AB0431 EXPLORING THE UTILITY OF THE AMERICAN COLLEGE OF RHEUMATOLOGY (ACR) CRISS IN PATIENTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS

Background:The ACR Composite Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) was developed to measure the probability of improvement in response to treatment in patients with early diffuse cutaneous SSc (dcSSc), accounting for new/worsening cardiopulmonary involvement and/or renal crisis, and changes in modified Rodnan skin score, forced vital capacity, health assessment questionnaire disability index, and patient’s and physician’s global impressions. In patients with SSc-ILD, treatment response may be reflected as slower progression, stabilisation or improvement.Objectives:Using data from patients with dcSSc and ILD in the placebo group of the SENSCIS trial, we analysed the probability of improvement using the ACR CRISS score at week 52. We also evaluated whether the CRISS numerator could provide information on the spectrum of responses in this patient population.Methods:The SENSCIS trial enrolled subjects with SSc-ILD with onset of first non-Raynaud symptom ≤7 years before screening, FVC ≥40% predicted, and fibrotic ILD ≥10% extent on an HRCT scan. Subjects on prednisone ≤10 mg/day (or equivalent) and/or stable therapy with mycophenolate or methotrexate were allowed to participate. Subjects were randomised to receive nintedanib or placebo. Subjects were not randomised by use of mycophenolate. In patients randomised to receive placebo who had dcSSc and/or mRSS >15 at baseline, we analysed the ACR CRISS and its numerator at week 52 in subgroups by use of mycophenolate at baseline. Analyses were exploratory and descriptive.Results:Of 117 analysed subjects in the placebo group who had dcSSc and/or mRSS >15 at baseline, 60 (51.3%) were taking mycophenolate at baseline. Compared with patients not taking mycophenolate at baseline, those taking mycophenolate had a lower mean age (48.4 [SD 11.8] vs 53.1 [13.4] years), lower mean FVC % predicted (68.8 [17.0] vs 73.0 [14.6]), and a greater proportion were female (76.7% vs 71.9%); median time since first onset of non-Raynaud symptom was similar (3.9 vs 4.5 years, respectively) as was mean (SD) mRSS (16.5 [7.7] vs 15.9 [8.0], respectively). One patient (taking mycophenolate at baseline) had limited cutaneous SSc. At week 52, median (Q1, Q3) ACR CRISS score was 0.036 (0.001, 0.601) in subjects taking mycophenolate and 0.002 (0.000, 0.112) in subjects not taking mycophenolate at baseline, and mean (SD) ACR CRISS score was 0.28 (0.37) in subjects taking mycophenolate and 0.16 (0.31) in subjects not taking mycophenolate at baseline (Figure 1). In these groups, respectively, 25.0% and 14.0% of subjects had CRISS score >0.6 (considered improved) at week 52. The CRISS numerator provided a broader distribution of response values, but was not informative in this patient population.Conclusion:In exploratory analyses, among subjects with dcSSc and ILD who received placebo in the SENSCIS trial, the proportion considered improved at week 52 based on ACR CRISS score was numerically greater in patients taking than not taking mycophenolate at baseline. There remains a need for composite scores that provide better interpretation of the magnitude of response in patients with SSc.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Francesco Del Galdo Speakers bureau: Actelion and AstraZeneca, Consultant of: Actelion, AstraZeneca, Boehringer Ingelheim, Capella BioScience, ChemomAb and Mitsubishi Tanabe Pharma, Grant/research support from: Capella BioScience, Kymab and Mitsubishi Tanabe Pharma, Oliver Distler Consultant of: AbbVie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Bayer, Blade Therapeutics, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Glenmark Pharmaceuticals, Horizon (Curzion) Pharmaceuticals, Inventiva, IQVIA, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Target Bioscience, Topadur Pharma and UCB, Grant/research support from: Kymera Therapeutics and Mitsubishi Tanabe Pharma, Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals, Daniel Wachtlin Employee of: Currently an employee of Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc.

