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BMJ Open May 2019To clarify clinical significance of the sole presence of autoantibodies for idiopathic pulmonary fibrosis (IPF) without any other symptoms or signs suggestive of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To clarify clinical significance of the sole presence of autoantibodies for idiopathic pulmonary fibrosis (IPF) without any other symptoms or signs suggestive of autoimmune disease.
DESIGN
Systematic review and meta-analysis DATA SOURCES: Medline, EMBASE, Science Citation Index Expanded and Google Scholar were searched from 1 January 2002 through 12 February 2019.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Primary studies addressing all-cause mortality and the development of a defined autoimmune disease for IPF with autoantibodies were included for the review.
DATA EXTRACTION AND SYNTHESIS
Two reviewers extracted relevant data and assessed risk of bias independently. Meta-analysis was conducted using a random-effects model if three or more studies reported the same outcome for a certain autoantibody. The quality of evidence was assessed by the Grades of Recommendation, Assessment, Development and Evaluation system.
RESULTS
Out of 4603 records retrieved nine studies were included in this review. All studies contained some risk of bias. Based on pooled data myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was significantly associated with microscopic polyangiitis incidence with risk ratio (RR) of 20.2 (95% CI: 7.22 to 56.4) and antinuclear antibody (ANA) was also significantly associated with the development of connective tissue diseases with RR of 7.11 (p=0.001) (10 cases in 157 patients with ANA) in one study. However, there was no significant association of autoantibodies with all-cause mortality aside from MPO-ANCA and proteinase 3-ANCA in one study each. MPO-ANCA was not demonstrated to be associated with all-cause mortality by meta-analysis. The quality of evidence was deemed as either low or very low.
CONCLUSIONS
The presence of autoantibodies such as MPO-ANCA and ANA was demonstrated to be associated with the development of some autoimmune diseases for patients with IPF although there was no difference of all-cause mortality. However, the results should be interpreted with caution due to low evidence level.
PROSPERO REGISTRATION NUMBER
CRD42017077336.
Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Autoimmune Diseases; Epidemiologic Methods; Female; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Peroxidase; Prognosis
PubMed: 31147365
DOI: 10.1136/bmjopen-2018-027849 -
Seminars in Arthritis and Rheumatism Dec 2020A comprehensive review of outcome measures used in randomized controlled trials (RCTs) of ANCA-associated vasculitis (AAV) could advance trial conductance for this... (Review)
Review
BACKGROUND
A comprehensive review of outcome measures used in randomized controlled trials (RCTs) of ANCA-associated vasculitis (AAV) could advance trial conductance for this disease.
METHODS
A systematic literature review of outcome measures (as specified in methods section as primary and/or secondary outcomes) in RCTs of AAV was conducted. Medline, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception until April 30, 2019 for RCTs enrolling patients with granulomatosis with polyangiitis and/or microscopic polyangiitis. Outcome measures were organized according to domains (e.g. disease activity) and instruments [e.g. Birmingham Vasculitis Activity Score (BVAS)].
RESULTS
Out of 1101 identified records, 68 RCTs were eligible. Disease activity was an outcome domain collected in 67 (98%) of the RCTs. The BVAS was the most widely used instrument for disease assessment but definitions for remissions and relapse varied for the purpose of primary endpoint definitions. Damage, most often assessed by the Vasculitis Damage Index, was an outcome in 30 (44%) of the RCTs. Mortality was specified as an outcome in 26 (38%) studies. The following outcome domains were assessed: patient-reported outcomes (PROs) in 28 (41%), drug exposure/safety in 58 (85%), and biomarkers [acute phase reactants, ANCA levels] in 24 (35%). Timing for outcome assessment differed substantially, with 3, 6, or 12 months being the most frequent time points.
