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Journal of Cutaneous Medicine and... 2017Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease resulting from defects in skin barrier and aberrant immune responses. AD significantly affects... (Review)
Review
BACKGROUND
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease resulting from defects in skin barrier and aberrant immune responses. AD significantly affects the quality of life. Not all patients respond to topical therapies, and often systemic therapy is required to control the disease.
OBJECTIVE
To review the treatment options for adult AD patients including those options for patients who do not respond adequately or have contraindications to oral systemic therapy.
METHODS
A working group of clinicians with experience managing AD was convened to review the current literature on treatment options for adult AD patients. This review is based on the best available evidence from a published systematic review and an additional literature search.
RESULTS
Current treatments for AD are reviewed, including options for adult AD patients who do not respond or have contraindications to current systemic therapies. A new approach with targeted therapies is reviewed based on best available evidence.
CONCLUSION
Many AD patients respond satisfactorily to topical or systemic treatments, but for those patients who do not respond or have contraindications, new biologic agents appear to be promising therapies.
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Biological Products; Cyclosporine; Dermatitis, Atopic; Humans; Quality of Life
PubMed: 27635033
DOI: 10.1177/1203475416670364 -
The Cochrane Database of Systematic... Jan 2024Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in adults and currently remains incurable. As the progression-free period shortens... (Review)
Review
BACKGROUND
Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in adults and currently remains incurable. As the progression-free period shortens after each successive treatment, strategies such as maintenance therapy are needed to improve the degree and duration of response to previous therapies. Monoclonal antibodies, immunomodulatory agents, and targeted therapies are among the available options for maintenance therapy. People with CLL who achieve remission after previous therapy may choose to undergo medical observation or maintenance therapy to deepen the response. Even though there is widespread use of therapeutic maintenance agents, the benefits and harms of these treatments are still uncertain.
OBJECTIVES
To assess the effects and safety of maintenance therapy, including anti-CD20 monoclonal antibody, immunomodulatory drug therapy, anti-CD52 monoclonal antibody, Bruton tyrosine kinase inhibitor, and B-cell lymphoma-2 tyrosine kinase inhibitor, for individuals with CLL.
SEARCH METHODS
We conducted a comprehensive literature search for randomised controlled trials (RCTs) with no language or publication status restrictions. We searched CENTRAL, MEDLINE, Embase, and three trials registers in January 2022 together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included RCTs with prospective identification of participants. We excluded cluster-randomised trials, cross-over trial designs, and non-randomised studies. We included studies comparing maintenance therapies with placebo/observation or head-to-head comparisons.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. We assessed risk of bias in the included studies using Cochrane's RoB 1 tool for RCTs. We rated the certainty of evidence for the following outcomes using the GRADE approach: overall survival (OS), health-related quality of life (HRQoL), grade 3 and 4 adverse events (AEs), progression-free survival (PFS), treatment-related mortality (TRM), treatment discontinuation (TD), and all adverse events (AEs).
MAIN RESULTS
We identified 11 RCTs (2393 participants) that met the inclusion criteria, including seven trials comparing anti-CD20 monoclonal antibodies (mAbs) (rituximab or ofatumumab) with observation in 1679 participants; three trials comparing immunomodulatory drug (lenalidomide) with placebo/observation in 693 participants; and one trial comparing anti-CD 52 mAbs (alemtuzumab) with observation in 21 participants. No comparisons of novel small molecular inhibitors were found. The median age of participants was 54.1 to 71.7 years; 59.5% were males. The type of previous induction treatment, severity of disease, and baseline stage varied among the studies. Five trials included early-stage symptomatic patients, and three trials included advanced-stage patients (Rai