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AB0436 OUTCOMES OF DOSE-REDUCTION OR DISCONTINUATION OF TOCILIZUMAB IN PATIENTS WITH EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2471 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1246.3-1247

Author(s):

Y. Isomura ◽

Y. Yamasaki ◽

Y. Shirai ◽

M. Kuwana

Keyword(s):

Systemic Sclerosis ◽

Dose Reduction ◽

Clinical Outcomes ◽

Inflammatory Markers ◽

Topoisomerase I ◽

Phase Iii ◽

Optimal Timing ◽

Skin Thickness ◽

Research Support ◽

Diffuse Cutaneous Systemic Sclerosis

Background:Potential efficacy and favorable safety profiles of tocilizumab (TCZ) have been demonstrated in patients with diffuse cutaneous systemic sclerosis (dcSSc) [1, 2]. However, clinical outcomes after dose-reduction or discontinuation of TCZ due to an improvement of skin thickness remain unclear.Objectives:To investigate the clinical outcomes after dose-reduction or discontinuation of TCZ in patients with dcSSc in a real-world setting.Methods:This is a single-center, retrospective, observational study using a database of consecutive SSc patients who visited our center between April 2014 and October 2020. For this study, we selected eligible patients from the database based on the following criteria: patients who (i) fulfilled the ACR/EULAR classification criteria, (ii) were classified as having dcSSc, (iii) had been treated with TCZ for at least 6 months, and (iv) were follow-up >6 months after TCZ introduction. Clinical information including demographic and clinical characteristics at TCZ introduction; dosing, administration route, and adherence of TCZ; and serial clinical parameters (modified Rondan total skin thickness score [mRSS], and percent predicted forced vital capacity [%FVC]), safety profiles, and outcomes after TCZ introduction regardless of TCZ continuation were extracted from the database.Results:Of 404 patients enrolled in the database, 13 dcSSc patients were eligible for this study. Baseline characteristics included a mean age of 51 ± 9 years, 85% female, disease duration of 27 ± 24 months, and mRSS of 19.5 ± 10.6. Seven patients (54%) had HRCT-confirmed ILD at baseline, and 9 (69%) were positive for anti-topoisomerase I antibody. Two (14%) and 11 (85%) were on mycophenolate mofetil and low-dose prednisolone (7.2 ± 6.0 mg/day), respectively. Seven patients (54%) each had active skin disease and elevated inflammatory markers defined in the phase III clinical trial [2], while only 4 (31%) fulfilled the inclusion criteria. TCZ was initially administered intravenously (8 mg/kg every 4 weeks) in 8 patients and subcutaneously in 5 (162 mg every 2 weeks in 4 and every week in one). At one year, mRSS was improved from 20.9 ± 11.4 to 10.7 ± 8.9 in 11 patients (p = 0.007), and %FVC was stable in 7 patients with ILD (76.8 ± 15.0 to 78.6 ± 16.1). During the observation period of 60.4 ± 26.7 months, 4 patients were treated with a stable dose of TCZ, while TCZ dose was reduced and/or discontinued in 9. Four of them discontinued TCZ due to adverse events (n = 2; acute lung injury and phlegmon) or prominent improvement of skin thickening (n = 2). Of 9 patients with dose reduction/discontinuation of TCZ, 4 patients who discontinued TCZ (n = 3) or received dose reduction of TCZ (n = 1) experienced a recurrence of progressive skin thickening together with inflammatory complications, including edematous induration of the skin, progression of ILD, polyarthritis, and/or pericarditis with increased inflammatory markers. The interval between dose-reduction/discontinuation of TCZ and clinical worsening ranged from 2 to 11 months. These manifestations were promptly improved by dose-escalation or resumption of TCZ in all patients except one who experienced progressive ILD and died of respiratory failure 27 months later.Conclusion:In dcSSc patients who experienced improvement of skin thickness during treatment with TCZ, dose-reduction or discontinuation of TCZ may result in a recurrence of the disease. Randomized comparative studies are necessary to examine optimal timing for dose-reduction or discontinuation of TCZ in dcSSc patients after improvement of skin thickness.References:[1]Khanna, D., et al., Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis, 2018. 77(2):212-220.[2]Khanna, D., et al., Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med, 2020; 8(10): 963-974.Disclosure of Interests:Yohei Isomura: None declared, Yoshioki Yamasaki Speakers bureau: Boehringer-Ingelheim, Nippon Shinyaku, Bristol Myers, Yuichiro Shirai Speakers bureau: Janssen, Grant/research support from: Janssen, Masataka Kuwana Speakers bureau: Abbie, Astellas, Asahi Kasei Parma, Boehringer-Ingelheim, Chugai, Eisai, Janssen, MBL, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Pfizer, Tanabe-Mitsubishi, Consultant of: Boehringer-Ingelheim, Chugai, Corbus, MBL, Mochida, Grant/research support from: Boehringer-Ingelheim, Chugai, Eisai, MBL, Ono Pharmaceuticals, Tanabe-Mitsubishi

