AB0620 EFFECTIVENESS OF RITUXIMAB IN PATIENTS WITH EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS. A MULTICENTER ANALYSIS.

Background:Rituximab (RTX) is effective in improving skin affection in patients with diffuse cutaneous systemic sclerosis (DcSSc). However, there are few data on early use of this drug.Objectives:To evaluate RTX effectiveness for skin disease in patients with DcSSc of less than 3 years of evolution.Methods:Multicenter, observational and retrospective study. Patients with DcSSc starting RTX within 3 years since first non-Raynaud symptom were recruited. Demographic variables, time of disease duration at the beginning of RTX, immune pattern and time on RTX treatment were collected. Effectiveness was defined as modified Rodnan skin score (mRSS) improvement. Evaluations were done by the same experienced rheumatologist. Patients subjective perception of skin hardening and/or tightness was evaluated. mRSS changes from baseline to 6 and 12 months after RTX beginning and, later on, to the last available observation were analysed using Wilcoxon test. Statistical analysis was performed with SPSS 20.0.Results:11 patients (8 women) were recruited from 2 university hospitals. Median age was 48 years (IQR 22). Median time since diagnosis to RTX beginning was 12 months (IQR 8). 5, 3 and 2 patients presented ATA +, RNPIII + and Ro-52 +, respectively. Median duration of RTX treatment was 12 months (IQR 68). Median baseline mRSS was 15.5 (IQR 18). Median mRSS after 6 and 12 months of RTX treatment and at last available mRSS evaluation was 15 (IQR 13), 14.5 (IQR 13) and 11 (IQR 16), respectively. mRSS showed statistically significant improvement at 6 (29%, IQR 37) and 12 months of RTX treatment (35%, IQR 34) and, thereafter, at last available observation (39%, IQR 51), compared to basal mRSS. Most patients reported subjective improvement at 6 (9 of 10 patients) and 12 months (6 of 7), and at last available evaluation (6 of 8); all other patients reported stability.Conclusion:In our experience, patients with DcSSc seem to benefit of early RTX treatment. Improvement may be seen as early as 6 months and seems to reach a plateau at 12 months.Disclosure of Interests:I Vázquez-Gómez: None declared, J. Narváez: None declared, J Lluch Pons: None declared, Marta Aguilar-Zamora: None declared, L Montolio-Chiva: None declared, Ana V Orenes Vera: None declared, Eduardo Flores: None declared, Elia Valls-Pascual Grant/research support from: Roche, Novartis, and AbbVie, Speakers bureau: AbbVie, Lilly, Pfizer, MSD, Novartis, Janssen, Bristol Myers Squibb, UCB Pharma, Desamparados Ybañez: None declared, À Martínez-Ferrer: None declared, A Sendra-García: None declared, Inmaculada Torner Hernández: None declared, V Núñez-Monje: None declared, Juanjo J Alegre-Sancho Consultant of: UCB, Roche, Sanofi, Boehringer, Celltrion, Paid instructor for: GSK, Speakers bureau: MSD, GSK, Lilly, Sanofi, Roche, UCB, Actelion, Pfizer, Abbvie, Novartis

Download Full-text

Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-217840 ◽

2020 ◽

pp. annrheumdis-2020-217840 ◽

Cited By ~ 1

Author(s):

Kimberly Showalter ◽

Robert Spiera ◽

Cynthia Magro ◽

Phaedra Agius ◽

Viktor Martyanov ◽

...

Keyword(s):

Gene Expression ◽

Machine Learning ◽

Systemic Sclerosis ◽

Clinical Improvement ◽

Smooth Muscle Actin ◽

Clinical Severity ◽

Support Vector ◽

Alpha Smooth Muscle Actin ◽

Modified Rodnan Skin Score ◽

Diffuse Cutaneous Systemic Sclerosis

ObjectiveWe sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma).MethodsFifty-eight forearm biopsies were evaluated from 26 individuals with dcSSc in two clinical trials. Histologic/immunophenotypic assessments of global severity, alpha-smooth muscle actin (aSMA), CD34, collagen, inflammatory infiltrate, follicles and thickness were compared with gene expression and clinical data. Support vector machine learning was performed using scleroderma gene expression subset (normal-like, fibroproliferative, inflammatory) as classifiers and histology scores as inputs. Comparison of w-vector mean absolute weights was used to identify histologic features most predictive of gene expression subset. We then tested for differential gene expression according to histologic severity and compared those with clinical improvement (according to the Combined Response Index in Systemic Sclerosis).ResultsaSMA was highest and CD34 lowest in samples with highest local Modified Rodnan Skin Score. CD34 and aSMA changed significantly from baseline to 52 weeks in clinical improvers. CD34 and aSMA were the strongest predictors of gene expression subset, with highest CD34 staining in the normal-like subset (p<0.001) and highest aSMA staining in the inflammatory subset (p=0.016). Analysis of gene expression according to CD34 and aSMA binarised scores identified a 47-gene fibroblast polarisation signature that decreases over time only in improvers (vs non-improvers). Pathway analysis of these genes identified gene expression signatures of inflammatory fibroblasts.ConclusionCD34 and aSMA stains describe distinct fibroblast polarisation states, are associated with gene expression subsets and clinical assessments, and may be useful biomarkers of clinical severity and improvement in dcSSc.