stage III/IV or Binet stage B/C). Six trials reported a frequent occurrence of cytogenic aberrations at baseline (69.7% to 80.1%). The median follow-up duration was 12.4 to 73 months. The risk of selection bias in the included studies was unclear. We assessed overall risk of performance bias and detection bias as low risk for objective outcomes and high risk for subjective outcomes. Overall risk of attrition bias, reporting bias, and other bias was low. Anti-CD20 monoclonal antibodies (mAbs): rituximab or ofatumumab maintenance versus observation Anti-CD20 mAbs maintenance likely results in little to no difference in OS (hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.73 to 1.20; 1152 participants; 3 studies; moderate-certainty evidence) and likely increases PFS significantly (HR 0.61, 95% CI 0.50 to 0.73; 1255 participants; 5 studies; moderate-certainty evidence) compared to observation alone. Anti-CD20 mAbs may result in: an increase in grade 3/4 AEs (rate ratio 1.34, 95% CI 1.06 to 1.71; 1284 participants; 5 studies; low-certainty evidence); little to no difference in TRM (risk ratio 0.82, 95% CI 0.39 to 1.71; 1189 participants; 4 studies; low-certainty evidence); a slight reduction to no difference in TD (risk ratio 0.93, 95% CI 0.72 to 1.20; 1321 participants; 6 studies; low-certainty evidence); and an increase in all AEs (rate ratio 1.23, 95% CI 1.03 to 1.47; 1321 participants; 6 studies; low-certainty evidence) compared to the observation group. One RCT reported that there may be no difference in HRQoL between the anti-CD20 mAbs (ofatumumab) maintenance and the observation group (mean difference -1.70, 95% CI -8.59 to 5.19; 480 participants; 1 study; low-certainty evidence). Immunomodulatory drug (IMiD): lenalidomide maintenance versus placebo/observation IMiD maintenance therapy likely results in little to no difference in OS (HR 0.91, 95% CI 0.61 to 1.35; 461 participants; 3 studies; moderate-certainty evidence) and likely results in a large increase in PFS (HR 0.37, 95% CI 0.19 to 0.73; 461 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. Regarding harms, IMiD maintenance therapy may result in an increase in grade 3/4 AEs (rate ratio 1.82, 95% CI 1.38 to 2.38; 400 participants; 2 studies; low-certainty evidence) and may result in a slight increase in TRM (risk ratio 1.22, 95% CI 0.35 to 4.29; 458 participants; 3 studies; low-certainty evidence) compared to placebo/observation. The evidence for the effect on TD compared to placebo is very uncertain (risk ratio 0.71, 95% CI 0.47 to 1.05; 400 participants; 2 studies; very low-certainty evidence). IMiD maintenance therapy probably increases all AEs slightly (rate ratio 1.41, 95% CI 1.28 to 1.54; 458 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. No studies assessed HRQoL. Anti-CD52 monoclonal antibodies (mAbs): alemtuzumab maintenance versus observation Maintenance with alemtuzumab may have little to no effect on PFS, but the evidence is very uncertain (HR 0.55, 95% CI 0.32 to 0.95; 21 participants; 1 study; very low-certainty evidence). We did not identify any study reporting the outcomes OS, HRQoL, grade 3/4 AEs, TRM, TD, or all AEs.
AUTHORS' CONCLUSIONS
There is currently moderate- to very low-certainty evidence available regarding the benefits and harms of maintenance therapy in people with CLL. Anti-CD20 mAbs maintenance improved PFS, but also increased grade 3/4 AEs and all AEs. IMiD maintenance had a large effect on PFS, but also increased grade 3/4 AEs. However, none of the above-mentioned maintenance interventions show differences in OS between the maintenance and control groups. The effects of alemtuzumab maintenance are uncertain, coupled with a warning for drug-related infectious toxicity. We found no studies evaluating other novel maintenance interventions, such as B-cell receptor inhibitors, B-cell leukaemia-2/lymphoma-2 inhibitors, or obinutuzumab.
Topics: Adult; Aged; Humans; Middle Aged; Alemtuzumab; Antibodies, Monoclonal; Antineoplastic Agents; Lenalidomide; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Tyrosine Kinase Inhibitors
PubMed: 38174814
DOI: 10.1002/14651858.CD013474.pub2 -
BioDrugs : Clinical Immunotherapeutics,... Aug 2015Monoclonal antibody (mAb)-based orphan drugs have led to advances in the treatment of diseases by selectively targeting molecule functions. However, their high treatment... (Review)
Review
BACKGROUND
Monoclonal antibody (mAb)-based orphan drugs have led to advances in the treatment of diseases by selectively targeting molecule functions. However, their high treatment costs impose a substantial cost burden on patients and society.