CONCLUSION
Outcome measures used in trials in AAV commonly included vasculitis-specific tools for disease assessment, but with heterogeneity in endpoint-definitions and timing of assessments. Other core outcomes in AAV, including PROs, and damage measures, are often omitted in AAV trials.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Humans; Microscopic Polyangiitis; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic
PubMed: 33130459
DOI: 10.1016/j.semarthrit.2020.09.010 -
The Journal of Rheumatology Dec 2022While myocardial impairment is a predictor of poor prognosis in antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), little is known about valvular...
OBJECTIVE
While myocardial impairment is a predictor of poor prognosis in antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), little is known about valvular involvement. This study aims at describing the clinical presentation, management, and outcome of endocarditis associated with AAV.
METHODS
We conducted a multicenter retrospective study in centers affiliated with the French Vasculitis Study Group. We included patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or eosinophilic GPA with endocardial impairment. A systematic review was then performed through PubMed, Embase, and Cochrane Library from inception up to September 2020.
RESULTS
The retrospective cohort included 9 patients (82%) with GPA, 1 (9%) with MPA, and 1 (9%) with unclassified AAV. Clinical presentation included acute valvular insufficiency (n = 7, 64%), cardiac failure (n = 3, 27%), dyspnea (n = 3, 27%), and no symptoms (n = 2, 18%). The aortic valve was the most frequently affected (n = 8/10, 80%), and vegetations were noted in 4 of 10 patients (40%). Six patients (55%) underwent surgical valvular replacement. No death from endocarditis was reported. The systematic review retrieved 42 patients from 40 references: 30 (71%) had GPA, 21 (50%) presented with vegetations, the aortic valve (n = 26, 62%) was the most frequently involved. Valvular replacement was required in 20 cases (48%) and 5 patients (13%) died from the endocarditic impairment.
CONCLUSION
Endocarditis is a rare and potentially life-threatening manifestation of AAV. Acute valvular insufficiency may lead to urgent surgery. Implementing transthoracic echocardiography in standard assessment at baseline and follow-up of AAV might reduce the delay to diagnosis and allow earlier immunosuppressive treatment before surgery is needed.
Topics: Humans; Retrospective Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Microscopic Polyangiitis; Endocarditis; Cytoplasm; Granulomatosis with Polyangiitis; Multicenter Studies as Topic
PubMed: 35840158
DOI: 10.3899/jrheum.211379 -
Rheumatology (Oxford, England) Dec 2020Pleuroparenchymal fibroelastosis (PPFE) is characterized by predominantly upper lobe pleural and subjacent parenchymal fibrosis; PPFE features were described in patients...
OBJECTIVES
Pleuroparenchymal fibroelastosis (PPFE) is characterized by predominantly upper lobe pleural and subjacent parenchymal fibrosis; PPFE features were described in patients with rheumatic autoimmune diseases (RAID). A systematic literature review was performed to investigate the prevalence, prognosis and potential association of PPFE with previous immunosuppression in RAID.
METHODS
EMBASE, Web of Science and PubMed databases were questioned from inception to 1 September 2019. Articles published in English and addressing PPFE in patients with RAID were selected.
RESULTS
Twenty out of 794 papers were selected with a total of 76 cases of RAID-PPFE patients (20 SSc, 9 RA, 6 IIM6 primary SS, 5 overlap syndromes, 3 ANCA-associated vasculitides, 2 granulomatosis with polyangiitis, 1 microscopic polyangiitis, 1 UCTD, 1 SLE, 1 GCA and 21 patients with non-specified RAID). Dyspnoea was the most frequently reported symptom (37/48 patients, 77%). Patients frequently presented with a restrictive pattern and decline in diffusing lung capacity for carbon monoxide. During the follow-up, 7/12 patients had progression at imaging, 22/39 presented a generic clinical worsening, 19/38 had a functional deterioration and 15/43 remained stable.
CONCLUSION
The present systematic literature review confirms that PPFE features are present in RAID. Rheumatologists should be aware of this new radiological pattern that holds a bad prognosis.
