scholarly journals Immunomodulatory therapies for the treatment of SARS-CoV-2 infection: an update of the systematic literature review to inform EULAR points to consider

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001899
Author(s):  
Alessia Alunno ◽  
Aurélie Najm ◽  
Xavier Mariette ◽  
Gabriele De Marco ◽  
Jenny Emmel ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Therapeutic Strategies ◽  
Antibody Responses ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Jak Inhibitors ◽  
Immunomodulatory Agents ◽  
Randomised Controlled ◽  
Immunomodulatory Therapies

ObjectiveTo update the EULAR 2020 systematic literature review (SLR) on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection.MethodsAs part of a EULAR taskforce, a systematic literature search update was conducted from 11 December 2020 to 14 July 2021. Two reviewers independently identified eligible studies and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage of disease. The risk of bias (RoB) was assessed with validated tools.ResultsOf the 26 959 records, 520 articles were eligible for inclusion. Studies were mainly at high or unclear RoB. New randomised controlled trials (RCTs) on tocilizumab clarified its benefit in patients with severe and critical COVID-19, mainly if associated with glucocorticoids. There are emergent data on the usefulness of baricitinib and tofacitinib in severe COVID-19. Other therapeutic strategies such as the use of convalescent plasma and anti-SARS-CoV-2 monoclonal antibodies showed efficacy in subjects not mounting normal anti-SARS-CoV-2 antibody responses.ConclusionThis new SLR confirms that some immunomodulators (tocilizumab and JAK inhibitors) have a role for treating severe and critical COVID-19. Although better evidence is available compared with the previous SLR, the need of RCT with combination therapy (glucocorticoids+anti-cytokines) versus monotherapy with glucocorticoids still remains alongside the need for standardisation of inclusion criteria and outcomes to ultimately improve the care and prognosis of affected people. This SLR informed the 2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19.

scholarly journals Immunomodulatory therapies for SARS-CoV-2 infection: a systematic literature review to inform EULAR points to consider

2021 ◽  
pp. annrheumdis-2020-219725
Author(s):  
Alessia Alunno ◽  
Aurélie Najm ◽  
Xavier Mariette ◽  
Gabriele De Marco ◽  
Jenny Emmel ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Intravenous Immunoglobulins ◽  
Risk Of Bias ◽  
Disease Stage ◽  
Efficacy And Safety ◽  
Immunomodulatory Treatment ◽  
Immunomodulatory Agents ◽  
Randomised Controlled ◽  
Immunomodulatory Therapies

ObjectiveTo summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection.MethodsAs part of a European League Against Rheumatism (EULAR) taskforce, a systematic literature search was conducted from January 2019 to 11 December 2020. Two reviewers independently identified eligible studies according to the Population, Intervention, Comparator and Outcome framework and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage. The risk of bias was assessed with validated tools.ResultsOf the 60 372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs: hydroxychloroquine (n=12), glucocorticoids (n=6), tocilizumab (n=4), convalescent plasma (n=4), interferon beta (n=2), intravenous immunoglobulins (IVIg) (n=2) and n=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa and vilobelimab. Glucocorticoids were able to reduce mortality in specific subsets of patients, while conflicting data were available about tocilizumab. Hydroxychloroquine was not beneficial at any disease stage, one RCT with anakinra was negative, one RCT with baricitinib+remdesivir was positive, and individual trials on some other compounds provided interesting, although preliminary, results.ConclusionAlthough there is emerging evidence about immunomodulatory therapies for the management of COVID-19, conclusive data are scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anticytokine/immunomodulatory treatment are warranted. This systematic literature review informed the initiative to formulate EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory treatment from the rheumatology perspective.

Computer Science Unplugged: A Systematic Literature Review

2021 ◽  
pp. 004723952110188
Author(s):  
Ali Battal ◽  
Gülgün Afacan Adanır ◽  
Yasemin Gülbahar
Keyword(s):  
Literature Review ◽  
Computer Science ◽  
Systematic Literature Review ◽  
Computational Thinking ◽  
Thinking Skills ◽  
Inclusion Criteria ◽  
Relevant Research ◽  
Tangible Programming ◽  
Review Procedure ◽  
Research Studies

The computer science (CS) unplugged approach intends to teach CS concepts and computational thinking skills without employing any digital tools. The current study conducted a systematic literature review to analyze research studies that conducted investigations related to implementations of CS unplugged activities. A systematic review procedure was developed and applied to detect and subsequently review relevant research studies published from 2010 to 2019. It was found that 55 research studies (17 articles + 38 conference proceedings) satisfied the inclusion criteria for the analysis. These research studies were then examined with regard to their demographic characteristics, research methodologies, research results, and main findings. It was found that the unplugged approach was realized and utilized differently among researchers. The majority of the studies used the CS unplugged term when referring to “paper–pencil activities,” “problem solving,” “storytelling,” “games,” “tangible programming,” and even “robotics.”

