Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.

Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials.

Importance: There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective: To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, Setting, and Participants: The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2. Interventions: Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks. Main Outcomes and Measures: The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George's Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life). Results: At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was -124.6 mL (95% CI, -178.0 to -71.2 mL) with 600 mg of ziritaxestat vs -147.3 mL (95% CI, -199.8 to -94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, -52.3 to 97.6 mL]), and -173.9 mL (95% CI, -225.7 to -122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, -26.7 mL [95% CI, -100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was -173.8 mL (95% CI, -209.2 to -138.4 mL) with 600 mg of ziritaxestat vs -176.6 mL (95% CI, -211.4 to -141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, -46.9 to 52.4 mL]) and -174.9 mL (95% CI, -209.5 to -140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, -47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo. Conclusions and Relevance: Ziritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment. Trial Registration: ClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444.

Anti-MDA5-positive dermatomyositis and remission in a single referral centre population.

OBJECTIVES: To describe a single-centre North American adult cohort of anti-MDA5-positive dermatomyositis patients, with emphasis on drug-free long-term remission. METHODS: We conducted an observational retrospective cohort study of anti-MDA5-positive DM patients. All consented patients seen in the Johns Hopkins Myositis Centre from 2003-2020 with suspected muscle disease were routinely screened for myositis-specific autoantibodies. All sera were screened for anti-MDA5 autoantibodies by line blot; positives were verified by enzyme-linked immunoassay. Patients whose sera were anti-MDA5 positive by both assays (n=52) were followed longitudinally. If clinical status was unavailable, structured telephone interviews were conducted. Clinical remission was defined as being off all immunosuppression >1 year while remaining asymptomatic. RESULTS: 38/52 (73%) of the patients were women with a median age at disease-onset of 47 (IQR 40-54). Twenty-five of the patients (48%) were White, 16 (30%) were Black and 3 (6%) were Asian. Most patients (42/52, 80%) had interstitial lung disease, defined by inflammatory or fibrotic changes on high resolution computed tomography (HRCT). 18/52 (35%) of patients required pulse-dose methylprednisolone, 4/52 (8%) experienced spontaneous pneumothorax/pneumomediastinum, 6/52 (12%) required intubation, and 5/52 (10%) died. Over longitudinal follow-up (median 3.5 years), 9 (18%) patients achieved clinical remission. The median time from symptom onset to clinical remission was 4 years, and the median duration of sustained remission was 3.5 years (range 1.4-7.8). No demographic or disease characteristics were significantly associated with remission. CONCLUSIONS: In this single centre, tertiary referral population of anti-MDA5-positive dermatomyositis, ~20% of patients experienced long-term drug-free remission after a median disease duration of 4 years. No clinical or biologic factors were associated with clinical remission.

Diagnosis and Management of Myositis-Associated Lung Disease.

Although interstitial lung disease (ILD) is a leading cause of morbidity and mortality in patients with inflammatory myopathies, the current definition and diagnostic criteria of autoimmune myositis remain inadequate to capture the large proportion of patients with lung-dominant disease. As a result, these patients present unique diagnostic and treatment challenges for even the most experienced clinicians. This article highlights the emerging role of autoantibodies in the diagnosis, classification, and management of patients with ILD. We propose alternative nomenclature to facilitate research on this unique patient population. Additionally, evidence supporting the various therapies used in the treatment of myositis-associated ILD is reviewed. The classification and treatment of patients with myositis-associated ILD remains challenging. A standardized therapeutic approach to these patients is lacking, and prospective studies in the field are needed to determine optimal treatment regimens.

Clinical Subgroups and Factors Associated With Progression in Patients With Inclusion Body Myositis.

