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1.
J Clin Rheumatol ; 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32826657

RESUMO

BACKGROUND/OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. METHODS: This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as "probable" (supportive clinical evidence) or "possible" (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events. RESULTS: Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13-5.21]), current smokers (2.89 [1.33-6.26]), and Disease Activity Score in 28 joints-erythrocyte sedimentation rate score (1.30 [1.04-1.61]) as significant risk factors for ILD events. CONCLUSIONS: Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.

2.
Lancet Respir Med ; 8(2): 147-157, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31578169

RESUMO

BACKGROUND: At present, no approved pharmacotherapies are available for unclassifiable interstitial lung disease (ILD), which is characterised by progressive fibrosis of the lung. We aimed to assess the efficacy and safety of pirfenidone in patients with progressive fibrosing unclassifiable ILD. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 70 centres in Australia, Belgium, Canada, Czech Republic, Denmark, Germany, Greece, Ireland, Israel, Italy, Poland, Portugal, Spain, and the UK. Eligible patients (aged ≥18-85 years) had progressive fibrosing unclassifiable ILD, a percent predicted forced vital capacity (FVC) of 45% or higher and percent predicted carbon monoxide diffusing capacity (DLco) of 30% or higher, more than 10% fibrosis on high-resolution CT, and a high-resolution CT from the previous 12 months. Patients were randomly assigned (1:1) to 2403 mg oral pirfenidone daily or placebo using a central validated interactive voice or web-based response system, stratified by concomitant mycophenolate mofetil use and presence or absence of interstitial pneumonia with autoimmune features. Investigators, site personnel, and patients were masked to treatment assignment. The primary endpoint was mean predicted change in FVC from baseline over 24 weeks, measured by daily home spirometry. Secondary endpoints were change in FVC measured by site spirometry, proportion of patients who had a more than 5% or more than 10% absolute or relative decline in percent predicted FVC measured by clinic-based spirometry, change in percent predicted DLco, change in 6-min walk distance (6MWD), change in University of California San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) score, change in Leicester Cough Questionnaire score, change in cough visual analogue scale, and changes in total and subscores of the St George's Respiratory Questionnaire (SGRQ), all of which were compared with baseline. Additional secondary endpoints included proportion of patients who had non-elective hospitalisation (respiratory and all-cause) and acute exacerbations, and progression-free survival. Efficacy was analysed in the intention-to-treat (ITT) population, which included all randomly assigned patients. Safety was assessed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03099187, and is no longer recruiting. FINDINGS: Between May 15, 2017, and June 5, 2018, 253 patients were randomly assigned to receive 2403 mg pirfenidone (n=127) or placebo (n=126) and were included in the ITT analysis set. Analysis of the primary endpoint was affected by intraindividual variability in home spirometry values, which prevented application of the prespecified statistical model. Over 24 weeks, predicted median change in FVC measured by home spirometry was -87·7 mL (Q1-Q3 -338·1 to 148·6) in the pirfenidone group versus -157·1 mL (-370·9 to 70·1) in the placebo group. Over 24 weeks, predicted mean change in FVC measured by site spirometry was lower in patients given pirfenidone than placebo (treatment difference 95·3 mL [95% CI 35·9 to 154·6], p=0·002). Compared with the placebo group, patients in the pirfenidone group were less likely to have a decline in FVC of more than 5% (odds ratio [OR] 0·42 [95% CI 0·25 to 0·69], p=0·001) or more than 10% (OR 0·44 [0·23 to 0·84], p=0·011). At week 24, mean change in DLco from baseline was -0·7% (SD 7·1) for the pirfenidone group and -2·5% (8·8) for the placebo group, and mean change in 6MWD from baseline was -2·0 m (68·1) for the pirfenidone group and -26·7 m (79·3) for the placebo group. Changes from baseline in UCSD-SOBQ, Leicester Cough Questionnaire score, cough visual analogue scale, and SGRQ scores were similar between the pirfenidone and placebo groups at week 24. Analysis of acute exacerbations, hospital admissions, and time to death from respiratory causes during the study yielded no meaningful results due to a small number of events. No differences in progression-free survival were identified between the pirfenidone and placebo groups, irrespective of the definition of progression-free survival used. Treatment-emergent adverse events were reported in 120 (94%) of 127 patients in the pirfenidone group and 101 (81%) of 124 patients in the placebo group. Serious treatment-emergent adverse events were reported in 18 (14%) patients in the pirfenidone group and 20 (16%) patients in the placebo group. The most common treatment-related treatment-emergent adverse events were gastrointestinal disorders (60 [47%] in the pirfenidone group vs 32 [26%] in the placebo group), fatigue (16 [13%] vs 12 [10%]), and rash (13 [10%] vs nine [7%]). INTERPRETATION: Although the planned statistical model could not be applied to the primary endpoint data, analysis of key secondary endpoints suggests that patients with progressive fibrosing unclassifiable ILD could benefit from pirfenidone treatment, which has an acceptable safety and tolerability profile. These findings support further investigation of pirfenidone as an effective treatment for patients with progressive fibrotic unclassifiable ILD. FUNDING: F Hoffmann-La Roche.