OBJECTIVES
The study aimed to systematically review cost-effectiveness evidence of mAb orphan drugs.
METHODS
Ovid MEDLINE(®), EMBASE(®), and PsycINFO(®) were searched in June 2014 and articles were selected if they conducted economic evaluations of the mAb orphan drugs that had received marketing approval in the USA. The quality of the selected studies was assessed using the Quality of Health Economic Studies (QHES) instrument.
RESULTS
We reviewed 16 articles that included 24 economic evaluations of nine mAb orphan drugs. Six of these nine drugs were included in cost-utility analysis studies, whereas three drugs were included in cost-effectiveness analysis studies. Previous cost-utility analysis studies revealed that four mAb orphan drugs (cetuximab, ipilimumab, rituximab, and trastuzumab) were found to be cost effective; one drug (bevacizumab) was not cost effective; and one drug (infliximab) was not consistent across the studies. Prior cost-effectiveness analysis studies which included three mAb orphan drugs (adalimumab, alemtuzumab, and basiliximab) showed that the incremental cost per effectiveness gained for these drugs ranged from $US4669 to $Can52,536 Canadian dollars. The quality of the included studies was good or fair with the exception of one study.
CONCLUSIONS
Some mAb orphan drugs were reported as cost effective under the current decision-making processes. Use of these expensive drugs, however, can raise an equity issue which concerns fairness in access to treatment. The issue of equal access to drugs needs to be considered alongside other societal values in making the final health policy decisions.
Topics: Antibodies, Monoclonal; Cost-Benefit Analysis; Decision Making; Drug Approval; Humans; Orphan Drug Production; Rare Diseases
PubMed: 26263903
DOI: 10.1007/s40259-015-0135-4 -
QJM : Monthly Journal of the... Nov 2021Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19).
AIM
To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients.
DESIGN
A systematic review and meta-analysis.
METHODS
Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses.
RESULTS
Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35-0.93).
CONCLUSION
The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.
Topics: Adult; Antibodies, Monoclonal, Humanized; Humans; Respiration, Artificial; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34010403
DOI: 10.1093/qjmed/hcab142 -
Otolaryngology--head and Neck Surgery :... Jul 2024Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). (Review)
Review
OBJECTIVE
Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP).
DATA SOURCES
PubMed, MEDLINE, Cochrane, and clinical trial registries.
REVIEW METHODS
Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases.
CONCLUSIONS
There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease.
IMPLICATIONS FOR PRACTICE
For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.
Topics: Humans; Sinusitis; Chronic Disease; Rhinitis; Child; Biological Therapy; Nasal Polyps; Omalizumab; Rhinosinusitis; Antibodies, Monoclonal, Humanized
PubMed: 38488239
DOI: 10.1002/ohn.717 -
Autoimmunity Reviews Sep 2021Double-positive patients (DPP) exhibiting anti-glomerular basement membrane (GBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) belong to an entity that is newly... (Review)
Review
INTRODUCTION
Double-positive patients (DPP) exhibiting anti-glomerular basement membrane (GBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) belong to an entity that is newly and poorly described, mainly in short series. We aimed to better characterize the epidemiological features, clinical presentation and therapeutic outcomes of these patients through a systematic review.
METHODS
We performed a systematic review of English-, German-, Spanish- and French-written publications from February 1987 to March 2020 reporting cases of DPP using the following databases: PubMed, Scielo, ScienceDirect, Google Scholar, The Cochrane Library, Open Grey, The Grey Literature Report, Clinicaltrials.gov and International Clinical Trial Registry Platform of the World Health Organization.
RESULTS
In total, 538 DPP were identified from 90 articles. Their clinical presentations were often severe, and the majority exhibited acute kidney failure (91.8%) with a median initial serum creatinine level of 873 μmol/L; 50.7% had alveolar haemorrhage. Other manifestations were present in 30.3% of DPP, mainly ear, nose, throat and articular manifestations. ANCAs were predominantly directed against MPO (n = 377/523; 72.1%) compared to PR3 (n = 107/523; 20.5%), with rare cases of triple positivity (n = 15/538; 2.9%). Although most patients received initial immunosuppressive therapy (n = 285/317; 89.9%), the one-year overall, renal and relapse-free survival rates were 64.8%, 38.7% and 71.1%, respectively.