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SAT0500 HOW THE ADULT CRISS WORKS IN PEDIATRIC jSSc PATIENTS - RESULTS FROM THE JUVENILE SCLERODERMA INCEPTION COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2298 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1206.2-1206

Author(s):

J. Klotsche ◽

I. Foeldvari ◽

O. Kasapcopur ◽

A. Adrovic ◽

K. Torok ◽

...

Keyword(s):

Systemic Sclerosis ◽

Area Under Curve ◽

Health Assessment ◽

Organ Damage ◽

Left Ventricular ◽

Inception Cohort ◽

Research Support ◽

Predicted Probability ◽

New Onset

Background:The Composite Response Index in Systemic Sclerosis (CRISS) was developed by Dinesh Khanna as a response measure in patients with adult systemic sclerosis. CRISS aims to capture the complexity of systemic sclerosis and to provide a sensitive measure for change in disease activity. The CRISS score is based on a two-step approach. First, significant disease worsening or new-onset organ damage is defined as non-responsiveness. In patients who did not fulfill the criteria of part one, a probability of improvement is calculated for each patient based the Rodnan Skin Score (mRSS), percent predicted forced vital capacity (FVC%), patient and physician global assessments (PGA), and the Health Assessment Questionnaire Disability Index (HAQ-DI). A probability of 0.6 or higher indicates improvement.Objectives:The objective of this study was to validate the CRISS in a prospectively followed cohort of patients with juvenile systemic sclerosis (jSSc).Methods:Data from the prospective international inception cohort for jSSc was used to validate the CRISS. Patients with an available 12-months follow-up were included in the analyses. Clinically improvement was defined by the anchor question about improvement (much better or little better versus almost the same, little worse or much worse) in patients overall health due to scleroderma since the last visit provided by the treating physician.Results:Forty seven jSSc patients were included in the analysis. 74.2% had diffuse subtype. The physician rated the disease as improved in 34 patients (72.3%) since the last visit. No patient had a renal crisis or new onset of left ventricular failure during the 12-months follow-up. Three patients (3.4%) each had a new onset or worsening of lung fibrosis and new onset of pulmonary arterial hypertension. In total, 6 patients resulted in a rating of not improved based on the CRISS in part I. The mRSSS, FVC%, CHAQ and PGA significantly improved during the 12-months follow-up in patients who were rated as improved. The predicted probability based on the CRISS algorithm resulted in an area under curve of 0.77 predicting the anchor question of improvement. In summary, 33 (70.0%) patients were correctly classified by the adult CRISS score resulting in an overall area under curve of 0.7.Conclusion:The CRISS score was evaluated in a pediatric jSSc cohort for the first time. It showed a good performance. However, it seems that the formula of part II of the CRISS score needs a calibration to pediatric jSSc patients.Disclosure of Interests:Jens Klotsche: None declared, Ivan Foeldvari Consultant of: Novartis, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Valda Stanevicha: None declared, Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, edoardo marrani: None declared, Maria T. Terreri: None declared, Flávio R. Sztajnbok: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Despina Eleftheriou: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Farzana Nuruzzaman: None declared, Nicola Helmus: None declared

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Treatment of neuroleptic-induced akathisia with the 5-HT2 antagonist mianserin

The British Journal of Psychiatry ◽

10.1192/bjp.174.3.238 ◽

1999 ◽

Vol 174 (3) ◽

pp. 238-242 ◽

Cited By ~ 49

Author(s):

Michael Poyurovsky ◽

Marina Shardorodsky ◽

Camil Fuchs ◽

Michael Schneidman ◽

Abraham Weizman

Keyword(s):

