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Arthritis & Rheumatology (Hoboken, N.J.) Aug 2021To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN).
OBJECTIVE
To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN).
METHODS
Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel.
RESULTS
We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted.
CONCLUSION
These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.
Topics: Antirheumatic Agents; Cyclophosphamide; Disease Management; Evidence-Based Medicine; Glucocorticoids; Humans; Polyarteritis Nodosa; Rheumatology; United States
PubMed: 34235883
DOI: 10.1002/art.41776 -
Arthritis Care & Research Aug 2021To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel...
OBJECTIVE
To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis.
METHODS
Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel.
RESULTS
We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions.
CONCLUSION
These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.
Topics: Clinical Decision-Making; Consensus; Decision Support Techniques; Drug Therapy, Combination; Evidence-Based Medicine; Giant Cell Arteritis; Glucocorticoids; Humans; Immunosuppressive Agents; Rheumatology; Takayasu Arteritis; Treatment Outcome
PubMed: 34235871
DOI: 10.1002/acr.24632 -
Current Rheumatology Reports Jul 2021We lack evidence-based data for the treatment of childhood-onset Takayasu arteritis (c-TA) since it is a rare disease in children. In this systematic literature review,... (Review)
Review
PURPOSE OF REVIEW
We lack evidence-based data for the treatment of childhood-onset Takayasu arteritis (c-TA) since it is a rare disease in children. In this systematic literature review, we aimed to evaluate the treatment choices in c-TA patients and integrate our experience for the treatment of our patients in the recent years/in the biologic era.
RECENT FINDINGS
We reviewed 24 articles addressing treatments of 413 c-TA patients. Steroids were given to 352 patients (85.2%) as the main immunosuppressive therapy. Other immunosuppressive agents included methotrexate (37.3%), cyclophosphamide (24.5%), azathioprine (16.9%), and mycophenolate mofetil (7.9%). Besides, various biological agents were used, including tumor necrosis factor-alpha inhibitors in 70 of 107 c-TA patients (65.4%) and interleukin-6 inhibitors in 33 of them (30.8%). Biologics are increasingly used in our center as well. Even in severe patients, CYC is switched to either anti-TNF or antiIL6 once disease control is achieved. Recently, in addition to conventional immunosuppressants, biologics are increasingly used in c-TA. We have revised our treatment protocol to start with 1-3 doses of high-dose steroids and CYC, in a child with TA with types III-V involvement and high acute phase reactants; once clinical features subside and CRP normalizes, biologics should be started to replace CYC while decreasing the steroid dose.
Topics: Azathioprine; Child; Humans; Immunosuppressive Agents; Takayasu Arteritis; Treatment Outcome; Tumor Necrosis Factor Inhibitors
PubMed: 34218346
DOI: 10.1007/s11926-021-01032-8 -
Archives of Medical Sciences.... 2021Takayasu arteritis (TA) is a chronic vasculitis associated with an increased cardiovascular risk. The measurement of pulse wave velocity (PWV), carotid artery...
INTRODUCTION
Takayasu arteritis (TA) is a chronic vasculitis associated with an increased cardiovascular risk. The measurement of pulse wave velocity (PWV), carotid artery intima-media thickness (CIMT) and flow-mediated dilatation (FMD) are generally used for evaluating the cardiovascular risk. The application of these measurements to TA patients remains undetermined.
MATERIAL AND METHODS
Clinical studies that reported the PWV, CIMT and FMD levels in TA patients, which were published prior to 2021, were summarized using PubMed.
RESULTS
Fifteen studies were eligible. Overall, in TA patients, the PWV and CIMT levels were significantly higher and the FMD levels were significantly lower compared to controls. Part of the studies showed that the disease activity of TA was significantly associated with the PWV, CIMT or FMD levels.
CONCLUSIONS
The PWV, CIMT and FMD measurements could be useful for evaluating the cardiovascular risk in TA patients. Further studies to determine the proper use of these measurements are warranted.