CONCLUSION
DPP are associated with the characteristics of two eponymous vasculitis types, responsible for a poor overall and renal prognosis. Thus, simultaneous testing of both antibodies and systematic renal biopsy should be recommended in every patient with rapidly progressive glomerulonephritis to recognize this difficult-to-treat and rare disease.
Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Hemorrhage; Humans; Kidney; Prognosis; Vasculitis
PubMed: 34242834
DOI: 10.1016/j.autrev.2021.102885 -
Actas Dermo-sifiliograficas May 2015A great amount of information on systemic and biologic therapies for moderate to severe psoriasis is now available. However, applying the evidence in numerous clinical... (Review)
Review
INTRODUCTION AND OBJECTIVES
A great amount of information on systemic and biologic therapies for moderate to severe psoriasis is now available. However, applying the evidence in numerous clinical scenarios has engendered debate; under these circumstances, the consensus of experts is useful.
MATERIAL AND METHODS
A scientific committee systematically reviewed the literature relevant to 5 clinical scenarios. An online Delphi survey of dermatologists with experience treating moderate to severe psoriasis was then carried out in order to shed light on questions that remained unresolved by the available evidence.
RESULTS
Twenty-three dermatologists responded to the survey and consensus was reached on 37 (56%) of the 66 statements proposed. These results led to consensus on various clinical situations even though firm evidence was lacking. Thus, intermittent therapeutic regimens and strategies for reducing the intensity of treatment are considered appropriate for optimizing biologic treatment and reducing costs. The measurement of drug and antidrug antibody levels should be included routinely when following patients on biologics to treat psoriasis. Concomitant psoriatic arthritis or a history of cardiovascular conditions will influence the choice of biologic; in these situations, an agent with anti-tumor necrosis factor properties will be preferred. Tailored management is important when the patient is pregnant or intends to conceive; drug half-life and disease severity are important factors to take into consideration in these scenarios.
CONCLUSIONS
A combination of systematic review of the literature and structured discussion of expert opinion facilitates decision-making in specific clinical scenarios.
Topics: Age Factors; Aged; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Psoriatic; Biological Therapy; Clinical Decision-Making; Clinical Trials as Topic; Delphi Technique; Dermatology; Drug Substitution; Etanercept; Female; Humans; Immunosuppressive Agents; Male; Multicenter Studies as Topic; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Psoriasis
PubMed: 25595327
DOI: 10.1016/j.ad.2014.11.005 -
Allergy Sep 2021Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune-mediated diseases. However, the diversity of...
BACKGROUND
Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune-mediated diseases. However, the diversity of clinical trials along with the fast pace of publication makes it difficult to determine the level of evidence for the use of a biologic for a given disorder. To address this challenge, we are publishing a series of systematic reviews evaluating the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. In this article, we have assessed the safety and efficacy of belimumab, a fully human IgG1 monoclonal antibody targeting the cytokine B cell-activating factor (BAFF).
OBJECTIVE
To evaluate belimumab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics.
METHODS
The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist guided the reporting of the data. We searched the PubMed database between October 4, 2016, and June 23, 2019, concentrating on immune-mediated disorders.
RESULTS
The literature search identified 583 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 17 articles were finally included in a narrative synthesis.
CONCLUSIONS
Belimumab is both safe and effective for the treatment of systemic lupus erythematosus. Results were further promising for the use of belimumab in patients with rheumatoid arthritis and Sjögren's syndrome. Conversely, results using belimumab in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and myasthenia gravis were rather disappointing.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Humans; Immune System Diseases; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Treatment Outcome
PubMed: 33368349
DOI: 10.1111/all.14704 -
The Cochrane Database of Systematic... Jun 2022Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as potential prophylaxis to... (Review)
Review
BACKGROUND
Monoclonal antibodies (mAbs) are laboratory-produced molecules derived from the B cells of an infected host. They are being investigated as potential prophylaxis to prevent coronavirus disease 2019 (COVID-19).