BACKGROUND AND OBJECTIVES: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in individuals older than 50 years. The disorder is slowly progressive, and although many therapies have been investigated, response has generally been poor. Clinical heterogeneity may influence treatment responsiveness; however, data regarding heterogeneity in IBM are limited and often conflicting. We aim to identify clinically distinct subgroups within a large IBM cohort and prognostic factors for disease progression. METHODS: Clinical, histologic, radiologic, and electrophysiologic data were analyzed for all patients with IBM and other forms of myositis enrolled in a longitudinal cohort from The Johns Hopkins Myositis Center from 2003 to 2018. Patients with IBM were included if they met at least one of the following criteria: Griggs possible, European Neuromuscular Centre 2011 probable, or Lloyd-Greenberg data-derived criteria for IBM. Univariate, multivariate, and graphical analyses were used to identify prognostic factors in patients with IBM. Thus, linear and logistic regressions were used to adjust for potential confounding variables. The evolution of creatine kinase and muscle strength was studied using multilevel linear regression models. Nonmodifiable risk factors (sex, race, disease duration, and age at the onset of first symptoms) were used as adjusting covariates for the regression analyses. RESULTS: Among the 335 patients meeting the inclusion criteria for IBM, 64% were male with an average age of disease onset of 58.7 years and delay to diagnosis of 5.2 years. Initial misdiagnosis (52%) and immunosuppressant treatment (42%) were common. Less than half (43%) of muscle biopsies demonstrated all 3 pathologic hallmarks: endomysial inflammation, mononuclear cell invasion, and rimmed vacuoles. Black patients had significantly weaker arm abductors, hip flexors, and knee flexors compared with non-Black patients. Female patients had stronger finger flexors and knee extensors compared with their male counterparts. Younger age (<50 years) at onset was not associated with increased weakness. DISCUSSION: Our study demonstrates that female and Black patients have distinct clinical phenotypes and trajectories within the overarching IBM clinical phenotype. These subgroups may have different responses to therapies, which may influence the design of future clinical trials in IBM.

Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study.

BACKGROUND: Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18-85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871. FINDINGS: From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group; OR 0·67 [95% CI 0·22 to 2·03]; p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (-66 vs -146; p=0·0082) and FVC% (-1·02 vs -3·21; p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group; OR 0·52 [95% CI 0·14-1·90]; p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group; OR 0·68 [0·30-1·54]; p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths. INTERPRETATION: Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials. FUNDING: Genentech.

Rapidly progressive interstitial lung disease in patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis: serial changes on HRCT.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies in patients with dermatomyositis are associated with rapidly progressive interstitial lung disease (RP-ILD). Computed tomography (CT) plays a central role in the diagnosis of RP-ILD and may help characterize the temporal changes. METHODS: We report five anti-MDA5-positive dermatomyositis patients with serial CT scans spanning their acute RP-ILD disease course. RESULTS: Our case series highlights the variable imaging pattern that can manifest in this setting, including diffuse alveolar damage and nonspecific interstitial pneumonia patterns. Three patients in our series died within 4 months of their disease onset, whereas the other two patients survived. CONCLUSION: The serial CT changes in anti-MDA5 disease are dynamic and variable; therefore, it is imperative to maintain a broad differential when faced with these HRCT patterns to improve the diagnosis and management of this underrecognized entity.

The telemedicine experience: using principles of clinical excellence to identify disparities and optimize care.

ABSTRACT: The use of telemedicine has increased significantly during the Corona virus disease 2019 pandemic. This manuscript serves to identify the underlying principles of clinical excellence in telemedicine and to determine whether effective care practices can be generalized as a one-size-fits-all model or must instead be tailored to individual patient populations.A survey assessing care quality and patient satisfaction for patients using telemedicine was created and administered via email to 2 urban cohorts of varying demographics and socioeconomic backgrounds: a population of patients with prior stroke and cerebrovascular disease, and a cohort of patients followed for interstitial lung disease. Results were compared across groups to determine the generalizability of effective practices across populations.Individuals taking part in telemedicine were more likely to be White, more affluent, and woman, regardless of clinical diagnosis compared with a similar cohort of patients seen in-person the year prior. A lower-than-expected number of patients who were Black and of lower socioeconomic status followed up virtually, indicating potential barriers to access. Overall, patients who participated in televisits were satisfied with the experience and felt that the care met their medical needs; however, those who were older were more likely to experience technical difficulties and prefer in-person visits, while those with less education were less likely to feel that their questions were addressed in an understandable way.When thoughtfully designed, telemedicine practices can be an effective model for patient care, though implementation must consider population characteristics including age, education, and socioeconomic status, and strategies such as ease of access versus optimization of communication strategies should be tailored to meet individual patient needs.