3.
Lung ; 197(6): 709-713, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31583453

RESUMO

OBJECTIVE: To describe the phenotypic characteristics and natural history of patients with autoimmune forms of interstitial lung disease (ILD). METHODS: Retrospective, descriptive, single-center study of patients with autoimmune forms of ILD evaluated between February 2008 and August 2014. All data were extracted from the electronic medical record. Longitudinal changes in forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLco%) in percent predicted were analyzed and time-to-event analyses for death were performed using Cox regression. RESULTS: Of the entire cohort (n = 243), systemic sclerosis (SSc)-associated ILD (n = 88, 36%), interstitial pneumonia with autoimmune features (IPAF, n = 56, 23%), rheumatoid arthritis (RA)-associated ILD (n = 42, 17%), and idiopathic inflammatory myopathy (IIM)-associated ILD (n = 26, 11%) were the most common phenotypes. The SSc-ILD, IIM-ILD, and IPAF groups had similar features: average age in the mid-50s, strongly female predominant and more likely to have nonspecific interstitial pneumonia (NSIP). In contrast, RA-ILD patients were older, gender balanced, more likely to be past smokers and were UIP predominant. Adjusted longitudinal lung function was stable during a median follow-up period of nearly 4 years and the independent predictors for death were older age (p = 0.003), male sex (p = 0.019), and lower FVC (p = < 0.001). CONCLUSIONS: The predominant phenotypes of autoimmune ILD were SSc-ILD, IPAF, RA-ILD, and IIM-ILD. In contrast to the other subsets, those with RA-ILD may be older, gender balanced, with more smoking history, and higher proportion of UIP. Longitudinal lung function was stable among the groups and younger age, female gender, and better lung function were associated with improved survival.

4.
Clin Rheumatol ; 38(10): 2673-2681, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31423560

RESUMO

Interstitial lung disease (ILD) is a common manifestation of systemic autoimmune diseases and a leading cause of death in these patients. A proportion of patients with autoimmune ILDs develop a progressive fibrosing form of ILD, characterized by increasing fibrosis on high-resolution computed tomography, worsening of lung function, and early mortality. Autoimmune disease-related ILDs have a variable clinical course and not all patients will require treatment, but all patients should be monitored for signs of progression. Apart from systemic sclerosis-associated ILD, the limited evidence to support the efficacy of immunosuppression as a treatment for ILDs is based mainly on small retrospective series and expert opinion. Non-clinical data suggest that there are commonalities in the mechanisms that drive progressive fibrosis in ILDs with an immunological trigger as in other forms of progressive fibrosing ILD. This suggests that nintedanib and pirfenidone, drugs known to slow disease progression in patients with idiopathic pulmonary fibrosis, may also slow the progression of ILD associated with systemic autoimmune diseases. In the SENSCIS® trial, nintedanib reduced the rate of ILD progression in patients with systemic sclerosis-associated ILD. The results of other large clinical trials will provide further insights into the role of anti-fibrotic therapies in the treatment of autoimmune disease-related ILDs.