OBJECTIVES
To assess the effects of SARS-CoV-2-neutralising mAbs, including mAb fragments, to prevent infection with SARS-CoV-2 causing COVID-19; and to maintain the currency of the evidence, using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, and three other databases on 27 April 2022. We checked references, searched citations, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated SARS-CoV-2-neutralising mAbs, including mAb fragments, alone or combined, versus an active comparator, placebo, or no intervention, for pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) of COVID-19. We excluded studies of SARS-CoV-2-neutralising mAbs to treat COVID-19, as these are part of another review.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed search results, extracted data, and assessed risk of bias using Cochrane RoB 2. Prioritised outcomes were infection with SARS-CoV-2, development of clinical COVID-19 symptoms, all-cause mortality, admission to hospital, quality of life, adverse events (AEs), and serious adverse events (SAEs). We rated the certainty of evidence using GRADE.
MAIN RESULTS
We included four RCTs of 9749 participants who were previously uninfected and unvaccinated at baseline. Median age was 42 to 76 years. Around 20% to 77.5% of participants in the PrEP studies and 35% to 100% in the PEP studies had at least one risk factor for severe COVID-19. At baseline, 72.8% to 82.2% were SARS-CoV-2 antibody seronegative. We identified four ongoing studies, and two studies awaiting classification. Pre-exposure prophylaxis Tixagevimab/cilgavimab versus placebo One study evaluated tixagevimab/cilgavimab versus placebo in participants exposed to SARS-CoV-2 wild-type, Alpha, Beta, and Delta variant. About 39.3% of participants were censored for efficacy due to unblinding and 13.8% due to vaccination. Within six months, tixagevimab/cilgavimab probably decreases infection with SARS-CoV-2 (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.29 to 0.70; 4685 participants; moderate-certainty evidence), decreases development of clinical COVID-19 symptoms (RR 0.18, 95% CI 0.09 to 0.35; 5172 participants; high-certainty evidence), and may decrease admission to hospital (RR 0.03, 95% CI 0 to 0.59; 5197 participants; low-certainty evidence). Tixagevimab/cilgavimab may result in little to no difference on mortality within six months, all-grade AEs, and SAEs (low-certainty evidence). Quality of life was not reported. Casirivimab/imdevimab versus placebo One study evaluated casirivimab/imdevimab versus placebo in participants who may have been exposed to SARS-CoV-2 wild-type, Alpha, and Delta variant. About 36.5% of participants opted for SARS-CoV-2 vaccination and had a mean of 66.1 days between last dose of intervention and vaccination. Within six months, casirivimab/imdevimab may decrease infection with SARS-CoV-2 (RR 0.01, 95% CI 0 to 0.14; 825 seronegative participants; low-certainty evidence) and may decrease development of clinical COVID-19 symptoms (RR 0.02, 95% CI 0 to 0.27; 969 participants; low-certainty evidence). We are uncertain whether casirivimab/imdevimab affects mortality regardless of the SARS-CoV-2 antibody serostatus. Casirivimab/imdevimab may increase all-grade AEs slightly (RR 1.14, 95% CI 0.98 to 1.31; 969 participants; low-certainty evidence). The evidence is very uncertain about the effects on grade 3 to 4 AEs and SAEs within six months. Admission to hospital and quality of life were not reported. Postexposure prophylaxis Bamlanivimab versus placebo One study evaluated bamlanivimab versus placebo in participants who may have been exposed to SARS-CoV-2 wild-type. Bamlanivimab probably decreases infection with SARS-CoV-2 versus placebo by day 29 (RR 0.76, 95% CI 0.59 to 0.98; 966 participants; moderate-certainty evidence), may result in little to no difference on all-cause mortality by day 60 (R 0.83, 95% CI 0.25 to 2.70; 966 participants; low-certainty evidence), may increase all-grade AEs by week eight (RR 1.12, 95% CI 0.86 to 1.46; 966 participants; low-certainty evidence), and may increase slightly SAEs (RR 1.46, 95% CI 0.73 to 2.91; 966 participants; low-certainty evidence). Development of clinical COVID-19 symptoms, admission to hospital within 30 days, and quality of life were not reported. Casirivimab/imdevimab versus placebo One study evaluated casirivimab/imdevimab versus placebo in participants who may have been exposed to SARS-CoV-2 wild-type, Alpha, and potentially, but less likely to Delta variant. Within 30 days, casirivimab/imdevimab decreases infection with SARS-CoV-2 (RR 0.34, 95% CI 0.23 to 0.48; 1505 participants; high-certainty evidence), development of clinical COVID-19 symptoms (broad-term definition) (RR 0.19, 95% CI 0.10 to 0.35; 1505 participants; high-certainty evidence), may result in little to no difference on mortality (RR 3.00, 95% CI 0.12 to 73.43; 1505 participants; low-certainty evidence), and may result in little to no difference in admission to hospital. Casirivimab/imdevimab may slightly decrease grade 3 to 4 AEs (RR 0.50, 95% CI 0.24 to 1.02; 2617 participants; low-certainty evidence), decreases all-grade AEs (RR 0.70, 95% CI 0.61 to 0.80; 2617 participants; high-certainty evidence), and may result in little to no difference on SAEs in participants regardless of SARS-CoV-2 antibody serostatus. Quality of life was not reported.
