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Journal of the European Academy of... Jun 2021Alopecia areata is the third most common cause of dermatology consultations in children but the treatment of paediatric alopecia areata remains challenging. A systematic... (Review)
Review
Alopecia areata is the third most common cause of dermatology consultations in children but the treatment of paediatric alopecia areata remains challenging. A systematic review of the literature about the treatment of alopecia areata in children (≤18 years old) was performed on 11 May 2020 by searching the PubMed, Scopus and EBSCO databases. The terms used for the search were: 'alopecia areata', 'alopecia totalis' or 'alopecia universalis' combined with 'paediatric', 'children' or 'childhood'. A total of 89 articles were included in final evaluation. The most commonly assessed treatment options in paediatric alopecia areata were topical immunotherapy (response rate in monotherapy: 54%; 187/345) intralesional glucocorticosteroids (75%; 211/280), systemic glucocorticosteroids (73%; 102/140), and anthralin (42%; 31/74). Topical glucocorticosteroids (81%; 35/43), systemic Janus kinase (JAK) inhibitors (90%; 27/30), topical calcineurin inhibitors (42%; 8/19), topical JAK inhibitors (65%; 11/17), PUVA therapy (56%; 9/16) and 308-nm excimer laser (77%; 10/13) were also evaluated. Additionally, evaluation in smaller numbers of paediatric patients included methotrexate (100%; 10/10), topical minoxidil (44%; 4/9) and cyclosporine (83%; 5/6). There were limited data considering children with alopecia areata treated with azathioprine, hydroxychloroquine, topical sildenafil, topical prostaglandin analogues, fractional carbon dioxide laser, leflunomide, mesalazine, apremilast, dupilumab, ustekinumab, efalizumab, botulinum toxin, and compound glycyrrhizin. On the basis of the limited data available glucocorticosteroids (systemic, intralesional or topical) and JAK inhibitors (systemic or topical) may be considered the best documented and most effective treatment options in alopecia areata in children. There are no sufficient paediatric data to compare treatment safety and relapse rates in these therapeutic modalities.
Topics: Adolescent; Alopecia; Alopecia Areata; Child; Humans; Janus Kinase Inhibitors; Leflunomide; Minoxidil; Treatment Outcome
PubMed: 33630354
DOI: 10.1111/jdv.17187 -
Annals of the Rheumatic Diseases Jan 2021Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the...
OBJECTIVES
Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety.
METHODS
Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration.
RESULTS
The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale.
CONCLUSION
The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.
Topics: Adamantane; Advisory Committees; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azetidines; Cytokines; Drug Therapy, Combination; Europe; Heterocyclic Compounds, 3-Ring; Humans; Inflammatory Bowel Diseases; Janus Kinase Inhibitors; Niacinamide; Piperidines; Psoriasis; Purines; Pyrazoles; Pyridines; Pyrimidines; Rheumatology; Spondylarthropathies; Spondylitis, Ankylosing; Sulfonamides; Triazoles
PubMed: 33158881
DOI: 10.1136/annrheumdis-2020-218398 -
BMJ (Clinical Research Ed.) Jul 2020To compare the effects of treatments for coronavirus disease 2019 (covid-19). (Comparative Study)
Comparative Study
OBJECTIVE
To compare the effects of treatments for coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis.
DATA SOURCES
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.
STUDY SELECTION
Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
METHODS
After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
RESULTS
463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).
CONCLUSION
Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol is publicly available in the supplementary material.
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; COVID-19; Centers for Disease Control and Prevention, U.S.; China; Coronavirus Infections; Databases, Factual; Drug Combinations; Evidence-Based Medicine; Glucocorticoids; Humans; Hydroxychloroquine; Lopinavir; Network Meta-Analysis; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Respiration, Artificial; Ritonavir; SARS-CoV-2; Severity of Illness Index; Standard of Care; Treatment Outcome; United States; COVID-19 Drug Treatment
PubMed: 32732190
DOI: 10.1136/bmj.m2980 -
The Cochrane Database of Systematic... Jun 2021It remains unclear whether people with non-muscle invasive bladder cancer (NMIBC) benefit from intravesical gemcitabine compared to other agents in the primary or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It remains unclear whether people with non-muscle invasive bladder cancer (NMIBC) benefit from intravesical gemcitabine compared to other agents in the primary or recurrent setting following transurethral resection of a bladder tumor. This is an update of a Cochrane Review first published in 2012. Since that time, several randomized controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To assess the comparative effectiveness and toxicity of intravesical gemcitabine instillation for NMIBC.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Library, MEDLINE, Embase, four other databases, trial registries, and conference proceedings to 11 September 2020, with no restrictions on the language or status of publication.