Topics: Autoimmune Diseases; Humans; Pleural Diseases; Pulmonary Fibrosis; Rheumatic Diseases
PubMed: 33313932
DOI: 10.1093/rheumatology/keaa451 -
Value in Health Regional Issues Mar 2022Azathioprine has been the therapy of choice for the maintenance of remission in patients with antineutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis,...
Cost-Effectiveness of Rituximab (Fixed Schedule vs Tailored Dose) Compared With Azathioprine Maintenance Therapy in Adults With Generalized Antineutrophil Cytoplasm Antibody-Associated Vasculitis in Colombia.
OBJECTIVES
Azathioprine has been the therapy of choice for the maintenance of remission in patients with antineutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis, but recent studies show that rituximab could be more effective. To evaluate the cost-effectiveness of azathioprine, fixed-schedule rituximab, and tailored-dose rituximab for ANCA-associated systemic vasculitis.
METHODS
A Markov model from the perspective of the Colombian healthcare system was designed with annual cycles and a 5-year time horizon, charting the following states: remission, minor relapse, major relapse, and death. The discount rate was 5%. Transition probabilities were obtained from a systematic literature review. The costs (1 US dollar = 2956 Colombian pesos in 2018) were estimated based on national drug registries and official fee manuals for procedures, along with other resources. The main outcomes were quality-adjusted life-years (QALYs) taken from the Tufts registry. Univariate and multivariate sensitivity analyses were performed.
RESULTS
Final costs were $1446 for azathioprine, $4898 for tailored-dose rituximab, and $6311 for fixed-schedule rituximab. QALYs gained were 3.18, 4.08, and 3.98, respectively. Rituximab was cost-effective (cost per incremental QALY gained: $4919, and $6865), and tailored-dose administration had a lower cost. Sensitivity analyses did not affect the results.
CONCLUSIONS
Tailored-dose rituximab was the most cost-effective treatment for ANCA-associated vasculitis. Azathioprine presented worse effectiveness and lower cost, and fixed-schedule rituximab was dominated by tailored-dose rituximab.
Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Azathioprine; Colombia; Cost-Benefit Analysis; Cytoplasm; Humans; Rituximab
PubMed: 34922060
DOI: 10.1016/j.vhri.2021.08.002 -
Artificial Organs Jun 2021Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage...
Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.
Topics: Extracorporeal Membrane Oxygenation; Hemorrhage; Humans; Lung Diseases; Pulmonary Alveoli
PubMed: 33190331
DOI: 10.1111/aor.13861 -
Clinical Kidney Journal Oct 2018antineutrophil cytoplasmic antibody-associated vasculitis typically arises in post-reproductive years, but can occur during pregnancy. Concerns of treatment-related...
BACKGROUND
antineutrophil cytoplasmic antibody-associated vasculitis typically arises in post-reproductive years, but can occur during pregnancy. Concerns of treatment-related teratogenicity persist, while efficacy and safety of new therapies including intravenous immunoglobulin (IVIG) and rituximab are uncertain. There remains a paucity of maternal, fetal and pregnancy outcome data in these women, and therefore a lack of guidance on safe treatment for clinicians.
METHODS
We conducted a systematic review of the literature and a local, retrospective chart review of women with antibody-associated vasculitis (AAV) in pregnancy. Cochrane, Embase and PubMed databases and relevant conference abstracts were searched. Patient demographics, clinical presentation, management and outcomes (maternal, fetal and pregnancy-related) were analyzed.