Placebo Group ◽

Low Dose ◽

Rating Scales ◽

Therapeutic Option ◽

Response To Treatment ◽

Double Blind ◽

Log Odds ◽

Double Blind Design ◽

To Receive ◽

Barnes Akathisia Scale

BackgroundSerotonin (5-HT): dopamine imbalance may underlie neuroleptic-induced akathisia.AimTo evaluate the efficacy of the 5-HT2 antagonist, mianserin in neuroleptic-induced akathisia.MethodsThirty neuroleptic-treated patients with schizophrenia were randomly allocated in a double-blind design to receive either mianserin (15 mg/day) or placebo for five days. Patients were assessed at baseline and on Days 3 and 5 by the Barnes Akathisia Scale (BARS), as well as by other relevant clinical rating scales.ResultsCompared with the placebo group, the mianserin-treated patients showed a significant reduction in all four BARS subscales by Day 5, with mean reductions in the BARS global score of 9.9% and 52.2%, respectively (P=0.006). Response to treatment (a reduction of at least two points on the BARS global subscale), was noted in six patients (40%) in the mianserin group and only one patient (9.1%) in the placebo group (P=0.04, log odds ratio 2.23).ConclusionsMianserin at a low dose may be a promising therapeutic option for patients with acute neuroleptic-induced akathisia.

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Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database

10.21203/rs.3.rs-38370/v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Yannick Allanore ◽

Sylvie Bozzi ◽

Augustin Terlinden ◽

Doerte Huscher ◽

Caroline Amand ◽

...

Keyword(s):

Systemic Sclerosis ◽

Disease Progression ◽

Health Assessment Questionnaire ◽

Multivariable Analysis ◽

Health Assessment ◽

Organ Involvement ◽

Risk Of Death ◽

Diffuse Cutaneous Systemic Sclerosis ◽

Assessment Questionnaire ◽

Questionnaire Disability

Abstract Background: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. Methods: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient’s lifetime.Results: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p < 0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p < 0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p < 0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc.Conclusions: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.

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Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.095463 ◽

2008 ◽

Vol 69 (01) ◽

pp. 193-197 ◽

Cited By ~ 137

Author(s):

V Smith ◽

J T Van Praet ◽

B Vandooren ◽

B Van der Cruyssen ◽

J-M Naeyaert ◽

...

Keyword(s):

Systemic Sclerosis ◽

Short Form ◽

Health Assessment ◽

Histopathological Study ◽

Open Label ◽

Serious Adverse Events ◽

Open Label Study ◽

Skin Sclerosis ◽

Potential Efficacy ◽

Diffuse Cutaneous Systemic Sclerosis

Objectives:The safety and potential efficacy of rituximab was examined in diffuse cutaneous systemic sclerosis (dc-SSc).Methods:A 24 week open-label study in which eight patients with dc-SSc received an infusion of 1000 mg rituximab administered at baseline and day 15, together with 100 mg methylprednisolone at each infusion. Assessment included CD19+ peripheral blood lymphocyte number, skin sclerosis score, indices of internal organ functioning, the health assessment questionnaire disability index, the 36-item Short Form health survey and histopathological evaluation of the skin.Results:Ritixumab induced effective B-cell depletion in all patients (<5 CD19+ cells/μl blood). There was a significant change in skin score at week 24 (p<0.001). Also, significant improvements were measured in the dermal hyalinised collagen content (p = 0.014) and dermal myofibroblast numbers (p = 0.011). Two serious adverse events occurred, which were thought to be unrelated to the rituximab treatment.Conclusions:Rituximab appears to be well tolerated and may have potential efficacy for skin disease in dc-SSc.This study is registered with ClinicalTrials.gov, number NCT00379431.

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OP0170 DECLINE IN FORCED VITAL CAPACITY (FVC) IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD) WITH AND WITHOUT DYSPNOEA: DATA FROM THE SENSCIS TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.834 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 101.2-102

Author(s):

E. Volkmann ◽

M. Kreuter ◽

A. M. Hoffmann-Vold ◽

M. Wijsenbeek ◽

V. Smith ◽

...

