Lesley Ann Saketkoo

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study.

AbstractAnti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.

International Classification of Functioning, Disability and Health Core Set construction in systemic sclerosis and other rheumatic diseases: a EUSTAR initiative

OBJECTIVES To outline rationale and potential strategies for rheumatology experts to be able to develop disease-specific Core Sets under the framework of the International Classification of Functioning, Disability and Health (ICF). ICF is a universal framework introduced by the World Health Organization (WHO) to describe and quantify the impact and burden on functioning of health conditions associated with impairment/disability. METHODS A combined effort of the EULAR Scleroderma Clinical Trial and Research and the ICF Research Branch was initiated to develop an ICF language for scleroderma. From our Medline literature review, using the abbreviation and spelled out version of ICF, we assembled approaches and methodological reasoning for steps of core set development. RESULTS The ICF can be used for patient care and policy-making, as well as the provision of resources, services and funding. The ICF is used on institutional, regional, national and global levels. Several diseases now have ICF Core Sets. Patients with complex rheumatologic diseases will benefit from a disease-specific ICF Core Set and should be included in all stages of development. ICF Core Set development for rheumatic diseases can be conducted from a number of feasible strategies. CONCLUSION This overview should help to clarify useful processes leading to development of an ICF Core Set, and also provide a platform for expert groups considering such an endeavour.

Biologic therapies in the treatment of sarcoidosis

ABSTRACT Sarcoidosis is a disease of remarkable heterogeneity in organ manifestation, severity and natural history, characterized by the presence of non-caseating granulomas. The majority of cases are acute and self-limited or remit with short courses of glucocorticoids; however, a proportion progress to a life-threatening obliterative fibrotic type associated with significant disability related to pulmonary, cardiac, ocular or central nervous system involvement. Biologic agents have been demonstrated in the successful treatment of refractory organ-threatening sarcoidosis; and though sarcoidosis remains elusive in predictability of progression, strong evidence suggests an indisputably efficacious role for these agents in efforts to stave morbidity and mortality related to sarcoidosis. This paper provides a review of sarcoidosis mechanistic etiopathogenesis to highlight the hypothetical underpinnings of the utility and concerns of current biologic treatments in current use and the potential future applications of newer agents and those under development.

Clinical characteristics and survival of systemic sclerosis patients with pulmonary hypertension and elevated wedge pressure: Observations from the PHAROS cohort

Systemic sclerosis (SSc) is a complex autoimmune disease commonly associated with pulmonary hypertension (PH). When associated with elevated pulmonary artery wedge pressure (PAWP), pulmonary artery pressure (PAP) is either in‐proportion (post‐capillary PH) or higher than expected (combined PH) relative to the increased PAWP.

SAT0442 Mycophenolate Mofetil (MMF) Use in Scleroderma Patients with Pulmonary Hypertension: FVC, Outcomes and Survival- Observations from the Pulmonary Hypertension Recognition and Outcomes in Scleroderma (Pharos) Cohort