Provider Perspectives on and Access to Palliative Care for Patients With Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in profound symptom burden and carries high mortality. Palliative care (PC) is dedicated to improving quality of life in patients with serious illness. Early PC provision improves rates of advance care planning and symptom management in patients with ILD. RESEARCH QUESTION: What are the current perspectives on PC among ILD providers, and what are the barriers to PC in ILD specialty centers? STUDY DESIGN AND METHODS: A 24-question electronic survey was disseminated to providers at the 68 Pulmonary Fibrosis Foundation Care Centers across the United States from October 2020 to December 2020. RESULTS: The survey was completed by 128 participants representing all 68 Pulmonary Fibrosis Foundation Care Center Network sites. Most respondents were physicians. Most providers exhibit good knowledge of, feel comfortable assessing a patient's readiness for, and agree with the need for PC for patients with ILD. Providers are most likely to refer to PC at objective disease and/or symptomatic progression rather than at initial diagnosis. In comparison with providers who report referring their patients to PC, providers who report rare referral are more likely to cite lack local PC availability (P < .01) and less likely to feel comfortable discussing prognosis/disease trajectory (P = .03) or feel it is important to address advance directives in ILD clinic (P = .02). There is a lack of standardized measures used to assess specific symptoms, overall symptom burden, or health-related quality of life across institutions. Discordance exists between self-reported and actual access to local inpatient and outpatient PC services. INTERPRETATION: Most ILD providers use PC and are comfortable discussing PC. Barriers to PC identified in this survey include the following: perceived lack of local access to PC, lack of systematic tools to assess symptom burden, lack of established optimal timing of PC referral, and unclear need for specialized PC delivery.

Predictors of mortality in subjects with progressive fibrosing interstitial lung diseases.

BACKGROUND AND OBJECTIVE: Demographic and clinical variables, measured at baseline or over time, have been associated with mortality in subjects with progressive fibrosing interstitial lung diseases (ILDs). We used data from the INPULSIS trials in subjects with idiopathic pulmonary fibrosis (IPF) and the INBUILD trial in subjects with other progressive fibrosing ILDs to assess relationships between demographic/clinical variables and mortality. METHODS: The relationships between baseline variables and time-varying covariates and time to death over 52 weeks were analysed using pooled data from the INPULSIS trials and, separately, the INBUILD trial using a Cox proportional hazards model. RESULTS: Over 52 weeks, 68/1061 (6.4%) and 33/663 (5.0%) subjects died in the INPULSIS and INBUILD trials, respectively. In the INPULSIS trials, a relative decline in forced vital capacity (FVC) >10% predicted within 12 months (hazard ratio [HR] 3.77) and age (HR 1.03 per 1-year increase) were associated with increased risk of mortality, while baseline FVC % predicted (HR 0.97 per 1-unit increase) and diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 0.77 per 1-unit increase) were associated with lower risk. In the INBUILD trial, a relative decline in FVC >10% predicted within 12 months (HR 2.60) and a usual interstitial pneumonia-like fibrotic pattern on HRCT (HR 2.98) were associated with increased risk of mortality, while baseline DLCO % predicted (HR 0.95 per 1-unit increase) was associated with lower risk. CONCLUSION: These data support similarity in the course of lung injury between IPF and other progressive fibrosing ILDs and the value of FVC decline as a predictor of mortality.

Assessing predictors of rheumatoid arthritis-associated interstitial lung disease using quantitative lung densitometry.

OBJECTIVE: To assess predictors of subclinical RA-associated interstitial lung disease (RA-ILD) using quantitative lung densitometry (qLD). METHODS: RA patients underwent multi-detector row CT scanning at baseline and after an average of 39 months. Scans were analysed with qLD for the percentage of lung parenchyma with high attenuation areas (%HAA: the percentage of voxels of -600 to -250 Hounsfield units). Additionally, a pulmonary radiologist calculated an expert radiologist scoring (ERS) for RA-ILD features. Generalized linear models were used to identify indicators of baseline %HAA and predictors of %HAA change. RESULTS: Baseline %HAA was assessed in 193 RA patients and 106 had repeat qLD assessment. %HAA was correlated with ERS (Spearman's rho = 0.261; P < 0.001). Significant indicators of high baseline %HAA (>10% of lung parenchyma with high attenuation) included female sex, higher pack-years of smoking, higher BMI and anti-CCP ≥200 units, collectively contributing an area under the receiver operator curve of 0.88 (95% CI 0.81, 0.95). Predictors of %HAA increase, occurring in 49% with repeat qLD, included higher baseline %HAA, presence of mucin 5B (MUC5B) minor allele and absence of HLA-DRB1 shared epitope (area under the receiver operator curve = 0.69; 95% CI 0.58, 0.79). The association of the MUC5B minor allele with %HAA change was higher among men and those with higher cumulative smoking. Within the group with increased %HAA, anti-CCP level was significantly associated with a greater increase in %HAA. CONCLUSIONS: %HAA, assessed with qLD, was linked to several known risk factors for RA-ILD and may represent a more quantitative method to identify RA-ILD and track progression than expert radiologist interpretation.