Keyword(s):

Placebo Group ◽

Lung Disease ◽

Treatment Effect ◽

Medical Officer ◽

International Committee ◽

Response To Therapy ◽

P Value ◽

Research Support ◽

Patient Reported ◽

Rate Of Decline

Background:Some patients with SSc-ILD develop dyspnoea secondary to parenchymal lung disease, while others do not report dyspnoea even when their lung function is impaired. It is unclear whether the presence of dyspnoea is associated with a worse course of SSc-ILD or with response to therapy.Objectives:To investigate the rate of decline in FVC in patients with SSc-ILD in the SENSCIS trial in subgroups by patient-reported dyspnoea at baseline.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom within ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in patients with and without dyspnoea at baseline based on the question about dyspnoea in the St. George’s Respiratory Questionnaire (SGRQ). Patients who reported having shortness of breath “most days a week”, “several days a week” or “a few days a month” (rather than “only with chest infection” or “not at all”) over the last month were considered to have dyspnoea at baseline. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test was applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 69.8% had dyspnoea at baseline. At baseline, in patients with and without dyspnoea, respectively, mean (SD) extent of fibrotic ILD on HRCT was 37.7 (21.7)% and 31.6 (19.4)%; mean (SD) FVC was 71.0 (16.3) and 76.5 (16.8) % predicted; 50.7% and 44.8% were taking mycophenolate; 53.5% and 41.9% were taking corticosteroids. In the placebo group, the rate of decline in FVC (mL/year) was similar in patients with and without dyspnoea at baseline (Figure). The effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) was numerically more pronounced in patients without dyspnoea (difference: 79.8 [95% CI: 9.8, 149.7]) than with dyspnoea (difference: 25.7 [-19.9, 71.3]), but the exploratory interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.20).Conclusion:In the SENSCIS trial, patients with SSc-ILD who had dyspnoea at baseline had a numerically greater extent of fibrotic ILD on HRCT and numerically lower FVC % predicted at baseline. The rate of decline in FVC in the placebo group was similar in patients with and without dyspnoea. Nintedanib had a numerically greater treatment effect in patients without dyspnoea. These data suggest that the presence of dyspnoea should not be used as a criterion for starting nintedanib in patients with SSc-ILD.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Michael Kreuter Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim and Roche, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme and Roche, Consultant of: Actelion, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Marlies Wijsenbeek Speakers bureau: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Consultant of: Boehringer Ingelheim (fees paid to institution), Bristol-Myers Squibb (fees paid to institution), Galapagos NV (fees paid to institution), Hoffmann-La Roche (fees paid to institution), NeRRe Therapeutics (fees paid to institution), OncoArendi Therapeutics (fees paid to institution), Respivant Sciences (fees paid to institution) and Savara (fees paid to institution), Grant/research support from: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen-Cilag NV, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Janssen-Cilag NV and Research Foundation - Flanders (FWO), Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc., Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Wim Wuyts: None declared, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Steven Sambevski Employee of: Currently an employee of Boehringer Ingelheim, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals

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THU0330 EFFECTS OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD) AND DIFFERING EXTENTS OF SKIN FIBROSIS: FURTHER ANALYSES OF THE SENSCIS TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2854 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 395-396

Author(s):

Y. Allanore ◽

V. Steen ◽

M. Kuwana ◽

C. Denton ◽

M. Matucci-Cerinic ◽

...

Keyword(s):

