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Best Practice & Research. Clinical... Mar 2021Several immunosuppressive therapies have been investigated as potential treatments for patients with severe and critical coronavirus disease 2019 (COVID-19). Notable... (Review)
Review
Several immunosuppressive therapies have been investigated as potential treatments for patients with severe and critical coronavirus disease 2019 (COVID-19). Notable examples include corticosteroids, interleukin 6 (IL-6), interleukin 1 (IL-1), Janus kinase (JAK), and tumor necrosis factor alpha (TNF-α) inhibitors. The aim of this narrative review is to analyze the mechanistic rationale and available evidence for these selected anti-rheumatic drugs for the treatment of COVID-19. Currently, only corticosteroids have consistently proven to be effective in decreasing mortality and are recommended in clinical guidelines for the treatment of severe and critical COVID-19. Multiple randomized controlled trials (RCTs) are ongoing to determine the role of other immunosuppressants.
Topics: Antirheumatic Agents; COVID-19; Humans; Immunosuppressive Agents; Rheumatic Diseases; SARS-CoV-2
PubMed: 33526326
DOI: 10.1016/j.berh.2021.101659 -
Current HIV/AIDS Reports Dec 2019The population of HIV-exposed uninfected (HEU) children is expanding rapidly, and over one million HEU infants are born each year globally. Several recent studies have... (Review)
Review
PURPOSE OF REVIEW
The population of HIV-exposed uninfected (HEU) children is expanding rapidly, and over one million HEU infants are born each year globally. Several recent studies have reported that HEU children, particularly in low- and middle-income countries, are at risk of poor outcomes, including impaired growth and neurodevelopment. However, the reasons for poor clinical outcomes amongst HEU children remain unclear.
RECENT FINDINGS
We summarise the findings from recent large studies that have characterised growth and neurodevelopment in HEU children, identified risk factors and explored underlying mechanistic pathways. We propose a conceptual framework to explain how exposure to HIV and antiretroviral therapy (ART) may lead to adverse growth and neurodevelopment in uninfected children, and review the available evidence and research gaps. We propose that HEU children are affected both indirectly, through the augmentation of universal risk factors underlying poor growth and neurodevelopment, and directly through HIV/ART-specific pathways, which ultimately may converge through a series of common pathogenic mechanisms. In the era of universal ART, a better understanding of these pathways is crucial to inform future prevention and intervention strategies.
Topics: Antirheumatic Agents; Child; Child Development; Female; HIV Infections; Humans; Infant; Male; Maternal Exposure; Pregnancy; Pregnancy Complications, Infectious
PubMed: 31732866
DOI: 10.1007/s11904-019-00459-0 -
Rheumatology (Oxford, England) Oct 2020There have been major advances in the management of axial spondyloarthritis (axSpA) with the introduction of effective biologic agents targeting TNF and IL-17A.... (Review)
Review
There have been major advances in the management of axial spondyloarthritis (axSpA) with the introduction of effective biologic agents targeting TNF and IL-17A. Clinicians now have more choice but, despite treatment recommendations, are still faced with significant uncertainty when deciding on the optimal treatment strategy for an individual patient in clinical practice. Management of axSpA typically requires both non-pharmacological and pharmacological interventions. NSAIDs remain the first line drug therapies for axSpA with proven efficacy for symptomatic management but uncertainty remains regarding their optimal long-term use relating to radiographic progression and safety in axSpA. To-date there are no head-to-head trials of biologics in axSpA. Clinicians need to consider other factors, including extra-articular manifestations, comorbidities, safety and radiographic progression when deciding on which biologic to recommend for an individual patient. This article will explore the evidence relating to these factors and highlight areas of unmet need.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Cytokines; Disease Progression; Humans; Janus Kinase Inhibitors; Spondylarthritis
PubMed: 33053192
DOI: 10.1093/rheumatology/keaa435 -
Frontiers in Immunology 2023Giant cell arteritis and Takayasu arteritis are two types of primary large-vessel vasculitis (LVV). Although glucocorticoids (GC) are the standard treatment for LVV, the... (Review)
Review
Giant cell arteritis and Takayasu arteritis are two types of primary large-vessel vasculitis (LVV). Although glucocorticoids (GC) are the standard treatment for LVV, the disease relapse rates are high. Recent clinical trials on biological disease-modifying anti-rheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors have demonstrated their efficacy in reducing LVV relapse rates and GC dosages. However, the control of residual inflammation and degenerative alterations in the vessel wall remains an outstanding requirement in the clinical management of LVV. The analysis of immune cell phenotypes in patients with LVV may predict their response to treatment with bDMARDs and JAK inhibitors and guide their optimal use. In this mini-review, we focused on molecular markers, including the immune cell proportions and gene expression, in patients with LVV and in mouse models of LVV treated with bDMARDs and JAK inhibitors.