Download Full-text

Marked Improvement of Skin Involvement in Severe Progressive Systemic Sclerosis after Transplantation of Mesenchymal Stem Cells from an Allogeneic Haploidentical Related Donor.

Blood ◽

10.1182/blood.v110.11.4865.4865 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4865-4865

Author(s):

Maximilian Christopeit ◽

Marit Schendel ◽

Lutz Peter Mueller ◽

Gernot Keyszer ◽

Gerhard Behre

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Systemic Sclerosis ◽

Renal Involvement ◽

Progressive Systemic Sclerosis ◽

In Vitro Expansion ◽

Modified Rodnan Skin Score ◽

Diffuse Cutaneous Systemic Sclerosis ◽

Related Donor

Abstract Introduction. Mesenchymal stem cells (MSC) show immunosuppressive capacity in an allogeneic host. Severe progressive systemic sclerosis (SSc) is an autoimmune disease in which prognosis is worsened in individuals presenting with diffuse cutaneous, lung and renal involvement. Immunosuppression can improve the course of the disease. Methods. We transplanted a 41 year old female patient suffering from diffuse cutaneous systemic sclerosis with MSC from her father after in vitro expansion of the MSC. Results. The patient presented with a remarkable clinical response. Her ulcer surface decreased, the 17 Site Modified Rodnan Skin Score, vascular ultrasound, mouth aperture, the Visual Analogue Scale for pain (VAS), the Valentini Activity Score and the Hannover Functional Questionnaire showed encouraging improvements. The patient did not experience any adverse events during the first 300 days after transplantation. Conclusions. The transplantation of MSC from a haploidentical donor into a patient with systemic sclerosis is feasible, safe and effective. Furthermore is the transplantation of MSC from a haploidentical donor into an adult without severe pharmacological immunosuppression at the time of transplantation feasible and safe.

Download Full-text

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): randomised, double-blind, placebo-controlled multicentre trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-216823 ◽

2020 ◽

Vol 79 (5) ◽

pp. 618-625 ◽

Cited By ~ 7

Author(s):

Dinesh Khanna ◽

Yannick Allanore ◽

Christopher P Denton ◽

Masataka Kuwana ◽

Marco Matucci-Cerinic ◽

...

Keyword(s):

Systemic Sclerosis ◽

Vital Capacity ◽

Double Blind ◽

Double Blind Placebo ◽

Potential Efficacy ◽

Condition Score ◽

Modified Rodnan Skin Score ◽

Diffuse Cutaneous Systemic Sclerosis ◽

Pulmonary Arterial ◽

Safety Assessments

ObjectivesRiociguat is approved for pulmonary arterial hypertension and has antiproliferative, anti-inflammatory and antifibrotic effects in animal models of tissue fibrosis. We evaluated the efficacy and safety of riociguat in patients with early diffuse cutaneous systemic sclerosis (dcSSc) at high risk of skin fibrosis progression.MethodsIn this randomised, double-blind, placebo-controlled, phase IIb trial, adults with dcSSc of <18 months' duration and a modified Rodnan skin score (mRSS) 10–22 units received riociguat 0.5 mg to 2.5 mg orally three times daily (n=60) or placebo (n=61). The primary endpoint was change in mRSS from baseline to week 52.ResultsAt week 52, change from baseline in mRSS units was –2.09±5.66 (n=57) with riociguat and –0.77±8.24 (n=52) with placebo (difference of least squares means –2.34 (95% CI –4.99 to 0.30; p=0.08)). In patients with interstitial lung disease, forced vital capacity declined by 2.7% with riociguat and 7.6% with placebo. At week 14, average Raynaud’s condition score had improved ≥50% in 19 (41.3%)/46 patients with riociguat and 13 (26.0%)/50 patients with placebo. Safety assessments showed no new signals with riociguat and no treatment-related deaths.ConclusionsRiociguat did not significantly benefit mRSS versus placebo at the predefined p<0.05. Secondary and exploratory analyses showed potential efficacy signals that should be tested in further trials. Riociguat was well tolerated.

Download Full-text

Reliability and Validity of the Tender and Swollen Joint Counts and the Modified Rodnan Skin Score in Early Diffuse Cutaneous Systemic Sclerosis: Analysis from the Prospective Registry of Early Systemic Sclerosis Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.160654 ◽

2017 ◽

Vol 44 (6) ◽

pp. 791-794 ◽

Cited By ~ 7

Author(s):

Jessica K. Gordon ◽

Gandikota Girish ◽

Veronica J. Berrocal ◽

Meng Zhang ◽

Christopher Hatzis ◽

...