PubMed: 34027216
DOI: 10.5114/amsad.2021.105390 -
Rheumatology (Oxford, England) Sep 2021Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis of the middle-size vessels, confined to the skin. We conducted a systematic review in order to identify...
OBJECTIVE
Cutaneous polyarteritis nodosa (CPAN) is a necrotizing vasculitis of the middle-size vessels, confined to the skin. We conducted a systematic review in order to identify studies evaluating the different treatment modalities used in CPAN.
METHODS
This systematic review was conducted according to PRISMA guidelines, registered in PROSPERO: CRD42020222195. PubMed/Medline databases were searched from inception to December of 2020 using the terms: (Polyarteritis nodosa[Title/Abstract]) AND ((therapy[Title/Abstract]) OR (management[Title/Abstract]) OR (treatment[Title/Abstract]))' and 'Cutaneous arteritis [Title/Abstract]'. Articles evaluating pertaining to the management of CPAN in adults were eligible for inclusion.
RESULTS
A total of seven eligible case series with 325 unique patients were included. No study included a control population. In general, systemic corticosteroids were widely used as induction treatment. Immunosuppressive agents combined with corticosteroids were AZA, hydroxychloroquine, sulfasalazine, sulphapyridine, CYC, MTX, mycophenolate, tacrolimus, rituxima and thalidomide. Other agents utilized in the studies were dapsone, colchicine, non-steroid anti-inflammatory drugs, salicylates, warfarin and clopidogrel. In some studies, the presence of ulcerations was associated with an increased risk of relapse.
CONCLUSION
The evidence available regarding the management of patients with CPAN is limited at best. Further studies are needed in order to evaluate the effect of treatment on disease remission, relapses and mortality.
Topics: Drug Therapy, Combination; Humans; Polyarteritis Nodosa
PubMed: 33944902
DOI: 10.1093/rheumatology/keab402 -
Rheumatology (Oxford, England) Nov 2021Takayasu arteritis (TAK) is a rare autoimmune rheumatic disease causing large-vessel vasculitis. Onset is typically between the ages of 20 and 30 years. It is associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Takayasu arteritis (TAK) is a rare autoimmune rheumatic disease causing large-vessel vasculitis. Onset is typically between the ages of 20 and 30 years. It is associated with substantial morbidity and mortality, notably due to its effects on the cardiovascular system. It has a poorly understood global epidemiology. Our objective was to systematically review the available evidence in order to calculate the incidence rate of TAK.
METHODS
Three databases (MEDLINE, PubMed and Embase) were searched in November 2019 and the results were screened by two reviewers. A random effects meta-analysis was then conducted in R to calculate the overall incidence rate. Heterogeneity was assessed using I2. The quality of the studies was assessed using an adapted Newcastle-Ottawa scale. Further subgroup analyses were performed by quality, sex, research setting and geographical location. Publication bias was assessed using a Begg's funnel plot.
RESULTS
The incidence rate for TAK was 1.11 per million person-years (95% CI 0.70-1.76). The heterogeneity in the data was extremely high in all analyses, which suggests that there was considerable variation in incidence rates across the different populations studied. TAK was found to be more common in women (incidence rate 2.01 per million person-years, 95% CI 1.39-2.90).
CONCLUSIONS
TAK is an extremely rare disease. It affects women more commonly than men. There is considerable variation in the incidence rate between populations. We suggest that future research should focus on discrete populations in order to better identify genetic and environmental risk factors.
Topics: Global Health; Humans; Incidence; Takayasu Arteritis
PubMed: 33944899
DOI: 10.1093/rheumatology/keab406 -
European Journal of Nuclear Medicine... Nov 2021Monitoring disease activity in patients with large vessel vasculitis (LVV) can be challenging. [18F]FDG-PET/CT is increasingly used to evaluate treatment response in... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Monitoring disease activity in patients with large vessel vasculitis (LVV) can be challenging. [18F]FDG-PET/CT is increasingly used to evaluate treatment response in LVV. In this systematic review and meta-analysis, we aimed to summarize the current evidence on the value of [18F]FDG-PET/CT for treatment monitoring in LVV.