SELECTION CRITERIA
We included RCTs in which participants received intravesical gemcitabine for primary or recurrent NMIBC.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the included studies and extracted data for the primary outcomes: time to recurrence, time to progression, grade III to V adverse events determined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0), and the secondary outcomes: time to death from bladder cancer, time to death from any cause, grade I or II adverse events determined by the CTCAE v5.0 and disease-specific quality of life. We performed statistical analyses using a random-effects model and rated the certainty of the evidence using GRADE.
MAIN RESULTS
We included seven studies with 1222 participants with NMIBC across five comparisons. This abstract focuses on the primary outcomes of the three most clinically relevant comparisons. 1. Gemcitabine versus saline: based on two years' to four years' follow-up, gemcitabine may reduce the risk of recurrence over time compared to saline (39% versus 47% recurrence rate, hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.54 to 1.09; studies = 2, participants = 734; I = 49%; low-certainty evidence), but the CI included the possibility of no effect. Gemcitabine may result in little to no difference in the risk of progression over time compared to saline (4.6% versus 4.8% progression rate, HR 0.96, 95% CI 0.19 to 4.71; studies = 2, participants = 654; I = 53%; low-certainty evidence). Gemcitabine may result in little to no difference in the CTCAE grade III to V adverse events compared to saline (5.9% versus 4.7% adverse events rate, risk ratio [RR] 1.26, 95% CI 0.58 to 2.75; studies = 2, participants = 668; I = 24%; low-certainty evidence). 2. Gemcitabine versus mitomycin: based on three years' follow-up (studies = 1, participants = 109), gemcitabine may reduce the risk of recurrence over time compared to mitomycin (17% versus 40% recurrence rate, HR 0.36, 95% CI 0.19 to 0.69; low-certainty evidence). Gemcitabine may reduce the risk of progression over time compared to mitomycin (11% versus 18% progression rate, HR 0.57, 95% CI 0.32 to 1.01; low-certainty evidence), but the CI included the possibility of no effect. We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to mitomycin (RR 0.51, 95% CI 0.13 to 1.93; very low-certainty evidence). The analysis was only based on recurrent NMIBC. 3. Gemcitabine versus Bacillus Calmette-Guérin (BCG) for recurrent (one-course BCG failure) high-risk NMIBC: based on 6 months' to 22 months' follow-up (studies = 1, participants = 80), gemcitabine may reduce the risk of recurrence compared to BCG (41% versus 97% recurrence rate, HR 0.15, 95% CI 0.09 to 0.26; low-certainty evidence) and progression over time (16% versus 33% progression rate, HR 0.45, 95% CI 0.27 to 0.76; low-certainty evidence). We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to BCG (RR 1.00, 95% CI 0.21 to 4.66; very low-certainty evidence). In addition, the review provides information on the comparison of gemcitabine versus BCG and gemcitabine versus one-third dose BCG. AUTHORS' CONCLUSIONS: Based on findings of this review, gemcitabine may have a more favorable impact on recurrence and progression-free survival than mitomycin but we are very uncertain as to how major adverse events compare. The same is true when comparing gemcitabine to BCG in individuals with high risk disease who have previously failed BCG. The underlying low- to very low-certainty evidence indicates that our confidence in these results is limited; the true effects may be substantially different from these findings; therefore, better quality studies are needed.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; BCG Vaccine; Bias; Cause of Death; Confidence Intervals; Deoxycytidine; Disease Progression; Drug Administration Schedule; Humans; Mitomycin; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Saline Solution; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 34125951
DOI: 10.1002/14651858.CD009294.pub3 -
JAMA Oct 2023Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.
OBJECTIVE
To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.
STUDY SELECTION
Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).
MAIN OUTCOMES AND MEASURES
Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.
RESULTS
Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).
CONCLUSIONS AND RELEVANCE
Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.
Topics: Adult; Humans; Cough; Pyrimidines; Quality of Life; Sulfonamides; Dose-Response Relationship, Drug; Treatment Outcome; Chronic Disease; Taste
PubMed: 37694849
DOI: 10.1001/jama.2023.18035 -
Journal of Drugs in Dermatology : JDD Jan 2022Actinic Keratosis (AK) is a premalignant lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Topical 5-Fluorouracil (5-FU) and imiquimod have been used...
BACKGROUND
Actinic Keratosis (AK) is a premalignant lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Topical 5-Fluorouracil (5-FU) and imiquimod have been used for field-directed therapy for AK; however, their use is limited by intolerable skin reactions and long treatment durations.
OBJECTIVE
To assess current data on the efficacy, tolerability, and long-term effectiveness of topical calcipotriol plus 5-FU combination for the field-directed therapy of AK. The systematic review will include a critical evaluation of the available evidence.