Keyword(s):

Systemic Sclerosis ◽

Content Validity ◽

Reliability And Validity ◽

Intraobserver Reliability ◽

Musculoskeletal Ultrasound ◽

Skin Score ◽

Modified Rodnan Skin Score ◽

Diffuse Cutaneous Systemic Sclerosis ◽

Early Systemic Sclerosis

Objective.To determine the inter/intraobserver reliability of the tender and swollen joint counts (TJC, SJC) and the modified Rodnan Skin Score (mRSS) in diffuse cutaneous systemic sclerosis (dcSSc) and to assess content validity of the TJC/SJC.Methods.Ten rheumatologists completed the SJC, TJC, and mRSS on 7 patients. Musculoskeletal ultrasound (MSUS) was performed.Results.Interobserver and intraobserver reliability for the TJC was 0.97 and 0.99, for the SJC was 0.24 and 0.71, and for the mRSS was 0.81 and 0.94, respectively. MSUS abnormalities did not correspond with SJC/TJC.Conclusion.We demonstrate excellent inter- and intraobserver reliability for the mRSS and TJC in dcSSc. However, the SJC and TJC did not correspond to MSUS.

Download Full-text

Circulating levels of active transforming growth factor β1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score

Rheumatology ◽

10.1093/rheumatology/kei088 ◽

2005 ◽

Vol 44 (12) ◽

pp. 1518-1524 ◽

Cited By ~ 36

Author(s):

M. Dziadzio ◽

R. E. Smith ◽

D. J. Abraham ◽

C. M. Black ◽

C. P. Denton

Keyword(s):

Systemic Sclerosis ◽

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Skin Score ◽

Modified Rodnan Skin Score ◽

Diffuse Cutaneous Systemic Sclerosis ◽

Circulating Levels

Download Full-text

Immunosuppression use in early systemic sclerosis may be increasing over time

Journal of Scleroderma and Related Disorders ◽

10.1177/23971983211000971 ◽

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.

Download Full-text

OP0339 Identification of a transcriptomic signature correlated with modified rodnan skin score (MRSS) in patients with diffuse cutaneous systemic sclerosis

10.1136/annrheumdis-2017-eular.5827 ◽

2017 ◽

Author(s):

I Agueusop ◽

S Illiano ◽

C Rocher ◽

E Boitier ◽

J Murphy ◽

...

Keyword(s):

Systemic Sclerosis ◽

Skin Score ◽

Transcriptomic Signature ◽

Modified Rodnan Skin Score ◽

Diffuse Cutaneous Systemic Sclerosis

Download Full-text

New composite endpoint in early diffuse cutaneous systemic sclerosis: revisiting the provisional American College of Rheumatology Composite Response Index in Systemic Sclerosis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-219100 ◽

2020 ◽

pp. annrheumdis-2020-219100

Author(s):

Dinesh Khanna ◽

Suiyuan Huang ◽

Celia J F Lin ◽

Cathie Spino

Keyword(s):

Systemic Sclerosis ◽

Health Assessment ◽

Composite Endpoint ◽

Response Index ◽

American College Of Rheumatology ◽

Core Set ◽

Weighted Score ◽

Modified Rodnan Skin Score ◽

Diffuse Cutaneous Systemic Sclerosis ◽

Composite Response

ObjectivesAmerican College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS) is a composite endpoint to assess the likelihood of improvement in diffuse systemic sclerosis. ACR-CRISS is a weighted score and includes five core set measures: modified Rodnan skin score, FVC% predicted, health assessment questionnaire–disability index, and patient and clinician global assessments.MethodsWe analysed core set measures from 354 participants who participated in three placebo-controlled trials. We generated 10 development datasets, randomly selected from 2/3 of the participants, stratified by study and treatment group. The remaining participants (1/3 of the participants) formed the validation sets. Risk differences (RDs) between active and placebo treatments were calculated by averaging over the replicate datasets; bootstrap 95% CIs for the RDs to estimate the magnitude of treatment effects.ResultsIn the development sets (n=237), the proportion of participants in the active group had statistically higher improvement in >1 of 5 core set measures versus the placebo group. For example, the proportion who improved by ≥20% in ≥3 core set measures was 49.4% in the active versus338.9% in the placebo; RD: 10.5%, 95% CI4.9 % to 16.1%. In the validation sets (n=117), the proportion who improved by ≥20% in ≥3 core set measures was 50.3% in the active versus35.63% in the placebo (RD:114.8%, 95% CI 3.1% to225.7%). Similar trends were seen with larger percentage cut-offs.ConclusionRevised CRISS, as assessed by the proportion of participants who improved by a certain percentage in ≥3 of 5 core set measures, is a potential new composite outcome measure.

Download Full-text