Assuntos
Doenças Autoimunes/complicações , Doenças Pulmonares Intersticiais/complicações , Pulmão/fisiopatologia , Fibrose Pulmonar/complicações , Artrite Reumatoide/complicações , Artrite Reumatoide/terapia , Doenças Autoimunes/terapia , Ensaios Clínicos como Assunto , Progressão da Doença , Humanos , Imunossupressão/efeitos adversos , Indóis/uso terapêutico , Estimativa de Kaplan-Meier , Doenças Pulmonares Intersticiais/terapia , Fenótipo , Fibrose Pulmonar/terapia , Piridonas/uso terapêutico , Fatores de Risco , Tomografia Computadorizada por Raios X
5.
Clin Chest Med ; 40(3): 609-616, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31376895

RESUMO

The European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease put forth the research classification interstitial pneumonia with autoimmune features as a step toward uniformly describing these patients. Diverse nomenclature and classification schemes had been proposed to characterize them. This classification has provided uniform nomenclature and criteria, fostering interdisciplinary engagement and research. Longitudinal surveillance is needed; some patients evolve to a defined connective tissue disease. This review discusses cohort studies of interstitial pneumonia with autoimmune features and what they have taught us about the phenotype, and offers insights into future directions.


Assuntos
Doenças Autoimunes/etiologia , Doenças Pulmonares Intersticiais/imunologia , Doenças Autoimunes/patologia , Humanos , Estudos Retrospectivos
7.
Curr Med Res Opin ; 35(11): 2015-2024, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31328965

RESUMO

Objective: Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) develop a progressive fibrosing phenotype. We investigated the diagnosis and management of non-IPF ILDs using data from a survey of physicians and from US insurance claims. Methods: Pulmonologists, rheumatologists and internists in France, Germany, Italy, Japan, Spain, UK and US who had managed ≥10 patients with non-IPF ILDs in the past year, including those with progressive fibrosing ILDs, completed an online survey. Data on US insurance and prescription claims were obtained from a repository that aggregates data on claims routed from providers or pharmacies to payers. Results: In May-June 2017, 243 pulmonologists, 203 rheumatologists and 40 internists completed an online survey. Respondents estimated that 18-32% of patients diagnosed with non-IPF ILDs develop progressive fibrosis and that time from symptom onset to death in these patients was 61-80 months. Drug treatment was given to 50-75% of patients with non-IPF progressive fibrosing ILDs. Reasons for patients not being treated included that physicians considered patients to have mild or slowly progressing disease, or did not believe that available treatments are effective or well tolerated. Corticosteroids were the preferred first-line treatment for all types of non-IPF ILD. There was considerable heterogeneity in preferences for second- and third-line treatments. US insurance claims data from 3823 patients indicated that, in 2016, 50-75% of patients with ILDs received drug treatment (mostly corticosteroids) for their ILD. Conclusions: Physicians estimate that 18-32% of patients diagnosed with non-IPF ILDs develop a progressive fibrosing phenotype and that these patients experience significant delays in the diagnosis of ILD and the detection of progressive fibrosis. Between 25% and 50% of patients with progressive fibrosing ILDs do not receive drug therapy. There is an unmet need for effective and well tolerated treatments for progressive fibrosing ILDs.

8.
N Engl J Med ; 380(26): 2518-2528, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31112379

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS ClinicalTrials.gov number, NCT02597933.).


Assuntos
Inibidores Enzimáticos/uso terapêutico , Indóis/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Escleroderma Sistêmico/complicações , Administração Oral , Adulto , Diarreia/induzido quimicamente , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Indóis/efeitos adversos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/tratamento farmacológico , Capacidade Vital
9.
Adv Ther ; 36(5): 1100-1113, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30929184