Placebo Group ◽

Systemic Sclerosis ◽

Topoisomerase I ◽

Statistical Testing ◽

Skin Fibrosis ◽

Annual Rate ◽

Research Support ◽

High Resolution Computed Tomography ◽

Significant Difference ◽

Rate Of Decline

Background:In the SENSCIS trial, nintedanib reduced the progression of SSc-ILD compared with placebo, as shown by a significantly lower rate of decline in forced vital capacity (FVC) over 52 weeks. There was no significant difference between treatment groups in change in modified Rodnan skin score (mRSS) at week 52. An mRSS of 18–25 has been proposed as an upper cut-off to enrich a cohort for skin-progressive patients. Progression of skin fibrosis has been associated with later progression of ILD.Objectives:To assess the effects of nintedanib on the rate of FVC decline and change in mRSS in the SENSCIS trial in subgroups by mRSS <18 and ≥18 at baseline.Methods:Patients with SSc-ILD with onset of first non-Raynaud symptom <7 years before screening and ≥10% fibrosis of the lungs on a high-resolution computed tomography scan were randomised to receive nintedanib or placebo. We analysed the rate of decline in FVC (ml/year) over 52 weeks and the change from baseline in mRSS at week 52 in subgroups by mRSS (<18; ≥18) at baseline.Results:In the nintedanib and placebo groups, respectively, 219/288 (76.0%) and 226/288 (78.5%) patients had mRSS <18 at baseline. Compared with those with mRSS <18, patients with mRSS ≥18 had a lower mean FVC % predicted (68.3% vs 73.7%) and greater proportions were taking mycophenolate at baseline (58.1% vs 45.6%), were anti-topoisomerase I antibody positive (67.4% vs 58.7%) and had diffuse cutaneous SSc (100% vs 37.8%). The mean (SE) annual rate of decline in FVC in the placebo group was numerically greater in patients who had mRSS ≥18 than mRSS <18 at baseline (-131.7 [29.2] mL/year vs -81.4 [15.4] mL/year). The effect of nintedanib vs placebo on reducing the annual rate of decline in FVC was numerically more pronounced in patients with mRSS ≥18 (difference: 88.7 mL/year [95% CI 7.7, 169.8]) than mRSS <18 (difference: 26.4 mL/year (95% CI -16.8, 69.6) at baseline, but statistical testing did not indicate heterogeneity in the treatment effect of nintedanib between subgroups (p=0.18 for treatment-by-time-by-subgroup interaction) (Figure). In the nintedanib and placebo groups, respectively, changes in mRSS at week 52 were -2.2 (0.3) and -2.1 (0.3) (difference -0.1 [95% CI -1.0, 0.7]) in patients with mRSS <18 at baseline and -2.1 (0.7) and -1.6 (0.7) (difference -0.6 [95% CI -2.1, 1.0]) in patients with mRSS ≥18 at baseline (p=0.62 for treatment-by-visit-by-subgroup interaction).Conclusion:In the placebo group of the SENSCIS trial, the rate of decline in FVC over 52 weeks was numerically greater in patients with mRSS ≥18 than <18 at baseline, while reductions in mRSS were similar. A lower rate of FVC decline was observed in patients treated with nintedanib than placebo both in patients with mRSS ≥18 and <18 at baseline.Acknowledgments:The SENSCIS trial was funded by Boehringer IngelheimDisclosure of Interests:Yannick Allanore Grant/research support from: Yannick Allanore has received grants from Inventiva, Roche and Sanofi, Consultant of: Yannick Allanore has received fees from Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Curzion, Inventiva, Roche, Sanofi, Viginia Steen Grant/research support from: The associated affiliation has received grants/research from Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Eicos, Galapagos, Immune Tolerance Network, Reata, Consultant of: Virginia Steen has acted as a consultant for Boehringer Ingelheim, Corbus, CSL Behring, Eicos, Forbius, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB, Daniel Wachtlin Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

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Randomized Trials of Autologous Hematopoietic Stem Cell Transplantation for Diffuse Cutaneous Systemic Sclerosis: Systematic Review and Meta-Analysis with Trial Sequential Analysis of Overall Mortality

Blood ◽

10.1182/blood-2018-99-115326 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 612-612 ◽

Cited By ~ 1

Author(s):

Amit Patel ◽

Yeong Jer Lim

Keyword(s):