RESULTS
Twenty-seven cases of AAV in pregnancy were included. Women presented were from 5 to 39 weeks' gestation, of which a majority were in the second trimester (median 20 weeks). The median gravida of women was 2 and the median parity was 1. Women were treated with steroids (89%), cyclophosphamide (CYC) (37%), other immunosuppressive agents [azathioprine (AZA), IVIG, plasma exchange (PLEX)] or no therapy (11%). High rates of serious complications, including preeclampsia (29%) and maternal death (7%), were reported; however, most pregnancies resulted in live birth (73%). Prematurity was common; 73% of live births occurred prior to 37 weeks' gestation and 40% prior to 34 weeks' gestation. The majority of infants were born in the third trimester (median 34.5 weeks). Rates of pregnancy termination were high (23%) and only one intrauterine death was reported, shortly after initiation of therapy (4%). Congenital abnormalities were rare, with one infant having a solitary, pelvic kidney (6%) after maternal treatment with steroids, CYC and PLEX. Use of PLEX, IVIG and AZA increased after 2005, whereas CYC use decreased. Remission often occurred postpartum (60%).
CONCLUSIONS
AAV in pregnancy can result in uncomplicated pregnancies; however, serious maternal risks exist. Further data on potentially pregnancy compatible therapies such as IVIG and rituximab are needed in this population.
PubMed: 30288261
DOI: 10.1093/ckj/sfy011 -
Clinical Immunology (Orlando, Fla.) Nov 2020We conducted a systematic review to identify cases of infection-induced anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
BACKGROUND
We conducted a systematic review to identify cases of infection-induced anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
METHODS
PubMed/Medline databases were searched from inception to July of 2020, according to PRISMA guidelines.
RESULTS
Among the 618 abstracts identified, 18 articles describing 23 patients (60.9% female, mean age 50.5 years) were included. Median time between infection and vasculitis development was 3 months. Five (21.7%) patients expired during follow-up. Vasculitis regressed after the resolution of infection in 12/23 (52.2%). ANCA titers decreased significantly on follow-up in 14/16 patients and in all survivors in which they were measured. Pathogens reported included Mycobacterium spp., Coccidioides spp., Rickettsia rickettsii, Staphylococcus spp., EBV, CMV and Dengue virus.
CONCLUSIONS
MPO-AAV can occur after infection and may regress after its resolution. Infection should be considered in cases of MPO-AAV, as immunosuppressive treatment can have catastrophic results if the infection is not adequately treated.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Humans; Immunosuppressive Agents; Infections; Peroxidase
PubMed: 32961330
DOI: 10.1016/j.clim.2020.108595 -
International Journal of Rheumatic... Sep 2018Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are a group of small vessel vasculitis with systemic presentations and considerable morbidity and...
AIM
Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are a group of small vessel vasculitis with systemic presentations and considerable morbidity and mortality. Pregnancy in these patients poses a significant therapeutic challenge. There is limited published literature regarding pregnancy in AAV.
METHODS
Two cases of successful pregnancy outcomes in patients with active AAV are described. A systematic review was conducted on the lines of the PRISMA statement for conducting systemic reviews: PubMed (inception of PubMed until 30 April 2017, English language only) and EmBase databases were searched using the following terms: 'pregnancy' AND 'ANCA associated vasculitis' OR 'granulomatosis with polyangiitis' OR 'eosinophilic granulomatosis with polyangiitis' OR 'microscopic polyangiitis' OR 'Churg-Strauss syndrome' OR 'Wegener's granulomatosis'.
RESULTS
One hundred and thirty-seven pregnancies were documented in 110 patients of AAV. Vasculitis diagnosis was made before pregnancy in 69, during pregnancy in 32 and after pregnancy in 9 patients. Mean age at the time of pregnancy was 29.3 ± 5.3 years. There were 91 term pregnancies, 28 were preterm pregnancies, 15 abortions and 3 still births; 78 had normal delivery and 26 had caesarian section.
CONCLUSION
Successful pregnancies have been reported in AAV patients.
Topics: Abortion, Induced; Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Female; Humans; Immunosuppressive Agents; Live Birth; Pregnancy; Pregnancy Complications, Cardiovascular; Premature Birth; Risk Factors; Rituximab; Stillbirth; Treatment Outcome; Young Adult
PubMed: 30345645
DOI: 10.1111/1756-185X.13342