Anti-Cortactin Autoantibodies Are Associated With Key Clinical Features in Adult Myositis But Are Rarely Present in Juvenile Myositis.

OBJECTIVE: To define the prevalence and clinical phenotype of anti-cortactin autoantibodies in adult and juvenile myositis. METHODS: In this longitudinal cohort study, anti-cortactin autoantibody titers were assessed by enzyme-linked immunosorbent assay in 670 adult myositis patients and 343 juvenile myositis patients as well as in 202 adult healthy controls and 90 juvenile healthy controls. The prevalence of anti-cortactin autoantibodies was compared among groups. Clinical features of patients with and those without anti-cortactin autoantibodies were also compared. RESULTS: Anti-cortactin autoantibodies were more common in adult dermatomyositis (DM) patients (15%; P = 0.005), particularly those with coexisting anti-Mi-2 autoantibodies (24%; P = 0.03) or anti-NXP-2 autoantibodies (23%; P = 0.04). In adult myositis, anti-cortactin was associated with DM skin involvement (62% of patients with anti-cortactin versus 38% of patients without anti-cortactin; P = 0.03), dysphagia (36% versus 17%; P = 0.02) and coexisting anti-Ro 52 autoantibodies (47% versus 26%; P = 0.001) or anti-NT5c1a autoantibodies (59% versus 33%; P = 0.001). Moreover, the titers of anti-cortactin antibodies were higher in patients with interstitial lung disease (0.15 versus 0.12 arbitrary units; P = 0.03). The prevalence of anti-cortactin autoantibodies was not different in juvenile myositis patients (2%) or in any juvenile myositis subgroup compared to juvenile healthy controls (4%). Nonetheless, juvenile myositis patients with these autoantibodies had a higher prevalence of "mechanic's hands" (25% versus 7%; P = 0.03), a higher number of hospitalizations (2.9 versus 1.3; P = 0.04), and lower peak creatine kinase values (368 versus 818 IU/liter; P = 0.02) than those without anti-cortactin. CONCLUSION: The prevalence of anti-cortactin autoantibodies is increased in adult DM patients with coexisting anti-Mi-2 or anti-NXP-2 autoantibodies. In adults, anti-cortactin autoantibodies are associated with dysphagia and interstitial lung disease.

Performance of the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology Classification Criteria for Idiopathic Inflammatory Myopathies in Patients With Myositis-Specific Autoantibodies.

OBJECTIVE: We undertook this study to 1) determine the sensitivity of the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) to properly classify myositis-specific autoantibody (MSA)-positive myositis patients, 2) describe the phenotype and muscle involvement over time in different MSA-positive patients, and 3) compare MSA subgroups to EULAR/ACR criteria-defined myositis subgroups for their capacity to predict clinical phenotypes in patients with IIMs. METHODS: The study included 524 MSA-positive myositis patients from the Johns Hopkins Myositis Center. Each patient was classified using the EULAR/ACR classification criteria. Patient phenotypes were summarized using factor analysis of mixed data (FAMD). We compared the ability of MSAs to that of the EULAR/ACR classification subgroups to predict the phenotype of patients by applying the Akaike information criterion (AIC) and the Bayesian information criteria (BIC) to the linear regression models. RESULTS: Overall, 91% of MSA-positive patients met the EULAR/ACR criteria to be classified as having myositis. However, 20% of patients with anti-hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) and 50% of patients with anti-PL-7 were incorrectly classified as not having myositis. Furthermore, ~10% of patients with anti-signal recognition particle (anti-SRP) and patients with anti-HMGCR were misclassified as having inclusion body myositis. FAMD demonstrated that patients within each MSA-defined subgroup had similar phenotypes. Application of both the AIC and BIC to the linear regression models revealed that MSAs were better predictors of myositis phenotypes than the subgroups defined by the EULAR/ACR criteria. CONCLUSION: Although the EULAR/ACR criteria successfully classified 91% of MSA-positive myositis patients, certain MSA-defined subgroups, including those with autoantibodies against HMGCR, SRP, and PL-7, are frequently misclassified. In myositis patients with MSAs, autoantibodies outperform the EULAR/ACR-defined myositis subgroups in predicting the clinical phenotypes of patients. These findings underscore the need to include MSAs in a revised myositis classification scheme.

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC.