Topics: Animals; Mice; Janus Kinase Inhibitors; Antirheumatic Agents; Giant Cell Arteritis; Takayasu Arteritis; Recurrence
PubMed: 37197652
DOI: 10.3389/fimmu.2023.1197342 -
Clinical Drug Investigation Aug 2021Filgotinib (Jyseleca), an oral Janus kinase (JAK) inhibitor, is approved as monotherapy or in combination with methotrexate to treat moderate to severe active rheumatoid... (Review)
Review
Filgotinib (Jyseleca), an oral Janus kinase (JAK) inhibitor, is approved as monotherapy or in combination with methotrexate to treat moderate to severe active rheumatoid arthritis (RA) in adults who have an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). In phase 3 trials, once-daily filgotinib was generally well tolerated and associated with an improvement in RA signs and symptoms as well as physical function in patients with an inadequate response to ongoing methotrexate, an inadequate response to ongoing conventional synthetic DMARDs plus an inadequate response or intolerance to prior biologic DMARDs, or limited or no prior exposure to methotrexate. In addition, filgotinib was noninferior to adalimumab in terms of low disease activity response rate (DAS28-CRP ≤ 3.2) in patients with an inadequate response to methotrexate. Filgotinib also appeared to inhibit the radiographic progression of joint damage and led to low disease activity or disease remission (DAS28-CRP < 2.6). Filgotinib showed sustained efficacy, and the safety profile of filgotinib longer term was similar to that in the phase 2 and 3 trials.
Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Humans; Pyridines; Triazoles
PubMed: 34304373
DOI: 10.1007/s40261-021-01055-0 -
Chinese Medical Journal Nov 2022
Topics: Humans; Etanercept; Antirheumatic Agents; Spondylarthritis; Axial Spondyloarthritis; Spondylitis, Ankylosing
PubMed: 35261349
DOI: 10.1097/CM9.0000000000001986 -
Clinical and Experimental Rheumatology 2020Rheumatoid arthritis (RA) management is driven by evidence, and new 2019 EULAR recommendations help in refining the relevant place of different disease-modifying... (Review)
Review
Rheumatoid arthritis (RA) management is driven by evidence, and new 2019 EULAR recommendations help in refining the relevant place of different disease-modifying anti-rheumatic drugs (DMARDs) in treatment schedules. At present, new drugs are in phase of development, mainly Janus Kinase inhibitors (JAKis), however, specific treatment strategies seem to count more than individual DMARDs in terms of treatment responses, given the substantial lack of head-to-head comparisons between specific biological (b) and targeted synthetic (ts)DMARDs, and with the general perception of a similar efficacy profile across drugs. In this setting, when reliable biomarkers able to predict treatment responses are lacking, treatment decisions are mainly driven by specific clinical or individual factors, given the recognised role of comorbidities, treatment-specific side effects, patients’ preferences, and costs on drug choice. In this narrative review, the authors give their specific point of view on the management of RA, based on a critical revision of the literature published in 2019, focusing on relevant novelties and future research directions.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Janus Kinase Inhibitors; Patient Preference
PubMed: 32213264
DOI: 10.55563/clinexprheumatol/n6zc67 -
The Journal of Rheumatology Feb 2023This literature review aimed to identify the most efficacious current interventions for dactylitis and provide up-to-date scientific evidence to support the 2021 Group... (Review)
Review
OBJECTIVE
This literature review aimed to identify the most efficacious current interventions for dactylitis and provide up-to-date scientific evidence to support the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommendations on the management of psoriatic arthritis.
METHODS
Original articles published from 2013 to 2020, registered in MEDLINE, Embase, and Cochrane Library, describing interventional trials and reporting dactylitis-related outcomes were included. The 20 members of the GRAPPA dactylitis group were divided into 9 subgroups according to treatment, and members of each group independently extracted data from articles/abstracts corresponding to their group by using a standardized data extraction form.