Background Systemic sclerosis (SSc) related pulmonary hypertension (PH) carries a high mortality and patients with SSc-PH related to restrictive lung disease (RLD) having an even worse prognosis. Speculation regarding the potential of MMF to exert anti-fibrotic and anti-remodeling effects on parenchymal lung and vascular intimal fibrosis, led us to query the possible differences in outcomes and survival between 4 groups based on forced vital capacity (FVC) and MMF use in SSc PH. Methods PHAROS is a prospective registry designed to provide substantive data to recognize aspects of PH unique to SSc. For this analysis patients were stratified by an FVC of >70% or ≤70% predicted on spirometry at the time of PH diagnosis by right heart catheterization (RHC) and then by MMF duration of ≥6 months from PH diagnosis. MMF<6 months or cyclophosphamide use was exclusionary to all groups. Calculations are derived from one-way ANOVA with Tukeys post test or Kruskal Wallis with Dunns post-test. Categorical variables were compared with Chi square. These analyses were followed by Cox and stepwise backward regression analysis to assess baseline characteristics associated with risk of death (variables with p<0.1 included) and Kaplan-Meyer analysis. Results 256 cases from the PHAROS database matched criteria and had baseline spirometry results coincident with diagnostic RHC, of those 173 had a baseline FVC>70% with 23 on MMF and 150 without; and 83 had a baseline FVC≤70% with 26 on MMF and 57 without. Across groups, no differences were found in age, disease duration, race nor surprisingly in skin score, 6 minute walk test (6MWD) or NYHA Class. WHO Group I, female sex and lcSSc classification were higher in the FVC>70 MMF- group; with FVC≤70%/RLD groups having significantly more lung fibrosis, lower FVC:DLCO ratio, and more WHO Group III classifications supporting our RLD definition. There was no significant interval change in baseline FVC and follow-up FVC 6-18 month later. Of interest, baseline mPAP and PVR were lower in both MMF+ groups regardless of FVC. Survival was statistically worse with FVC≤70 without MMF at 3 years (p=0.04). Male sex, mPAP, DLCO were significant independent predictors of death in all groups (p=0.001, p<0.0001, p<0.0001) especially when FVC was ≤70% (p=0.007, p=0.003, p=0.005). Conclusions Statistically significant improved survival in patients with PH with FVC≤70 treated with MMF even in the absence of improvement of FVC is intriguing. MMF effects on pulmonary artery remodeling should be considered. These findings warrant prospective controlled investigations and examination of larger combined international databases of MMF in SScPH particularly in those with restrictive lung disease. Acknowledgements PHAROS is supported by an investigator initiated grant from Gilead Science. Disclosure of Interest L. A. Saketkoo Grant/research support from: ACR/EULAR Exchange Awardee; Gilead, M. Lammi: None declared, A. Fischer: None declared, J. Molitor: None declared, V. Steen Grant/research support from: Actelion Pharmaceuticals US Bayer CSL Berhing Intermune Roche Pharmaceuticals Sanofi-Aventis Pharmaceutical UCB United Therapeutics

There is a need for new systemic sclerosis subset criteria. A content analytic approach

Objectives. Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. Methods. We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. Results. Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). Conclusions. We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

Association Between Initial Oral Therapy and Outcomes in Systemic Sclerosis-Related Pulmonary Arterial Hypertension.

To compare time to clinical worsening (TTCW) based on initial oral therapy for pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc)–related PAH.

Association between Initial Oral Therapy and Outcomes in Systemic Sclerosis‐related Pulmonary Arterial Hypertension: Observations from PHAROS

To compare time to clinical worsening (TTCW) based on initial oral therapy for pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc)–related PAH.

Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database

Abstract Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort). African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987–2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses. The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynauds phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ⩽50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort. Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry.

Physical activity and training in sarcoidosis: review and experience-based recommendations

ABSTRACT Introduction: Sarcoidosis is a multisystemic inflammatory disorder with a great variety of symptoms, including fatigue, dyspnea, pain, reduced exercise tolerance and muscle strength. Physical training has the potential to improve exercise capacity and muscle strength, and reduce fatigue. The aim of this review and survey was to present information about the role of physical training in sarcoidosis and offer practical guidelines. Areas covered: A systematic literature review guided an international consensus effort among sarcoidosis experts to establish practice-basic recommendations for the implementation of exercise as treatment for patients with various manifestations of sarcoidosis. International sarcoidosis experts suggested considering physical training in symptomatic patients with sarcoidosis. Expert commentary: There is promising evidence of a positive effect of physical training. Recommendations were based on available data and expert consensus. However, the heterogeneity of these patients will require modification and program adjustment of the standard rehabilitation format for e.g. COPD or interstitial lung diseases. An optimal training program (types of exercise, intensities, frequency, duration) still needs to be defined to optimize training adjustments, especially reduction of fatigue. Further randomized controlled trials are needed to consolidate these findings and optimize the comprehensive care of sarcoidosis patients.