scholarly journals Nintedanib in patients with systemic sclerosis‐associated interstitial lung disease: subgroup analyses by autoantibody status and skin score

2021 ◽  
Author(s):  
Masataka Kuwana ◽  
Yannick Allanore ◽  
Christopher P Denton ◽  
Jörg HW Distler ◽  
Virginia Steen ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Skin Score ◽  
Subgroup Analyses ◽  
Autoantibody Status

Immunosuppression use in early systemic sclerosis may be increasing over time

2021 ◽  
pp. 239719832110009
Author(s):  
Ryan Park ◽  
Tatiana Nevskaya ◽  
Murray Baron ◽  
Janet E Pope
Keyword(s):  
Mycophenolate Mofetil ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Immunosuppressive Therapy ◽  
Skin Score ◽  
The Past ◽  
Modified Rodnan Skin Score ◽  
Diffuse Cutaneous Systemic Sclerosis ◽  
Early Systemic Sclerosis

Background: Immunosuppression remains the main treatment for progressing skin involvement, interstitial lung disease and inflammatory joint or muscle disease in systemic sclerosis. This study investigated the pattern and trends in immunosuppressive agents used in early systemic sclerosis (diagnosed before and after 2007) to determine whether the changes in the preferred type, timing and combination of immunosuppression took place over the past decade. Methods: In total, 397 Canadian Scleroderma Research Group database patients (183 diffuse cutaneous systemic sclerosis and 214 limited cutaneous systemic sclerosis) who had baseline and follow-up visits within 3 years (mean: 1.8 ± 0.8) after disease onset were included: 82% females, age at diagnosis 53 ± 13 years. Bivariate, chi-square, analysis of variance and adjusted regression analyses were used. Results: In total, 115 diffuse cutaneous systemic sclerosis patients (63%) and 62 limited cutaneous systemic sclerosis (29%) received immunosuppressive drugs, most commonly methotrexate, followed by mycophenolate mofetil and cyclophosphamide. In diffuse cutaneous systemic sclerosis, immunosuppressants were prescribed after 2007 more often (74% vs 50%, p = 0.001), especially methotrexate ( p = 0.02) and mycophenolate mofetil ( p = 0.04), and earlier (peak at 2 years after onset). Immunosuppressive therapy was associated with male gender, interstitial lung disease, anti-Scl70 positivity, ACA negativity and inflammatory joint disease in limited cutaneous systemic sclerosis and with ACA negativity and a higher modified Rodnan skin score in diffuse cutaneous systemic sclerosis. Multivariate regression analysis showed that the use of immunosuppressants after 2007 was predicted only by ACA negativity in limited cutaneous systemic sclerosis and by younger age in diffuse cutaneous systemic sclerosis. Conclusion: Over the past decade, there has been a trend to prescribe immunosuppressants more often and earlier in diffuse cutaneous systemic sclerosis patients, regardless of modified Rodnan skin score. Methotrexate is being more frequently used, and mycophenolate mofetil has gained favour over cyclophosphamide. Autoantibody status was the most consistent predictor of immunosuppressive therapy.

scholarly journals Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts

2018 ◽  
Vol 78 (1) ◽  
pp. 122-130 ◽  
Author(s):  
Elizabeth R Volkmann ◽  
Donald P Tashkin ◽  
Myung Sim ◽  
Ning Li ◽  
Ellen Goldmuntz ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cox Model ◽  
Short Term ◽  
Term Survival ◽  
Skin Score ◽  
Increased Risk ◽  
Significant Difference

ObjectiveTo assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II.MethodsSLS I randomised 158 patients with SSc-ILD to 1  year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling.ResultsAfter a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data.ConclusionIn addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.

scholarly journals P149 Haematopoietic stem cell transplantation in systemic sclerosis: Sheffield Teaching Hospitals’ experience

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Ruth Smith ◽  
John Snowden ◽  
Mohammed Akil
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Stem Cell Transplantation ◽  
Lung Disease ◽  
Effective Treatment ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
Skin Score

Abstract Background Haematopoietic stem cell transplantation (HSCT) was first used as a treatment for systemic sclerosis (SSc) in the 1990s. By April 2018 the European Society for Blood and Bone Marrow Transplantation had 533 cases on its registry. Sheffield is the main UK centre for HSCT for SSc with 6 people having undergone the procedure since 2007. HSCT works by rebooting the immune system. Autoreactive T cells are suppressed by proliferation of regulatory T cells and improvement in T cell receptor diversity. Autologous HSCT has been shown to be an effective treatment for SSc, and has been compared to monthly pulsed intravenous cyclophosphamide in the ASSIST, ASTIS and SCOT trials. HSCT showed greater improvement in respiratory and cutaneous disease (ASSIST) and produced a superior global rank composite score based on a hierarchy of disease features (SCOT) compared with cyclophosphamide. However, although there was longer term survival benefit compared with cyclophosphamide, treatment related mortality (TRM) was high at 10% (ASTIS). TRM was attributed to SSc-related cardio-pulmonary dysfunction, and therefore patient selection for HSCT is important and all must undergo a thorough cardio-pulmonary evaluation to mitigate risk. Methods We performed a retrospective review of the characteristics and outcomes of patients who have undergone HSCT for SSc in Sheffield. Results Legend Symptom s R Raynaud’s; DU digital ulcers; dSSc diffuse systemic sclerosis; ILD interstitial lung disease; P pericarditis; M myositis; GAVE gastric antral vascular ectasia; SRC scleroderma renal crisis. Previous treatments: MTX methotrexate; MMF mycophenolate; CYA cyclosporine; CYCLO cyclophosphamide; AZA azathioprine; HCQ hydroxychloroquine mRSS modified Rodnan skin score Conclusion Patient numbers are small and follow-up is limited to 12 years, but the procedure has been well tolerated and improved patients’ skin score, with the exception of patient 6. His pre-procedure screening tests showed no evidence of interstitial lung disease, pulmonary artery hypertension or left ventricular dysfunction. The cause of his acute deterioration is unclear but acute campylobacter myocarditis or cyclophosphamide cardiac toxicity have been postulated. Sheffield’s experience has shown HSCT to be an effective treatment for SSc, but one that is not without risk. Disclosures R. Smith None. J. Snowden Other; Speaker fees at educational events supported by Janssen, Jazz, Mallinckrodt & Gilead. Member of a trial IDMC for Kiadis Pharma. Chairs NHS England Clinical Reference Group for Blood & Marrow Transplan. M. Akil Honoraria; AbbVie, Actelion, Celgene, Astra Zenica, Lilly and UCB.

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