AUTHORS' CONCLUSIONS
For PrEP, there is a decrease in development of clinical COVID-19 symptoms (high certainty), infection with SARS-CoV-2 (moderate certainty), and admission to hospital (low certainty) with tixagevimab/cilgavimab. There is low certainty of a decrease in infection with SARS-CoV-2, and development of clinical COVID-19 symptoms; and a higher rate for all-grade AEs with casirivimab/imdevimab. For PEP, there is moderate certainty of a decrease in infection with SARS-CoV-2 and low certainty for a higher rate for all-grade AEs with bamlanivimab. There is high certainty of a decrease in infection with SARS-CoV-2, development of clinical COVID-19 symptoms, and a higher rate for all-grade AEs with casirivimab/imdevimab. Although there is high-to-moderate certainty evidence for some outcomes, it is insufficient to draw meaningful conclusions. These findings only apply to people unvaccinated against COVID-19. They are only applicable to the variants prevailing during the study and not other variants (e.g. Omicron). In vitro, tixagevimab/cilgavimab is effective against Omicron, but there are no clinical data. Bamlanivimab and casirivimab/imdevimab are ineffective against Omicron in vitro. Further studies are needed and publication of four ongoing studies may resolve the uncertainties.
Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing; Antineoplastic Agents, Immunological; COVID-19; Humans; Middle Aged; SARS-CoV-2
PubMed: 35713300
DOI: 10.1002/14651858.CD014945.pub2 -
The Cochrane Database of Systematic... Jan 2016Lymphomas are the third most common malignancy in childhood. Cure rates are high but have reached a plateau. Therefore new treatment modalities should be developed.... (Review)
Review
BACKGROUND
Lymphomas are the third most common malignancy in childhood. Cure rates are high but have reached a plateau. Therefore new treatment modalities should be developed. Antibody therapy is a successful new treatment option in adult lymphoma. However, none of the therapeutic antibodies available for adults with cancer have been approved for treatment of paediatric lymphoma.
OBJECTIVES
To assess the efficacy of antibody therapy for childhood lymphoma in terms of survival, response and relapse rates, compared with therapy not including antibody treatment. To assess quality of life and the occurrence of adverse effects caused by antibody therapy treatment in children compared with therapy not including antibody treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 10), MEDLINE in PubMed (from 1945 to October 2014), EMBASE in EMBASE.com (from 1980 to October 2014) and reference lists of relevant articles. Furthermore, we searched conference proceedings abstracts of SIOP, ASCO and ASH for studies from 2009 to 2013), and the World Health Organization (WHO) ICTRP portal and ClinicalTrials.gov for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials and controlled clinical trials comparing conventional therapy with antibody therapy in children with lymphoma.
DATA COLLECTION AND ANALYSIS
Two authors independently performed the study selection.
MAIN RESULTS
We found no studies meeting the inclusion criteria of the review.
AUTHORS' CONCLUSIONS
At this moment, it is not possible to draw evidence-based conclusions regarding clinical practice. Phase I and II studies show a positive effect of using antibody therapy in childhood lymphoma. Further research is needed to evaluate and implement antibody therapy for paediatric lymphoma.
Topics: Antibodies, Monoclonal; Child; Humans; Lymphoma
PubMed: 26784573
DOI: 10.1002/14651858.CD011181.pub2