METHODS
PubMed/MEDLINE and the Cochrane library database were searched from inception through October 21, 2020. Studies containing patients with LVV (i.e. giant cell arteritis, Takayasu arteritis and isolated aortitis) that received treatment and underwent [18F]FDG-PET/CT were included. Screening, full-text review and data extraction were performed by 2 investigators. The risk of bias was examined with the QUADAS-2 tool. Meta-analysis of proportions and diagnostic test accuracy was performed by a random-effects model and bivariate model, respectively.
RESULTS
Twenty-one studies were included in the systematic review, of which 8 studies were eligible for meta-analysis. Arterial [18F]FDG uptake decreased upon clinical remission in longitudinal studies. High heterogeneity (I statistic 94%) precluded meta-analysis of the proportion of patients in which the scan normalized during clinical remission. Meta-analysis of cross-sectional studies indicated that [18F]FDG-PET/CT may detect relapsing/refractory disease with a sensitivity of 77% (95%CI 57-90%) and specificity of 71% (95%CI 47-87%). Substantial heterogeneity was observed among the cross-sectional studies. Both variation in clinical aspects and imaging procedures contributed to the heterogeneity.
CONCLUSION
Treatment of LVV leads to reduction of arterial [18F]FDG uptake during clinical remission. [18F]FDG-PET/CT has moderate diagnostic accuracy for detecting active LVV. [18F]FDG-PET/CT may aid treatment monitoring in LVV, but its findings should be interpreted in the context of the clinical suspicion of disease activity. This study underlines the relevance of published procedural recommendations for the use of [18F]FDG-PET/CT in LVV.
Topics: Arteritis; Cross-Sectional Studies; Fluorodeoxyglucose F18; Humans; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 33942141
DOI: 10.1007/s00259-021-05362-8 -
Clinical Rheumatology Nov 2021The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science,... (Meta-Analysis)
Meta-Analysis Review
The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science, Pubmed Central, clinical trial databases and recent international rheumatology conferences for interventional and observational studies reporting the effectiveness of DMARDs in TAK identified four randomized controlled trials (RCTs, with another longer-term follow-up of one RCT) and 63 observational studies. The identified trials had some concern or high risk of bias. Most observational studies were downgraded on the Newcastle-Ottawa scale due to lack of appropriate comparator groups. Studies used heterogenous outcomes of clinical responses, angiographic stabilization, normalization of inflammatory markers, reduction in vascular uptake on positron emission tomography, reduction in prednisolone doses and relapses. Tocilizumab showed benefit in a RCT compared to placebo in a secondary per-protocol analysis but not the primary intention-to-treat analysis. Abatacept failed to demonstrate benefit compared to placebo for preventing relapses in another RCT. Pooled data from uncontrolled observational studies demonstrated beneficial clinical responses and angiographic stabilization in nearly 80% patients treated with tumour necrosis factor alpha inhibitors, tocilizumab or leflunomide. Certainty of evidence for outcomes from RCTs ranged from moderate to very low and was low to very low for all observational studies. There is a paucity of high-quality evidence to guide the pharmacotherapy of TAK. Future observational studies should attempt to include appropriate comparator arms. Multicentric, adequately powered RCTs assessing both clinical and angiographic responses are necessary in TAK.
Topics: Abatacept; Antibodies, Monoclonal; Antirheumatic Agents; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Takayasu Arteritis
PubMed: 33932173
DOI: 10.1007/s10067-021-05743-2 -
Seminars in Arthritis and Rheumatism Jun 2021Diagnosis of childhood polyarteritis nodosa (PAN) has become challenging after the definition of deficiency of adenosine deaminase 2 (DADA2). We aimed to define the...