Stem Cell ◽

Systemic Sclerosis ◽

Sequential Analysis ◽

Meta Analysis ◽

Risk Of Bias ◽

Trial Sequential Analysis ◽

Hematopoietic Stem ◽

Diffuse Cutaneous Systemic Sclerosis ◽

To Receive ◽

Overall Mortality

Abstract Background. Diffuse cutaneous systemic sclerosis (SSc) is a multi-system chronically progressive and debilitating autoimmune connective tissue disease affecting internal organs, characterized by a dysregulated immune system and the production of autoantibodies. Patients experience progressive cumulative mortality despite currently available immunosuppressive therapies. Objective. To assess the safety and efficacy of hematopoietic stem cell transplantation (SCT) with the research question: "what is the relative effect on overall mortality in patients with SSc and internal organ involvement treated with SCT compared to those treated with other available immunosuppressive therapies?" Design. Systematic review with meta-analysis of randomized controlled trials (RCTs), with trial sequential analysis (TSA) adjustment for random error and repetitive testing of sparse and accumulating data (Patel A et al BMJ 2014;349:g4561). Data sources. PubMed, PubMed Central, Web of Science, OvidSP, Cochrane central register of controlled trials (CENTRAL), clinicaltrials.gov, eudract.ema.europa.eu, controlled-trials.com, free Google search, relevant conference proceedings, hand searching of reference lists, and contact with authors as necessary. Search terms "systemic sclerosis" and "transplant". The search was last updated on 21 July 2018. Eligibility criteria. RCTs of adult patients with SSc randomized to receive SCT compared with those who were randomized to receive a non-SCT treatment were included, if overall mortality outcome data were available. Data extraction. Two reviewers independently assessed articles for inclusion, extracted data to assess risk of bias, trial methods, patients, interventions, comparisons, and outcome. The relative risk (RR) of overall mortality was calculated using a random effects model accounting for clinical heterogeneity. Primary outcome measure. Overall mortality, using intension to treat (ITT) and per protocol (PP) analyses. Risk of Bias. Assessed using the Cochrane Risk of Bias Assessment Tool. Results. There were three eligible RCTs (ASSIST 2011, ASTIS 2014, SCOT 2018), including 250 patients followed for up to 7.8 years (156 patients in Europe and 94 in North America). All trials were open label and assessed as at unclear risk of bias. Peripheral blood stem cell collection: 2-4 g/m2 cyclophosphamide before reinfusion of thawed cryopreserved 2 million CD34+ cells/kg, or GCSF and CD34+ cell enrichment before reinfusion of thawed cells (median of 5.6 million cells/kg). Conditioning was cyclophosphamide 200 mg/kg with 6.5-7.5 mg/kg rabbit anti-thymocyte globulin (ATG) or 120 mg/kg with 8 Gy total body irradiation (TBI) (lung and kidney shielding with 2 Gy limit) and 90 mg/kg equine ATG. Supportive care included corticosteroids, angiotensin converting enzyme inhibitors (usually lisinopril), and aciclovir. Control group treatments comprised monthly cyclophosphamide, 0.5-1 g/m2, 6-12 infusions. Significant overall mortality benefit was observed in the SCT group, with both an ITT (RR 0.60, 95% confidence interval (CI) 0.40-0.90; P=0.01) and PP analysis (RR 0.52, 95% CI 0.33-0.83; P=0.006). Statistical heterogeneity was absent (I2=0%). SCT benefit was robust to TSA adjustment for both the ITT (RR 0.60, 95% CI 0.36-0.98; P=0.014; diversity adjusted information size (D2=0%) and PP analyses (RR 0.51, 95% CI 0.31-0.86; P=0.004; D2=0%). The information size for an ITT model had >70% power (Fig 1), while the PP model had >90% power (Fig 2). The corresponding number needed to treat (NNT) to prevent 1 death was 7 (95% CI 4-29) for the ITT analysis and 5 (95% CI 3-11) for the PP analysis. However, significantly higher CTCAE grade 3-4 infective (P<0.01) and hematological (P<0.01) adverse events were reported in the SCT group compared to control, with no difference for cardiovascular (P=0.92) and respiratory (P=0.24) events. More viral infection or reactivation events were reported in the SCT group compared to control (P=0.05): CMV (P=0.01), EBV (P=0.08), HSV (P=0.59). Importantly, subsequent malignancy was similar for both groups (P=0.96), 4-5%. Conclusions. Our analysis has sufficient information size to indicate that autologous SCT for patients with SSc and internal organ involvement is safe and efficacious. The magnitude of the reduction in long-term mortality of autologous SCT over other available therapies may be practice changing. Disclosures No relevant conflicts of interest to declare.

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THU0363 EFFECTS OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD) AND NORMAL VERSUS ELEVATED C-REACTIVE PROTEIN (CRP) AT BASELINE: ANALYSES FROM THE SENSCIS TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3711 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 413-414

Author(s):

G. Riemekasten ◽

P. Carreira ◽

L. A. Saketkoo ◽

M. Aringer ◽

L. Chung ◽

...