INTRODUCTION: Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti-programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development. METHODS: Patients were included if they completed greater than or equal to 1 PFT within 2 years preceding ICI initiation. CIP status (CIP+: developed CIP, CIP-: did not develop CIP) was determined clinically. Generalized estimating equation-based linear regression was used to evaluate the effects of time and CIP on lung function. Primary outcomes included the following: percent-predicted forced expiratory volume in 1 second (FEV1pp), percent-predicted forced vital capacity (FVCpp), and FEV1/FVC. RESULTS: A total of 43 patients (34 CIP-, 9 CIP+) with 79 PFTs (59 CIP-, 20 CIP+) were included. CIP+ patients had a 21.7% lower pretreatment FEV1pp compared with the CIP- group (95% confidence interval: -38.6 to -4.7). No statistically significant differences in FVCpp or FEV1/FVC were observed. The prevalence of obstructive lung disease was similar in both groups at 67% and 62% for the CIP+ and CIP- cohorts, as was the prevalence of current/former smoking at 100% and 93%, respectively. CONCLUSIONS: Pretherapy differences in lung function were evident between patients who did and did not develop CIP, though the prevalence of obstructive lung disease was similar. Prospective studies are needed to validate these findings, inform potential risk factors for CIP, and investigate the effects of ICI treatment and CIP on pulmonary function in patients with NSCLC.

ACR Appropriateness Criteria® Diffuse Lung Disease.

Diffuse lung disease, frequently referred to as interstitial lung disease, encompasses numerous disorders affecting the lung parenchyma. The potential etiologies of diffuse lung disease are broad with several hundred established clinical syndromes and pathologies currently identified. Imaging plays a critical role in diagnosis and follow-up of many of these diseases, although multidisciplinary discussion is the current standard for diagnosis of several DLDs. This document aims to establish guidelines for evaluation of diffuse lung diseases for 1) initial imaging of suspected diffuse lung disease, 2) initial imaging of suspected acute exacerbation or acute deterioration in cases of confirmed diffuse lung disease, and 3) clinically indicated routine follow-up of confirmed diffuse lung disease without acute deterioration. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

A scoping review of palliative care outcome measures in interstitial lung disease.

Interstitial lung disease (ILD) confers a high mortality and symptom burden, substantially impacting quality of life. Studies evaluating palliative care in ILD are rapidly expanding. Uniform outcome measures are crucial to assessing the impact of palliative care in ILD. This scoping review evaluates existing outcome measures in general health-related quality of life (HRQoL), physical health, mental health, social health and advance care planning (ACP) domains in patients with ILD. Articles in English with quantitative assessment of at least one measure of general HRQoL, physical health, mental health, social health or ACP in patients with ILD were included. Searches across three databases yielded 3488 non-duplicate articles. 23 met eligibility criteria and included three randomised controlled trials (RCTs) or secondary analysis of an RCT (13%), three cross-sectional studies or secondary analysis of cross-sectional study (13%), one prospective study (4%) and 16 retrospective studies (70%). Among eligible articles, 25 distinct instruments were identified. Six studies assessed general HRQoL (26%), 16 assessed physical health (70%), 11 assessed mental health (48%), six assessed social health (26%) and 16 assessed ACP (70%). The ability to compare results across studies remains challenging given the heterogeneity in outcome measures. Future work is needed to develop core palliative care outcome measures in ILD.

Patient-centered Outcomes Research in Interstitial Lung Disease: An Official American Thoracic Society Research Statement.

Background: In the past two decades, many advances have been made to our understanding of interstitial lung disease (ILD) and the way we approach its treatment. Despite this, many questions remain unanswered, particularly those related to how the disease and its therapies impact outcomes that are most important to patients. There is currently a lack of guidance on how to best define and incorporate these patient-centered outcomes in ILD research. Objectives: To summarize the current state of patient-centered outcomes research in ILD, identify gaps in knowledge and research, and highlight opportunities and methods for future patient-centered research agendas in ILD. Methods: An international interdisciplinary group of experts was assembled. The group identified top patient-centered outcomes in ILD, reviewed available literature for each outcome, highlighted important discoveries and knowledge gaps, and formulated research recommendations. Results: The committee identified seven themes around patient-centered outcomes as the focus of the statement. After a review of the literature and expert committee discussion, we developed 28 research recommendations. Conclusions: Patient-centered outcomes are key to ascertaining whether and how ILD and interventions used to treat it affect the way patients feel and function in their daily lives. Ample opportunities exist to conduct additional work dedicated to elevating and incorporating patient-centered outcomes in ILD research.