RESULTS
Forty-nine publications were analyzed, representing 40 randomized clinical trials (RCTs) and including 16,752 patients. Dactylitis was assessed as a secondary outcome in 97.5% of these trials and more than 40% of RCTs did not employ a specific dactylitis measure or instrument.
CONCLUSION
The emergence of agents with novel mechanisms of action in recent years, such as interleukin 17 (IL-17), IL-12/23, IL-23, and Janus kinase inhibitors, has significantly expanded the available treatment options for dactylitis. This article points out the lack of consensus regarding dactylitis assessment and the paucity of data concerning the effect of local steroid injections, nonsteroidal antiinflammatory drugs, and conventional disease-modifying antirheumatic drugs. Clinical trials evaluating the effect of these traditional and low-cost medications used to treat dactylitis should be encouraged.
Topics: Humans; Arthritis, Psoriatic; Psoriasis; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Interleukin-12
PubMed: 36319013
DOI: 10.3899/jrheum.220311 -
Biomedicine & Pharmacotherapy =... Feb 2020Iguratimod (IGU) is a novel small-molecule anti-rheumatic drug with remarkable effectiveness and good safety for the treatment of active rheumatoid arthritis. Its... (Review)
Review
Iguratimod (IGU) is a novel small-molecule anti-rheumatic drug with remarkable effectiveness and good safety for the treatment of active rheumatoid arthritis. Its mechanism of action is related to its ability to act simultaneously on T and B lymphocytes. IGU can effectively inhibit expression of various inflammatory factors, inhibit B cells from producing immunoglobulins and autoantibodies, downregulate T-cell-mediated cellular immunity, accelerate bone formation, and exert some activity against anti-pulmonary fibrosis. In recent years, IGU has been gradually applied to the treatment of a variety of rheumatic diseases, such as Sjögren's syndrome, ankylosing spondylitis and systemic lupus erythematosus. This article reviews the mechanism of action and clinical research status of IGU, and provides reference for future research on its mechanism of action and clinical application.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Chromones; Humans; Sulfonamides
PubMed: 31918275
DOI: 10.1016/j.biopha.2019.109704 -
The Journal of Rheumatology May 2024To conduct a systematic review of the effectiveness and safety of pharmacological treatments for adult-onset Still disease (AOSD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review of the effectiveness and safety of pharmacological treatments for adult-onset Still disease (AOSD).
METHODS
Six databases, 2 trial registries, and conference abstracts were searched from January 2012 to February 2023 for studies of pharmacological interventions in people with AOSD. Outcomes were rates of remission and response, discontinuation of concurrent treatments, complications of AOSD, and treatment-related adverse events. Risk of bias was assessed with the Cochrane risk of bias tool and the Joanna Briggs Institute tool for case series.
RESULTS
Forty-four studies evaluated treatments, including nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids (CS), conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biologic DMARDs (bDMARDs). For bDMARDs, tocilizumab (TCZ), anakinra (ANK), and canakinumab (CNK) had the most available data. Although 3 randomized controlled trials did not show statistically significant benefits of bDMARDs, metaanalyses showed high rates of complete remission and CS discontinuation. Complete remission was 80% (95% CI 59-92%, 36%), 73% (95% CI 58-84%, 66%), and 77% (95% CI 29-97%, 82%) and CS discontinuation was 57% (95% CI 29-81%, 66%), 47% (95% CI 18-78%, 79%), and 34% (95% CI 6-81%, 59%), respectively, for TCZ, ANK, and CNK. Studies with a higher proportion of patients previously treated with bDMARDs showed a trend toward lower rates of CS discontinuation ( = 0.05). The analyses had high clinical heterogeneity, largely because treatments were prescribed as different lines of therapy.
CONCLUSION
Evidence supports TCZ, ANK, and CNK therapy for AOSD. However, the magnitude of effect and comparative effectiveness of treatments is uncertain.
Topics: Adult; Humans; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Biological Products; Interleukin 1 Receptor Antagonist Protein; Remission Induction; Still's Disease, Adult-Onset; Treatment Outcome
PubMed: 38302170
DOI: 10.3899/jrheum.2023-0995