Dec 2023Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of the seroconversion rates and adverse effects of COVID-19 mRNA vaccine and COVID-19 viral vector vaccine in kidney transplant recipient patients.
Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse effects of additional different vaccinations in KTR patients in existing studies. Databases such as PubMed, Cochrane Library, Web of Science, Embase, ClinicalTrials.gov and others. Three high-quality RCT were included and showed no statistical difference in seroconversion rates between the two vaccines (RR = 0.93[0.76,1.13]). There was no statistical difference in seroconversion rates between the sexes, for men (RR = 0.93[0.69,1.25]) and women (RR = 0.91[0.62,1.33]). Among the adverse effects there was no statistically significant difference in fever (RR = 1.06[0.44,2.57]), while for injection site pain there was a statistically significant difference (RR = 1.14[1.18,1.84]). There was no significant difference in seroconversion rates in patients with KTR who received the two additional vaccines. Patients injected with the viral vector vaccine were less painful than those injected with the mRNA vaccine.
Topics: Female; Humans; Male; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Kidney Transplantation; Seroconversion; Vaccination
PubMed: 37057765
DOI: 10.1080/21645515.2023.2196893 -
Journal of Clinical Neuromuscular... Dec 2023Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle...
OBJECTIVES
Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research.
METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies.
RESULTS
We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases).
CONCLUSIONS
IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.
Topics: Male; Middle Aged; Humans; Female; Isaacs Syndrome; Thymoma; Anticonvulsants; Thymus Neoplasms; Autoantibodies; Potassium Channels, Voltage-Gated; Carbamazepine; Receptors, Cholinergic; Steroids; Recurrence
PubMed: 37962197
DOI: 10.1097/CND.0000000000000460 -
JNCI Cancer Spectrum Aug 2023Antibody-drug conjugates are attractive targeted agents in anticancer treatment because of their unique mechanism of action and reduced toxicity. Little is known about... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antibody-drug conjugates are attractive targeted agents in anticancer treatment because of their unique mechanism of action and reduced toxicity. Little is known about the spectrum of adverse events associated with antibody-drug conjugates, despite tens of clinical trials.
METHODS
A systematic review of randomized controlled trials evaluating antibody-drug conjugate efficacy in anticancer treatment was conducted. PubMed, EMBASE, and ClinicalTrial.gov were searched for relevant studies. Meta-analyses assessed the odds ratios (ORs) of 12 treatment-related symptoms and toxicities in patients treated with antibody-drug conjugates compared with those receiving other anticancer agents without antibody-drug conjugates. All-grade and high-grade (grade ≥3) toxicities were examined.
RESULTS
Twenty studies involving 10 075 patients were included. Compared with control groups, antibody-drug conjugates were associated with a higher risk of all-grade fatigue (OR = 1.25, 95% confidence interval [CI] = 1.08 to 1.45), anorexia (OR = 1.36, 95% CI = 1.09 to 1.69), nausea (OR = 1.46, 95% CI = 1.09 to 1.97), and sensory neuropathy (OR = 2.18, 95% CI = 1.27 to 3.76) as treatment-related symptoms. Patients treated with antibody-drug conjugates had a statistically significantly lower risk of all-grade febrile neutropenia (OR = 0.46, 95% CI = 0.22 to 0.96). Conversely, they had a higher risk of thrombocytopenia (OR = 2.07, 95% CI = 1.00 to 4.31), increased alanine aminotransferase (OR = 2.51, 95% CI = 1.84 to 3.40), and increased aspartate aminotransferase (OR = 2.83, 95% CI = 2.04 to 3.93). Subgroup analysis showed a similar toxicity profile when comparing the solid tumors with hematologic malignancy groups and the antibody-drug conjugate vs antibody-drug conjugate plus chemotherapy groups, except for some neurologic and hematologic adverse events.
CONCLUSIONS
This comprehensive profile of adverse events associated with antibody-drug conjugate-based treatment shows an increase in various types of all-grade treatment-related symptoms and adverse events, although no increase in high-grade adverse events was seen.
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Neoplasms
PubMed: 37756687
DOI: 10.1093/jncics/pkad069 -
American Journal of Clinical Dermatology May 2024The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain. (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain.
OBJECTIVE
The aim was to perform a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics and small-molecule inhibitors for the treatment of PP and PPP.
METHODS
MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for eligible studies from inception to May 13, 2023. This NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Network Meta-Analyses guidelines. Frequentist random-effects models NMA was performed with the surface under the cumulative ranking curve calculated for ranking. Our primary outcome was the proportion of patients achieving a clear/minimal Palmoplantar Psoriasis/Pustulosis Physician Global Assessment score (PPPGA 0/1 or PPPPGA 0/1) response at 12-16 weeks. Secondary outcomes consisted of the percentage of overall improvement in palmoplantar score and of improvement ≥ 75%, at 12-16 weeks.
RESULTS
The study comprised a total of 29 randomized controlled trials (RCTs), involving 4798 psoriasis patients with palmoplantar diseases. For PP, 16 RCTs with nine different treatments, including adalimumab, apremilast, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included for the analysis. In the NMA of PP, secukinumab 300 mg ranked highest (odds ratio [OR] 33.50, 95% confidence interval [CI] 4.37-256.86) in achieving PPPGA 0/1, followed by guselkumab 100 mg (OR 18.68, 95% CI 10.07-34.65). In the case of PPP, seven RCTs with six treatments, including apremilast, etanercept, guselkumab, imsidolimab, spesolimab, and ustekinumab, were included for the analysis. In the NMA of PPP, although no treatment demonstrated a significant difference compared to placebo in achieving PPPPGA 0/1, guselkumab 100 mg showed the greatest statistically significant improvement in the palmoplantar score (weighted mean difference 31.73, 95% CI 19.89-43.57) as a secondary outcome.