METHODS
A systematic review of the literature was performed in August 2021 using the EMBASE and MEDLINE databases. Studies that assess the use of calcipotriol and 5-FU to treat actinic keratosis (AK) and cSCC prevention were included.
RESULTS
In total, four studies met the inclusion criteria. Our final analysis included three articles. One clinical trial evaluated the efficacy of calcipotriol plus 5-FU in treating AK. Another clinical trial evaluated the long-term effect of calcipotriol plus 5-FU in prevention of cSCC. A retrospective study evaluated the use of calcipotriol plus 5-FU with cryotherapy.
LIMITATIONS
A limitation of this systematic review is the limited number of clinical trials that examine the combination of 5-FU plus calcipotriol in treating AK. The active control arm (Petroleum jelly plus 5-FU combination) is not equivalent to topical 5-FU monotherapy; hence, no superiority claim can be made vs topical 5-FU in terms of efficacy.
CONCLUSION
Calcipotriol plus 5-FU reduced greater number of AKs in the treated area (25 cm2) when compared to 5-FU plus petroleum jelly, but only 27% of participants had complete clearance on the face at week-8. Calcipotriol plus 5-FU lowered the risk of cSCC on the face and scalp area over a 3-year period. Adequate and well-controlled studies are needed to compare the efficacy of calcipotriol plus 5-FU to 5-FU monotherapy, and other FDA-approved topical drugs such as imiquimod cream and tirbanibulin ointment. J Drugs Dermatol. 2022;21(1):60-65. doi:10.36849/JDD.6632.
Topics: Acetamides; Calcitriol; Carcinoma, Squamous Cell; Fluorouracil; Humans; Keratosis, Actinic; Morpholines; Pyridines; Retrospective Studies; Skin Neoplasms; Treatment Outcome
PubMed: 35005863
DOI: 10.36849/JDD.2022.6632 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241 -
Heart Failure Reviews Mar 2024Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a... (Meta-Analysis)
Meta-Analysis Review
Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.
Topics: Adult; Humans; Middle Aged; Cardiomyopathy, Hypertrophic; Heart; Benzylamines; Myocardium; Uracil
PubMed: 38112937
DOI: 10.1007/s10741-023-10375-6 -
Antiviral Research Jan 2024Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic COVID-19 adult outpatients at high risk for hospitalization and death.
OBJECTIVES
To compare the efficacy and safety of these antivirals based on updated published RCT and real-world data.
STUDY DESIGN
This systematic review followed the preferred reporting items for systematic reviews and meta-analysis framework guidelines. We searched all publications up to January 2023. RRs and 95% CIs for death, hospitalization, and adverse events were calculated.
RESULTS
Six RCTs and seven cohort studies were included, with 1,456,523 participants, of whom 50,979 were treated with antivirals. Remdesivir was associated with the lowest probability of hospitalization and death compared to nirmatrelvir/ritonavir and molnupiravir (P-scores 0.99 and 0.90, respectively, for remdesivir, 0.64 and 0.55, respectively for nirmatrelvir/ritonavir, and 0.26 and 0.49, respectively for molnupiravir). Based on indirect comparisons, remdesivir was associated with a statistically significant decreased risk for hospitalization compared to molnupiravir (RR 0.09; 95% CI 0.02-0.40) and to nirmatrelvir/ritonavir (RR 0.11; 95% CI 0.03-0.73). No statistically significant difference was found between antivirals in the mortality risk reduction and the risk for side effects.
CONCLUSIONS
This is the most comprehensive network meta-analysis integrating RCTs and real-world data. In our indirect comparison, remdesivir was associated with the highest efficacy in preventing hospitalization among high risk symptomatic COVID-19 outpatients, compared to nirmatrelvir/ritonavir and molnupiravir. This finding supports current guidelines, and may have importance when deciding which antiviral to use, together with other important factors.
Topics: Adult; Humans; COVID-19; Network Meta-Analysis; Outpatients; Ritonavir; Antiviral Agents; Hydroxylamines; Cytidine; Nitriles; Lactams; Proline; Leucine
PubMed: 38056602
DOI: 10.1016/j.antiviral.2023.105768 -
European Journal of Clinical... Nov 2020Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients.
METHODS
A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I < 50%, else results were combined using random-effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between-study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.
RESULTS
Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events.
CONCLUSION
Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.
Topics: Adenosine Monophosphate; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; COVID-19; Coronavirus Infections; Europe; Female; Humans; Lopinavir; Male; Pandemics; Pneumonia, Viral; Prognosis; Ritonavir; Survival Analysis; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32810285
DOI: 10.1111/eci.13383