Treatment of systemic sclerosis associated ILD: Lessons from clinical trials

Systemic sclerosis–associated interstitial lung disease remains a leading cause of mortality. Despite decades of clinical trials, the treatment effects of disease modifying anti-rheumatic drugs continue to be modest and there remains a great need for therapies that attenuate and hopefully ameliorate parenchymal lung disease. In this review, we highlight the key clinical trials that have shaped the management strategies employed by the authors, providing their strength of recommendation based on level of evidence. We also review lessons learned in more recent years, suggesting a benefit in targeting patients with subclinical interstitial lung disease with high risk for progression early in the disease course, as well as the benefit seen in a large clinical trial leading to the first Food and Drug Administration–approved treatment for systemic sclerosis–associated interstitial lung disease. These lessons come in a context of heterogeneity of patient populations and response to therapy, as well as the inherent constraints of time-limited studies to detect meaningful outcomes for patients

Tocilizumab Prevents Progression of Early Systemic Sclerosis Associated Interstitial Lung Disease

OBJECTIVE: Tocilizumab has demonstrated lung function preservation in two randomized controlled trials in early systemic sclerosis (SSc). This effect has yet to be characterized in terms of quantitative radiographic lung involvement. In this post-hoc analysis, we assess tocilizumab's impact on lung function preservation, stratifying treatment arms by the degree of radiographic lung involvement. METHODS: The focuSSced trial was a phase 3, randomized placebo-controlled trial of tocilizumab in patients with SSc and progressive skin disease. Participants had baseline and serial spirometry along with high resolution chest CT at baseline and week 48. Quantitative interstitial lung disease and fibrosis were derived using computer software. We divided quantitative interstitial lung disease in mild (5-10%), moderate (>10-20%), or severe (>20%) categories. RESULTS: Of 210 participants recruited in the trial, 136 [65%] had interstitial lung disease. The majority of these participants had moderate-to-severe involvement defined by >10% lung involvement (77%). The tocilizumab arm demonstrated preservation of forced vital capacity over 48 weeks (least squared mean change in %predicted = -0.1) compared to placebo (-6.3%). For mild, moderate, and severe QILD, the mean decline in the %pFVC in the tocilizumab arm at 48 weeks were -4.1, 0.7, and 2.1, and in the placebo group were -10.0, -5.7, and -6.7, respectively. Similar treatment-related preservation findings were seen independent of fibrosis severity. CONCLUSION: Tocilizumab in early SSc- associated interstitial lung disease with progressive skin disease stabilized forced vital capacity over 48 weeks, independent of the extent of quantitative radiographic interstitial lung disease or fibrosis

Systemic Sclerosis–Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration–Approved Therapies in Clinical Practice

Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the Food & Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-ILD: nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, two generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a Phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy in the management of patients with SSc-ILD is still to be determined. The objectives of this review are two-fold: (1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and (2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical vs. clinical ILD) and associated risk of progression (low vs. high risk). The pharmacological and non-pharmacological options as first and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD

Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: a scoping review protocol

Introduction: Limited cutaneous systemic sclerosis (lcSSc) is the most frequent subset of systemic sclerosis. Despite this, lcSSc is not the major focus of clinical studies. The lack of interventional studies in lcSSc is due, in part, to a paucity of relevant outcome measures to effectively evaluate this subset. A combined response index dedicated to lcSSc would facilitate development of well-designed trials and approval of new drugs. The objective of this scoping review is to perform a broad and comprehensive identification of the outcome measures (core set items) within relevant domains, which have been used so far to assess lcSSc. Methods and analysis: The planned scoping review will be based on the approach proposed by Arksey et al and further developed by Levac et al. Development and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews checklist and guidelines. The development of the search strategy was guided by the concepts of domains and outcomes based on the Outcome Measures in Rheumatology approach and by the different names and definitions of SSc, with a specific emphasis on their occurrence in clinical trial studies. Two databases will be searched: MEDLINE and Embase. Studies in English, published from the year 1988 onwards, will be included, since 1988 corresponds to the publication of LeRoy’s first consensus definition of lcSSc. Data will be extracted and analysed using a standardised charting tool. Ethics and dissemination: No ethical approval is required for this study. The results will be submitted to an international peer-reviewed journal and scientific conferences, informing the discussion on which items should be included in a combined response index dedicated to lcSSc (the CRISTAL project: Combined Response Index for Scleroderma Trial Assessing lcSSc)

Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes

Systemic sclerosis (systemic scleroderma) is characterized by a heterogeneous range of clinical manifestations. Systemic sclerosis is classified into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis subgroups based on the extent of skin involvement. Randomized controlled trials in scleroderma have mainly focused on diffuse cutaneous systemic sclerosis partly because the measurement of skin involvement, critical for evaluating a therapeutic intervention, is more dynamic in this subset. Nonetheless, limited cutaneous systemic sclerosis, the most common cutaneous subset (about two-third), is also associated with significant morbidity and detrimental impact on health-related quality of life. The lack of interventional studies in limited cutaneous systemic sclerosis is partly due to a lack of relevant outcome measures to evaluate this subgroup. Combining several clinically meaningful outcomes selected specifically for limited cutaneous systemic sclerosis may improve representativeness in clinical trials and responsiveness of outcomes measured in randomized controlled trials. A composite index dedicated to limited cutaneous systemic sclerosis combining such relevant outcomes could advance clinical trial development for limited cutaneous systemic sclerosis by providing the opportunity to test and select among candidate drugs that could act as disease-modifying treatments for this neglected subgroup of systemic sclerosis. This proposed index would include items selected by expert physicians and patients with limited cutaneous systemic sclerosis across domains grounded in the lived experience of limited cutaneous systemic sclerosis. This article reviews the reasons behind the relative neglect of limited cutaneous systemic sclerosis, discusses the current state of outcome measures for limited cutaneous systemic sclerosis, identifies challenges, and proposes a roadmap for a combined limited cutaneous systemic sclerosis-specific treatment response index

RISK FACTORS FOR LUNG FUNCTION DECLINE IN SYSTEMIC SCLEROSIS INTERSTITIAL LUNG DISEASE IN A LARGE SINGLE-CENTER COHORT

International audienc

Implementation of Hip Fracture Co‐Management Program ( AGS CoCare: Ortho®

© 2020 The American Geriatrics Society OBJECTIVES: Acute hip fracture is common and leads to significant morbidity and mortality. Co-management programs, such as American Geriatric Society (AGS) CoCare: Ortho®, that optimize perioperative care of older adults, have demonstrated improved outcomes. Yet there is substantial variation in hip fracture care nationally. Our objective was to describe the implementation of AGS CoCare: Ortho® across a large integrated health system. DESIGN: Program implementation of four phases. SETTING: Large integrated health system. PARTICIPANTS: One tertiary and three community hospitals. MEASUREMENTS: The first two phases were communication and system-level planning. The communication phase consisted of getting health system leadership buy-in, creating an interdisciplinary steering committee, and building a business model. The planning phase consisted of choosing process and outcome measures, ensuring accurate and timely data collection, and creating standardized order sets and physician documentation. RESULTS: The second two phases were hospital-level planning and implementation. The planning phase consisted of identifying sites and developing the co-management structure. The implementation phase consisted of identifying and engaging frontline Northwell Health, rolling out the program, optimizing workflow, and educating providers. CONCLUSION: The program was implemented at four diverse sites. Major lessons learned included the need for an engaged steering committee to oversee the program; the importance of standardizing order sets and documentation; the utilization of hospitalists as co-managers; the benefit of developing and actively using a data dashboard; the challenge of ensuring wide uptake of education modules; and the need to take proactive steps to improve multidisciplinary communication

Tocilizumab Prevents Progression of Early Systemic Sclerosis–Associated Interstitial Lung Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168321/1/art41668.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168321/2/art41668_am.pd

Implementation of Hip Fracture Co-Management Program (AGS CoCare: Ortho®) in a Large Health System

© 2020 The American Geriatrics Society OBJECTIVES: Acute hip fracture is common and leads to significant morbidity and mortality. Co-management programs, such as American Geriatric Society (AGS) CoCare: Ortho®, that optimize perioperative care of older adults, have demonstrated improved outcomes. Yet there is substantial variation in hip fracture care nationally. Our objective was to describe the implementation of AGS CoCare: Ortho® across a large integrated health system. DESIGN: Program implementation of four phases. SETTING: Large integrated health system. PARTICIPANTS: One tertiary and three community hospitals. MEASUREMENTS: The first two phases were communication and system-level planning. The communication phase consisted of getting health system leadership buy-in, creating an interdisciplinary steering committee, and building a business model. The planning phase consisted of choosing process and outcome measures, ensuring accurate and timely data collection, and creating standardized order sets and physician documentation. RESULTS: The second two phases were hospital-level planning and implementation. The planning phase consisted of identifying sites and developing the co-management structure. The implementation phase consisted of identifying and engaging frontline Northwell Health, rolling out the program, optimizing workflow, and educating providers. CONCLUSION: The program was implemented at four diverse sites. Major lessons learned included the need for an engaged steering committee to oversee the program; the importance of standardizing order sets and documentation; the utilization of hospitalists as co-managers; the benefit of developing and actively using a data dashboard; the challenge of ensuring wide uptake of education modules; and the need to take proactive steps to improve multidisciplinary communication

Systemic Sclerosis–Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration–Approved Therapies in Clinical Practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171184/1/art41933_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171184/2/art41933.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171184/3/art41933-sup-0001-Disclosureform.pd