RESUMO

INTRODUCTION: Interstitial lung disease (ILD) is a common manifestation of scleroderma/systemic sclerosis (SSc). However, the direct and indirect economic burdens of SSc-ILD remain unclear. This study assessed and compared healthcare resource utilization (HRU), direct healthcare costs, work loss, and indirect costs between patients with SSc-ILD and matched controls with neither SSc nor ILD in the USA. METHODS: Data were obtained from a large US commercial claims database (2005-2015). Patients (at least 18 years old) had at least one SSc diagnosis in the inpatient (IP) or emergency room (ER) setting or at least two SSc diagnoses in another setting, and at least one diagnosis of ILD in the IP or ER setting or at least two diagnoses of ILD in another setting. Controls with neither SSc nor ILD were matched 5:1 to patients with SSc-ILD. Comparisons were conducted using Wilcoxon signed-rank and McNemar's tests and adjusted odds ratios (ORs) and incidence rate ratios (IRRs). RESULTS: A total of 479 SSc-ILD patients and 2395 matched controls were included (52 SSc-ILD patients and 260 matched controls for work loss and indirect cost analyses). Patients with SSc-ILD had significantly higher HRU and costs, IP admissions (adjusted IRR = 5.6), IP hospitalization days (adjusted IRR = 12.0), ER visits (adjusted IRR = 2.8), OP visits (adjusted IRR = 3.1), and days of work loss (adjusted IRR = 4.5). The adjusted difference in annual direct healthcare costs was $28,632 (SSc-ILD, $33,195; controls, $4562) and that in indirect costs was $4735 (SSc-ILD, $5640; controls, $906) (all p < 0.0001). CONCLUSION: SSc-ILD patients had significantly higher HRU, work loss, and direct and indirect costs compared to matched controls with neither SSc nor ILD. FUNDING: Boehringer Ingelheim Pharmaceuticals, Inc.


Assuntos
Recursos em Saúde/economia , Seguro Saúde/economia , Doenças Pulmonares Intersticiais/economia , Doenças Pulmonares Intersticiais/terapia , Escleroderma Sistêmico/economia , Escleroderma Sistêmico/terapia , Adulto , Comorbidade , Efeitos Psicossociais da Doença , Análise de Dados , Bases de Dados Factuais , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Recursos em Saúde/estatística & dados numéricos , Hospitalização/economia , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/epidemiologia
10.
Eur Respir Rev ; 28(151)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30814139

RESUMO

Patients with certain types of fibrosing interstitial lung disease (ILD) are at risk of developing a progressive phenotype characterised by self-sustaining fibrosis, decline in lung function, worsening quality of life, and early mortality. It has been proposed that such progressive fibrosing ILDs, which show commonalities in clinical behaviour and in the pathogenetic mechanisms that drive progressive fibrosis, may be "lumped" together for the purposes of clinical research and, potentially, for treatment. At present, no drugs are approved for the treatment of ILDs other than nintedanib and pirfenidone for the treatment of idiopathic pulmonary fibrosis. For other progressive fibrosing ILDs, the mainstay of drug therapy is immunosuppression. However, it is postulated that, once the response to lung injury in fibrosing ILDs has reached the stage at which fibrosis has become progressive and self-sustaining, targeted antifibrotic therapy would be required to slow disease progression. Nintedanib, an intracellular inhibitor of tyrosine kinases, has shown antifibrotic, anti-inflammatory and vascular remodelling effects in several non-clinical models of fibrosis, irrespective of the trigger for the injury. Ongoing clinical trials will provide insight into the role of antifibrotic treatment with nintedanib or pirfenidone in the management of fibrosing ILDs with a progressive phenotype.


Assuntos
Doenças Pulmonares Intersticiais , Pulmão , Fibrose Pulmonar , Progressão da Doença , Nível de Saúde , Humanos , Indóis/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/fisiopatologia , Fenótipo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/mortalidade , Fibrose Pulmonar/patologia , Fibrose Pulmonar/fisiopatologia , Piridonas/uso terapêutico , Qualidade de Vida , Fármacos do Sistema Respiratório/uso terapêutico , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
11.
J Rheumatol ; 46(8): 920-927, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30770505