BACKGROUND
Diagnosis of childhood polyarteritis nodosa (PAN) has become challenging after the definition of deficiency of adenosine deaminase 2 (DADA2). We aimed to define the differential features of pediatric PAN and DADA2 patients in our center and in the literature.
METHODS
The charts of pediatric PAN and DADA2 patients followed at the Pediatric Rheumatology Unit of Hacettepe University between 2010-2020 were analyzed. A systematic literature review was conducted for articles regarding pediatric PAN or DADA2.
RESULTS
Thirty-four pediatric PAN and 18 pediatric DADA2 patients were included. The age at onset was younger, parental consanguinity, livedo reticularis, neurologic involvement (especially strokes), lymphopenia, and hypogammaglobulinemia were more frequent, while thrombocytosis and panniculitis were less frequent in DADA2 patients. The primary treatment was anti-tumor necrosis factor (anti-TNF) in DADA2. For induction treatment, all systemic PAN patients received corticosteroids, and cyclophosphamide (n=11) or mycophenolate mofetil (MMF) (n = 3). Cyclophosphamide was replaced with MMF in nine once remission was confirmed with PVAS. In the literature, 28 articles describing 613 pediatric PAN patients and 26 articles describing 207 pediatric DADA2 patients were identified. Neurologic, gastrointestinal, and cardiac involvements were more frequent in DADA2, while constitutional symptoms and testis involvement were more common in PAN.
CONCLUSION
In a child with PAN-like phenotype, DADA2 should be considered in the presence of young age at disease onset, parental consanguinity, strokes, lymphopenia, and lack of thrombocytosis during active disease. Anti-TNF treatment is indicated for vasculitic DADA2. Cyclophosphamide could be switched to MMF when remission is confirmed with PVAS in severe PAN.
Topics: Adenosine Deaminase; Agammaglobulinemia; Child; Humans; Intercellular Signaling Peptides and Proteins; Male; Polyarteritis Nodosa; Tumor Necrosis Factor Inhibitors
PubMed: 33901990
DOI: 10.1016/j.semarthrit.2021.04.009 -
European Journal of Internal Medicine Jun 2021To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome)... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the efficacy and safety of adjuvant therapies in newly diagnosed or relapsing giant cell arteritis (GCA) in terms of relapse rate at week 52 (primary outcome) and to assess the impact of GC tapering regimen on adjuvant effectiveness.
METHODS
For this systematic review and meta-analysis, we searched PubMed, EMBASE, CENTRAL, trial registries, from inception to November 2020. We included all randomized controlled trials (RCTs) and controlled prospective studies evaluating adjuvant treatments in GCA, without date or language restriction. Two reviewers independently selected studies, extracted data and assessed risk of bias. Quality of evidence was summarised with GRADE.
RESULTS
Of the 680 records identified, 16 studies were included (1,068 participants) evaluating various adjuvant therapies compared to GC only. No study compared adjuvants with each other. Risk of bias was high in 5/7 trials evaluating our primary outcome. Risk of relapse at week 52 was reduced for only the anti-IL6 and IL6-receptor drug class versus the control (RR=0.45, 95%CI 0.30-0.66, I2=38%), particularly tocilizumab (RR=0.38, 95%CI 0.23-0.63, I2=42%) with a moderate quality of evidence. We found no significant interaction according to GC tapering regimen. Our meta-analysis did not show a significant benefit for methotrexate. Except for dapsone, ciclosporine and hydroxychloroquine, other adjuvants did not seem to show increased risk of adverse events.
CONCLUSIONS
Tocilizumab seems to reduce the relapse rate in GCA at week 52 but the quality of evidence was moderate. No other molecule has shown efficacy. No significant interaction on relapse rate by GC tapering regimen was found.
STUDY REGISTRATION
PROSPERO CRD42020172011.
Topics: Drug Therapy, Combination; Giant Cell Arteritis; Glucocorticoids; Humans; Methotrexate; Steroids
PubMed: 33879385
DOI: 10.1016/j.ejim.2021.03.040