scholarly journals OP0287 IMMUNOMODULATORY THERAPIES FOR SEVERE FORMS OF COVID-19: A SYSTEMATIC LITERATURE REVIEW TO INFORM EULAR POINTS TO CONSIDER

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 175.1-175
Author(s):  
A. Alunno ◽  
A. Najm ◽  
X. Mariette ◽  
J. Emmel ◽  
L. Mason ◽  
...  
Keyword(s):  
Risk Of Bias ◽  
Respiratory Support ◽  
Disease Stage ◽  
Controlled Trials ◽  
Immunomodulatory Agents ◽  
Randomised Controlled ◽  
Available Information ◽  
Immunomodulatory Therapies ◽  
Global Health Problem

Background:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, a deleterious aberrant non-effective host immune response plays an important role especially in severe forms of COVID-19. There is intense investigation to explore the utility of immunomodulatory drugs commonly used in the Rheumatology arena as agents that may mitigate against COVID-19 to improve disease prognosis. Rheumatologists are used to the utilization of these immune targeted therapies.Objectives:To summarize the available information on the use of immunomodulatory agents in severe COVID-19.Methods:As part of a EULAR taskforce, a systematic literature search was conducted from January 2019 up to December 11, 2020. Two reviewers independently identified eligible studies according to the PICO framework P (population): patients with SARS-CoV-2 infection; I (intervention): any immunomodulator agent/strategy; C (comparator): any comparator; O (outcome) any clinical outcome including but not limited to mortality, admission to intensive care unit and clinical improvement. Data on efficacy and safety of immunomodulatory agents utilized therapeutically in SARS-CoV-2 infection at any stage were extracted. The risk of bias was assessed using validated tools.Results:Of 60372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs: hydroxychloroquine (N=12), glucocorticoids (N=6), tocilizumab (N= 4), convalescent plasma (N=4), interferon beta (N=2), IVIg (N=2) and N=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa, and vilobelimab. For glucocorticoids, dexamethasone reduced mortality only in patients requiring respiratory support; while methylprednisolone reduced mortality in patients aged 60 years or over. Data from RCTs on tocilizumab are conflicting and definite conclusions cannot be drawn at this point in time, but recent studies suggest possible benefit in patients requiring respiratory support. Hydroxychloroquine was not beneficial at any disease stage, one RCT with anakinra was negative, one RCT with baricitinib+remdesivir was positive, and individual trials testing some other compounds provided interesting, albeit preliminary, results.Conclusion:Although there is emerging evidence about immunomodulatory therapies for the management of COVID-19, conclusive data is scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anti-cytokine/immunomodulatory treatment are warranted. This SLR informed the initiative to formulate EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19.Figure 1.Forest plots showing the risk ratio (RR) and 95% confidence interval for mortality in randomized controlled trials divided by intervention. The latest follow-up available is reported in the timing column.Disclosure of Interests:None declared

scholarly journals Understanding Preferences for Coastal Climate Change Adaptation: A Systematic Literature Review

2021 ◽  
Vol 13 (15) ◽  
pp. 8594
Author(s):  
Angela Mallette ◽  
Timothy F. Smith ◽  
Carmen Elrick-Barr ◽  
Jessica Blythe ◽  
Ryan Plummer
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Place Attachment ◽  
Private Property ◽  
Public Support ◽  
Inclusion Criteria ◽  
Policy Makers ◽  
Coastal Adaptation ◽  
Significant Research ◽  
Response Policy

Lack of public support for coastal adaptation can present significant barriers for implementation. In response, policy makers and academics are seeking strategies to build public support for coastal adaptation, which requires a deeper understanding of peoples’ preferences for coastal adaptation and what motives those preferences. Here, we conduct a systematic literature review to understand preferences for coastal adaptation options and the factors influencing these preferences. Ninety peer-reviewed publications meet the inclusion criteria. The findings revealed that hard protection options were often the most frequently preferred, likely due to a desire to maintain current shoreline, for the protection of recreational spaces and private property, and a perceived effectiveness of hard protection options. Soft protection, including nature-based approaches, accommodation, and no action were the next most preferred options. Finally, retreat options were the least preferred, often due to strong place attachment. We identify twenty-eight factors that could influence preferences, with risk perception, place attachment, and financial considerations occurring most frequently in the literature. In the conclusion, we outline the most significant research gaps identified from our analysis and discuss the implication for adaptation research and practice.

scholarly journals SAT0052 THERAPEUTIC STRATEGIES IN DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: PRELIMINARY RESULTS OF A SYSTEMATIC LITERATURE REVIEW INFORMING THE 2020 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 957-957
Author(s):  
N. M. T. Roodenrijs ◽  
A. Hamar ◽  
M. Kedves ◽  
G. Nagy ◽  
J. M. Van Laar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Therapeutic Strategies ◽  
Eular Recommendations ◽  
Management Interventions ◽  
Fatigue Exercise ◽  
Factor Inhibitor ◽  
Management Recommendations ◽  
Sat 1