CONCLUSION
Among all available biologics and small-molecule inhibitors, secukinumab 300 mg and guselkumab 100 mg had the most favorable efficacy in treating PP and PPP, respectively.
Topics: Psoriasis; Humans; Biological Products; Network Meta-Analysis; Treatment Outcome; Dermatologic Agents; Randomized Controlled Trials as Topic; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Thalidomide
PubMed: 38438782
DOI: 10.1007/s40257-024-00849-0 -
Acta Neurologica Belgica Dec 2023We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people with multiple sclerosis (MS).
METHODS
The four databases including PubMed, Scopus, Embase, and Web of Science were comprehensively searched in April 2022. We defined PICO as follows. Problem or study population (P): patients with MS; intervention (I): Rituximab; comparison (C): none; outcome (O): efficacy and safety.
RESULTS
After two-step screening, a total of 27 studies entered into our qualitative and quantitative synthesis. Our analysis showed a significant decrease in EDSS score in all patients with MS after treatment (SMD: - 0.44, 95% CI - 0.85, - 0.03). In addition, the ARR was reduced after using rituximab compared to the pre-treatment period (SMD: - 0.65, 95% CI - 1.55, 0.24) but it was not significant. The most common side effect after rituximab with a pooled prevalence of 28.63% (95% CI 16.61%, 42.33%). Furthermore, the pooled prevalence of infection was 24% in patients with MS (95% CI 13%, 36%). In the end, the pooled prevalence of malignancies after rituximab treatment was 0.39% (95% CI 0.02%, 1.03%).
CONCLUSION
Our findings illustrated an acceptable safety for this treatment. However, further studies with randomized design, long follow-up, and large sample sizes are needed to confirm the safety and efficacy of rituximab in patients with MS.
Topics: Humans; Rituximab; Multiple Sclerosis; Antibodies, Monoclonal
PubMed: 37428437
DOI: 10.1007/s13760-023-02329-4 -
Critical Reviews in Oncology/hematology Dec 2023The advent of targeted therapies signaled novel avenues for more optimal oncological outcomes. Antibody-drug conjugates (ADCs) have risen as a cornerstone of the... (Review)
Review
BACKGROUND
The advent of targeted therapies signaled novel avenues for more optimal oncological outcomes. Antibody-drug conjugates (ADCs) have risen as a cornerstone of the ever-expanding targeted therapy era. The purpose of this systematic review is to delineate the rapidly evolving clinical landscape of ADCs for solid tumors.
METHODS
A literature search was performed in Medline, Embase and Cochrane databases for phase II and III clinical trials. Outcomes of interest were the objective response rate, overall survival, progression-free survival and adverse events.
RESULTS
A total of 92 clinical trials (76 phase II and 16 phase III) evaluated the efficacy and safety of ADCs for a plethora of solid tumors. Out of the 30 investigated ADCs, 8 have received approval by regulatory organizations for solid tumors. Currently, 52 phase III clinical trials for ADCs are ongoing.
CONCLUSION
ADCs have shown promising results for several solid tumors and various cancer settings.
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Neoplasms
PubMed: 37866413
DOI: 10.1016/j.critrevonc.2023.104189 -
Paediatric Drugs Sep 2023The use of ustekinumab in pediatric patients with inflammatory bowel disease (IBD) is off-label and the data are limited. We conducted a systematic review evaluating the...
BACKGROUND
The use of ustekinumab in pediatric patients with inflammatory bowel disease (IBD) is off-label and the data are limited. We conducted a systematic review evaluating the efficacy and safety of ustekinumab in pediatric IBD.
METHODS
We systematically searched PubMed, EMBASE and Cochrane databases for studies of ustekinumab in children and adolescents with IBD investigating clinical remission, clinical response, corticosteroid-free (CS-free) remission, endoscopic remission/response, or safety up to March 17, 2023. A random-effects model was used for calculating summary estimates.
RESULTS
Eleven studies, comprising 370 patients were included. For Crohn's disease (CD), the pooled clinical remission rates were 34% (73/204) at 8-16 weeks and 46% (60/129) at 1 year. The pooled CS-free clinical remission rates were 23% (10/44) at 8-16 weeks and 45% (42/96) at 1 year. For ulcerative colitis (UC)/IBD unspecified (IBD-U), the pooled CS-free clinical remission rates were 24% (6/25) at 26 weeks and 46% (16/35) at 1 year. Endoscopic remission was found in 0-37.5% of CD and 63.6% of UC. Serious adverse events were reported in 3.5% of patients. About one half of patients required reduction in dose intervals and 62.75% patients could continue ustekinumab therapy at 1 year or final visit.
CONCLUSIONS
According to low-quality evidence mainly from cohort studies and case series, approximately one half of patients with CD and UC/IBD-U achieved remission at 1 year. Ustekinumab has a reasonable safety profile and dose optimization is frequently required. Data on the long-term benefit and high-quality evidence are still needed.
Topics: Humans; Child; Adolescent; Ustekinumab; Remission Induction; Crohn Disease; Inflammatory Bowel Diseases; Colitis, Ulcerative
PubMed: 37528211
DOI: 10.1007/s40272-023-00586-7 -
European Journal of Neurology Oct 2023Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While... (Review)
Review
BACKGROUND
Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized.
METHODS
We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified.
RESULTS
A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1).
CONCLUSIONS
The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
Topics: Humans; Female; Male; Neuromyelitis Optica; Contrast Media; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Gadolinium; Aquaporin 4; Spinal Cord Diseases; Immunoglobulin G
PubMed: 37433584
DOI: 10.1111/ene.15983