Keyword(s):

Placebo Group ◽

High Sensitivity ◽

Similar Proportion ◽

P Value ◽

Research Support ◽

Absolute Increase ◽

Reactive Protein ◽

Inflammatory Phenotype ◽

Rate Of Decline ◽

To Receive

Background:In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks. Elevated CRP is a marker of an inflammatory phenotype and has been associated with a greater rate of decline in FVC and higher mortality in patients with SSc.Objectives:To assess the effects of nintedanib in subgroups by CRP at baseline in the SENSCIS trial.Methods:Patients with SSc-ILD with onset of first non-Raynaud symptom <7 years and ≥10% fibrosis of the lungs on HRCT were randomised to receive nintedanib or placebo. We analysed the rate of decline in FVC (mL/year) over 52 weeks, the proportion of patients with an absolute increase in FVC ≥3% predicted (proposed as the minimal clinically important difference for improvement in FVC in patients with SSc-ILD), and absolute change from baseline in mRSS at week 52 in subgroups with normal vs elevated high-sensitivity CRP (≤4.99 vs >4.99 mg/L) at baseline.Results:Of patients with available data, 78/270 (28.9%) and 74/261 (28.4%) in the nintedanib and placebo groups, respectively, had CRP >4.99 mg/L at baseline. Compared with patients with lower CRP, those with CRP >4.99 mg/L included a similar proportion of patients who were ATA-positive (61.8% vs 60.2%, respectively), a greater proportion with diffuse cutaneous SSc (63.2% vs 49.3%) and had a higher mean mRSS (13.7 vs 10.2) and lower mean FVC % predicted (68.6% vs 73.9%). The adjusted annual rate of decline in FVC in the placebo group was numerically greater in patients with CRP >4.99 than ≤4.99 mg/L at baseline (-106.6 [SE 27.6] vs -83.0 [17.1] mL/year). The effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in patients with CRP >4.99 than ≤4.99 mg/L at baseline but the treatment-by-time-by-subgroup interaction p-value did not indicate heterogeneity in the effect of nintedanib between subgroups (p=0.70) (Figure). In the nintedanib and placebo groups, respectively, the proportions of patients with an absolute increase in FVC ≥3% predicted at week 52 were 20.4% and 15.0% in those with CRP ≤4.99 mg/L and 24.4% and 14.9% in those with CRP >4.99 mg/L at baseline (treatment-by-subgroup interaction p=0.59); adjusted mean changes in mRSS at week 52 were -2.2 (SE 0.3) and -2.1 (0.3) in those with CRP ≤4.99 mg/L (difference -0.1 [95% CI -1.0, 0.8]) and -2.3 (0.5) and -1.0 (0.5) in those with CRP >4.99 mg/L at baseline (difference -1.2 [-2.7, 0.2]; treatment-by-visit-by-subgroup interaction p=0.20).Conclusion:In the SENSCIS trial, the rate of decline in FVC over 52 weeks in the placebo group was numerically greater in patients with elevated CRP at baseline. Nintedanib reduced the rate of decline in FVC both in patients with normal and elevated CRP at baseline, with a numerically greater effect in patients with elevated CRP.Disclosure of Interests:Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Lesley Ann Saketkoo Grant/research support from: Corbus Pharmaceuticals, United Therapeutics, Consultant of: Boehringer Ingelheim, Eicos Sciences, Speakers bureau: Boehringer Ingelheim, Martin Aringer Consultant of: Boehringer Ingelheim, Roche, Speakers bureau: Boehringer Ingelheim, Roche, Lorinda Chung Grant/research support from: United Therapeutics, Boehringer Ingelheim, Consultant of: Bristol-Myers Squibb, Boehringer Ingelheim, Mitsubishi Tanabe, Eicos Sciences, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Corinna Miede Employee of: Employee of Boehringer Ingelheim, Susanne Stowasser Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB

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Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database

Arthritis Research & Therapy ◽

10.1186/s13075-020-02329-2 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Yannick Allanore ◽

◽

Sylvie Bozzi ◽

Augustin Terlinden ◽

Doerte Huscher ◽

...

Keyword(s):

Systemic Sclerosis ◽

Disease Progression ◽

Health Assessment Questionnaire ◽

Multivariable Analysis ◽

Health Assessment ◽

Organ Involvement ◽

Risk Of Death ◽

Diffuse Cutaneous Systemic Sclerosis ◽

Assessment Questionnaire ◽

Questionnaire Disability

Abstract Background Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. Methods This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient’s lifetime. Results The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p < 0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p < 0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p < 0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. Conclusions HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.

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