Background:Rheumatoid arthritis (RA) patients treated according to European League Against Rheumatism (EULAR) recommendations failing ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with a different mode of action who still have complaints which may be suggestive of active disease may be defined as suffering from ‘difficult-to-treat RA’. Management recommendations for RA focus predominantly on the earlier phases of the disease and specific recommendations for difficult-to-treat RA patients are currently lacking.1Objectives:To systematically summarise evidence in the literature on pharmacological and non-pharmacological therapeutic strategies for difficult-to-treat RA patients, informing the 2020 EULAR recommendations for the management of difficult-to-treat RA.Methods:A systematic literature review (SLR) was performed: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.Results:Thirty articles were selected for therapeutic strategies in patients with limited DMARD options due to contraindications, 73 for patients in whom previous b/tsDMARDs were not effective (‘true refractory RA’), and 51 for patients with predominantly non-inflammatory complaints. For patients with limited DMARD options, limited evidence was found on effective DMARD options for patients with concomitant obesity, and on safe DMARD options for patients with concomitant hepatitis B and C. In patients who failed ≥2 bDMARDs, tocilizumab, tofacitinib, baricitinib, upadacitinib and filgotinib were found to be more effective than placebo, but evidence was insufficient to prioritise. In patients who failed ≥1 bDMARD, there was a tendency of non-tumour necrosis factor inhibitor (TNFi) bDMARDs to be more effective than TNFi (Figure 1). Generally, b/tsDMARDs become less effective when patients failed more bDMARDs, this tendency was not clear for upadacitinib and filgotinib (Figure 2). In patients with predominantly non-inflammatory complaints (mainly function, pain and fatigue), exercise, education, psychological and self-management interventions were found to be of additional benefit.Conclusion:This SLR underscores the scarcity of evidence on the optimal treatment of difficult-to-treat RA patients. As difficult-to-treat RA is a newly defined disease state, all evidence is to an extent indirect. Several b/tsDMARDs were found to be effective in patients who failed ≥2 bDMARDs and generally effectiveness decreased with a higher number of failed bDMARDs. Additionally, a beneficial effect of non-pharmacological interventions was found on non-inflammatory complaints.References:[1] Smolen JSet al. Ann Rheum Dis2020. Epub ahead of print.Disclosure of Interests:Nadia M. T. Roodenrijs: None declared, Attila Hamar: None declared, Melinda Kedves: None declared, György Nagy: None declared, Jacob M. van Laar Grant/research support from: MSD, Genentech, Consultant of: MSD, Roche, Pfizer, Eli Lilly, BMS, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Paco Welsing: None declared

scholarly journals Lantox—The Chinese Botulinum Toxin Drug—Complete English Bibliography and Comprehensive Formalised Literature Review

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 370
Author(s):  
Dirk Dressler ◽  
Lizhen Pan ◽  
Junhui Su ◽  
Fei Teng ◽  
Lingjing Jin
Keyword(s):  
Literature Review ◽  
Observational Studies ◽  
Similar Efficacy ◽  
Conversion Ratio ◽  
Brand Names ◽  
Efficacy And Safety ◽  
Paper Citation ◽  
Safety Features ◽  
Randomised Controlled ◽  
Nose And Throat

In 1997, lanbotulinumtoxinA (LAN) was introduced in China. It is now available in Asia, Latin America and Eastern Europe under various brand names including Hengli®, Lantox®, Prosigne®, Lanzox®, Redux®, Liftox®, HBTX-A and CBTX-A. The literature on LAN is mostly published in Chinese language, restricting its international accessibility. We, therefore, wanted to generate a complete English bibliography of all LAN publications and then use it for a comprehensive formalised literature review. Altogether, 379 LAN publications (322 in Chinese and 57 in English) were retrieved from PubMed and Science and Technology Paper Citation Database. Indications covered are motor (257), glandular (16), pain (32) and aesthetics (48). Topics are neurological (250), aesthetic (48), paediatric (38), ophthalmological (18), urological (9), methodological (6), gastroenterological (5), ear, nose and throat (4) and surgical (1). Seventy-one publications are randomised controlled trials, forty-one publications are interventional studies and observational studies, fifteen publications are case studies, eighteen publications are reviews, and two publications are guidelines. LAN publications cover all relevant topics of BT therapy throughout a period of more than 20 years. This constitutes a publication basis resembling those of other BT drugs. None of the LAN publications presents data contradictory to those generated with other BT type-A drugs. LAN seems to have a similar efficacy and safety features when compared to onabotulinumtoxinA using a 1:1 LAN– onabotulinumtoxinA conversion ratio. Large controlled multicentre studies will become necessary for LAN’s registrations in Europe and North America.

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