RESUMO

OBJECTIVE: To quantify healthcare resource utilization (HRU), work loss, and annual direct and indirect healthcare costs among patients with systemic sclerosis (SSc) compared to matched controls in the United States. METHODS: Data were obtained from a large US commercial claims database. Patients were ≥ 18 years old at the index date (first SSc diagnosis) and had ≥ 1 SSc diagnosis in the inpatient (IP) or emergency room (ER) setting, or ≥ 2 SSc diagnoses on 2 different dates in the outpatient (OP) setting between January 1, 2005, and March 31, 2015; continuous enrollment was required during the followup period (12 months after the index date). Individuals with no SSc diagnoses were matched 1:1 to patients with SSc. Wilcoxon signed-rank and McNemar tests were used for comparisons and regressions with generalized estimating equations for adjusted OR (aOR) and incidence rate ratios (IRR) between 2 cohorts. RESULTS: There were 2192 pairs of patients with SSc and matched controls included (mean age 57.6 yrs; 84.3% female); of these, 233 were eligible for work loss/indirect cost analyses. Compared to matched controls, patients with SSc had significantly higher HRU and costs during the 1-year followup period, IP admissions (adjusted IRR = 2.4), IP hospitalization days (adjusted IRR = 3.1), ER visits (adjusted IRR = 2.0), OP visits (adjusted IRR = 2.3), and days of work loss (adjusted IRR = 2.6). The adjusted difference in annual direct and indirect costs was US$12,820 and $3103, respectively (all p < 0.0001). CONCLUSION: Patients with SSc had a high direct and indirect economic burden postdiagnosis.

13.
Chest ; 155(2): 263-264, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30732689
14.
Arthritis Rheumatol ; 71(2): 182-195, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30604506
16.
Ann Am Thorac Soc ; 16(5): 525-533, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30695649

RESUMO

Interstitial pneumonia with autoimmune features (IPAF) is a research classification proposed by the European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease as an initial step to uniformly define, identify, and study patients with interstitial lung disease (ILD) who have features of autoimmunity, yet fall short of a characterizable connective tissue disease. Since its publication in July 2015, there has been substantial interest in IPAF. Centers from around the world have published their findings of retrospectively identified cohorts of patients who fulfill IPAF criteria, suggestions for modification of the criteria have been offered, and patients who fulfill IPAF criteria are being included as a subset in the ongoing phase II multicenter unclassifiable ILD treatment trial with pirfenidone. The IPAF designation represents an important first step toward studying and furthering our understanding of the natural history of this cohort of patients with ILD using uniform nomenclature and a standardized set of criteria. Prospective evaluations and, ideally, interdisciplinary and multicenter collaborations will inform best practices for treatment and management and will guide future refinement to the IPAF criteria. This review focuses on the relevant background that led to the development of IPAF, summarizes the proposed criteria, discusses cohort studies of patients with IPAF published to date and what they have taught us about the IPAF phenotype, and offers insights into future directions in this arena. Clinical trial registered with www.clinicaltrials.gov (NCT03099187).


Assuntos
Doenças Autoimunes/imunologia , Autoimunidade , Doenças Pulmonares Intersticiais/imunologia , Doenças Autoimunes/diagnóstico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico
17.
J Rheumatol ; 46(4): 360-369, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30442831

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) is commonly associated with rheumatoid arthritis (RA) and can have significant morbidity and mortality. The objective of this study was to calculate the prevalence, incidence, healthcare costs, and mortality of RA-related ILD (RA-ILD) in the United States. METHODS: This retrospective cohort analysis used the Truven Health MarketScan Commercial and Medicare Supplemental health insurance databases from 2003 to 2014 and the Social Security Administration death database. Patients with RA-ILD were selected based on diagnoses on medical claims. Outcomes were 1-year prevalence and incidence of RA-ILD among the general enrollee population, all-cause and respiratory-related healthcare costs (2014 US$), and all-cause survival for a subset of newly diagnosed patients with vital status information. This analysis was descriptive. No statistical testing was conducted. RESULTS: Prevalence of RA-ILD ranged from 3.2 to 6.0 cases per 100,000 people across the 10-year period and incidence ranged from 2.7 to 3.8 cases per 100,000 people. There were 750 incident patients with 5 years of followup data. Over that time, 72% had an inpatient admission and 76% had an emergency room visit. Mean total 5-year costs were US$173,405 per patient (SD $158,837). Annual per-patient costs were highest in years 1 and 5. At 5 years after first diagnosis in the data, 35.9% of patients had died. CONCLUSION: Prevalence of RA-ILD increased over time. For patients who could be followed over a 5-year period, healthcare use and costs were somewhat stable over time, but were substantial. RA-ILD is associated with decreased survival.

18.
J Rheumatol ; 46(2): 176-183, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30275260

RESUMO

OBJECTIVE: We sought to identify predictors of mortality and cardiopulmonary hospitalizations in patients at risk for pulmonary hypertension (PH) and enrolled in PHAROS, a prospective cohort study to investigate the natural history of PH in systemic sclerosis (SSc). METHODS: The at-risk population for PH was defined by the following entry criteria: echocardiogram systolic pulmonary arterial pressure > 40 mmHg, or DLCO < 55% predicted or ratio of % forced vital capacity/%DLCO > 1.6, measured by pulmonary function testing. Baseline clinical measures were evaluated as predictors of hospitalization and death between 2005 and 2014. Cox proportional hazards models were censored at date of PH onset or latest study visit and adjusted for age, sex, race, and disease duration. RESULTS: Of the 236 at-risk subjects who were followed for a median of 4 years (range 0.4-8.5 yrs), 35 developed PH after entering PHAROS (reclassified as PH group). In the at-risk group, higher mortality was strongly associated with male sex, low %DLCO, exercise oxygen desaturation, anemia, abnormal dyspnea scores, and baseline pericardial effusion. Risks for cardiopulmonary hospitalization were associated with increased dyspnea and pericardial effusions, although PH patients with DLCO < 50% had the highest risk of cardiopulmonary hospitalizations. CONCLUSION: Risk factors for poor outcome in patients with SSc who are at risk for PH were similar to others with SSc-PH and SSc-pulmonary arterial hypertension, including male sex, DLCO < 50%, exercise oxygen desaturation, and pericardial effusions. This group should undergo right heart catheterization and receive appropriate intervention if PH is confirmed.

19.
Mayo Clin Proc ; 94(2): 309-325, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30558827

RESUMO

Lung involvement in connective tissue diseases is associated with substantial morbidity and mortality, most commonly in the form of interstitial lung disease, and can occur in any of these disorders. Patterns of interstitial lung disease in patients with connective tissue disease are similar to those seen in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis. It may be difficult to distinguish between the 2 ailments, particularly when interstitial lung disease presents before extrapulmonary manifestations of the underlying connective tissue disease. There are important clinical implications in achieving this distinction. Given the complexities inherent in the management of these patients, a multidisciplinary evaluation is needed to optimize the diagnostic process and management strategies. The aim of this article was to summarize an approach to diagnosis and management based on the opinion of experts on this topic.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Doenças Pulmonares Intersticiais , Pulmão/diagnóstico por imagem , Fibrose Pulmonar , Biópsia , Doenças do Tecido Conjuntivo/diagnóstico , Saúde Global , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Morbidade/tendências , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/etiologia , Testes de Função Respiratória , Taxa de Sobrevida/tendências , Tomografia Computadorizada por Raios X
20.
BMJ Open Respir Res ; 5(1): e000289, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233802

RESUMO

Introduction: Despite extensive multidisciplinary team (MDT) assessment, some patients have interstitial lung disease (ILD) that is considered unclassifiable (uILD), for which there are currently no approved treatments. This study will assess the efficacy and safety of the antifibrotic pirfenidone in treating uILD. Methods and analysis: This double-blind, randomised, placebo-controlled phase II trial is enrolling adults with fibrosing ILD, including uILD that fulfils proposed research criteria for interstitial pneumonia with autoimmune features (IPAF), that cannot be classified with moderate or high confidence to any category of ILD following MDT discussion. Study participants must have >10% fibrosis on high-resolution CT scan within the previous 12 months, forced vital capacity (FVC) ≥45% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised to receive 801 mg pirfenidone or placebo three times daily for 24 weeks. The efficacy of pirfenidone vs placebo will be assessed by daily measurement of FVC using a handheld spirometer over the treatment period. Other functional parameters, patient-reported outcomes, samples for biomarker analysis and safety endpoints will be collected. Additionally, the study will assess the efficacy and safety of pirfenidone with and without concomitant mycophenolate mofetil treatment and in study participants with or without IPAF. Ethics and dissemination: This trial is being conducted in accordance with the International Conference on Harmonisation E6 guideline for Good Clinical Practice, Declaration of Helsinki and local laws for countries in which the research is conducted. Trial registration number: NCT03099187.

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