Function In Systemic Sclerosis Research Articles

Factors associated with physical function among people with systemic sclerosis: a SPIN cohort cross-sectional study.

To compare physical function in systemic sclerosis (SSc, scleroderma) to general population normative data and identify associated factors. Scleroderma Patient-centered Intervention Network Cohort participants completed the Physical Function domain of the Patient-Reported Outcomes Measurement Information System Version 2 upon enrolment. Multivariable linear regression was used to assess associations of sociodemographic, lifestyle, and disease-related variables. Among 2,385 participants, mean physical function T-score (43.7, SD = 8.9) was ∼2/3 of a standard deviation (SD) below the US general population (mean = 50, SD = 10). Factors associated in multivariable analysis included older age (-0.74 points per SD years, 95% CI -0.78 to -1.08), female sex (-1.35, -2.37 to -0.34), fewer years of education (-0.41 points per SD in years, -0.75 to -0.07), being single, divorced, or widowed (-0.76, -1.48 to -0.03), smoking (-3.14, -4.42 to -1.85), alcohol consumption (0.79 points per SD drinks per week, 0.45-1.14), BMI (-1.41 points per SD, -1.75 to -1.07), diffuse subtype (-1.43, -2.23 to -0.62), gastrointestinal involvement (-2.58, -3.53 to -1.62), digital ulcers (-1.96, -2.94 to -0.98), moderate (-1.94, -2.94 to -0.93) and severe (-1.76, -3.24 to -0.28) small joint contractures, moderate (-2.10, -3.44 to -0.76) and severe (-2.54, -4.64 to -0.44) large joint contractures, interstitial lung disease (-1.52, -2.27 to -0.77), pulmonary arterial hypertension (-3.72, -4.91 to -2.52), rheumatoid arthritis (-2.10, -3.64 to -0.56) and idiopathic inflammatory myositis (-2.10, -3.63 to -0.56). Physical function is impaired for many individuals with SSc and associated with multiple disease factors.

Assessment of foot impairment in systemic sclerosis: a cross-sectional study.

To assess foot function in Systemic Sclerosis (SSc) and its association with sociodemographic and clinical factors. To evaluate mobility, foot alterations, foot pain, and foot care in these patients. Consecutive SSc patients underwent structured interviews and physical examinations. Disability was assessed using Health Assessment Questionnaire (HAQ) and Scleroderma Health Assessment Questionnaire. (SHAQ). Foot function was measured using Foot Function Index (FFI), foot pain using a numeric pain scale (NPS), and mobility using Timed-UP-Go test (TUG). 101 patients were included. Forefoot pain was observed in 50.5%, hindfoot pain in 31.7%, foot ulcers in 6.9%, foot plantar callosities in 38.6%, foot arthritis in 2.97%, hallux valgus in 9.9%, claw toes in 5%, and valgus ankle in 3% of patients. The mean FFI was 3.54 (±2.6), NPS was 6.08 (±3.58), and TUG test was 10.52 (±6.5) seconds. Higher FFI scores, increased NPS, and prolonged TUG were associated with Raynaud's phenomenon severity, SHAQ, and HAQ. 36.6% of patients reported never having their feet examined, and only 32.7% had their feet examined within the past year. Foot dysfunction and pain are common in SSc. Higher FFI scores, increased pain, and prolonged TUG duration were linked to disability (HAQ and SHAQ). These analyses should be considered exploratory and require confirmation in external cohorts. Routine foot examinations were lacking in clinical practice. Improved attention for evaluating and caring for the feet in SSc patients is needed.

Preparation of Oxidized and Reduced PTP4A1 for Structural and Functional Studies.

The formation of a reversible disulfide bond between the catalytic cysteine and a spatially neighboring cysteine (backdoor) in protein tyrosine phosphatases (PTPs) serves as a critical regulatory mechanism for maintaining the activity of protein tyrosine phosphatases. The failure of such protection results in the formation of irreversibly oxidized cysteines into sulfonic acid in a highly oxidative cellular environment in the presence of free radicals. Hence, it is important to develop methods to interconvert PTPs into reduced and oxidized forms to understand their catalytic function in vitro. Protein tyrosine phosphatase 4A type 1 (PTP4A1), a dual-specificity phosphatase, is catalytically active in the reduced form. Unexpectedly, also its oxidized form performs a key biological function in systemic sclerosis (SSc) by forming a kinase-phosphatase complex with Src kinases. Thus, we developed simple and efficient protocols for producing oxidized and reduced PTP4A1 to elucidate their biological function, which can be extended to study other protein tyrosine phosphatases and other recombinantly produced proteins.

Prognostic significance of pulmonary hypertension in patients with connective tissue disorders: review and meta-analysis

Abstract Background Pulmonary hypertension (PH) is a frequent complication of connective tissue disorders (CTD) with major impact on prognosis of the disease, especially in patients with systemic sclerosis (SSc). Recently suggested new classification based on the hemodynamic assessment of PH and currently available pharmacologic treatment can be associated with improved survival, therefore underlining the group of the patients with PH and most affected survival function is crucial. Objectives of our study were to perform systemic review and meta-analysis of published literature evaluating survival function in patients with SSc and Systemic lupus erythematosus (SLE) with and without PH, also to compare PH-associated survival function in between patients with SSc, systemic lupus erythematosus (SLE), other connective tissue disorders (CTD) and conditions characterized with PH. Methods Literature search strategies, inclusion and exclusion criteria, outcome measurements, and statistical methods were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE). Case control studies evaluating PH-associated survival function in SSc (including interstitial lung disease -ILD) and SLE patients and also studies comparing survival function among SSc, various CTD entities and conditions associated with PH were included in the analysis. Results A total of 2114 papers were collected according to our searching criteria, of those 7 studies including 1470 SSc patients with PH and 1368 SSc patients without PH, also 4 studies including 108 SLE patients with PH and 1288 SLE patients without PH and evaluated survival function were selected. We also performed meta-analysis of 6 studies (including 777 SSc, 249 SLE, 41 idiopathic PH (IPH), 49 primary PH (PPH) and 29 primary Sjogren’s syndrome (pSS) patients) comparing PH-associated survival function in different subgroups. The mean pooled follow-up was 5.4 years (5.4±4.4 year). We observed that SSc patients with PH showed worst survival as compared to SSc patients without PH [RR (95 %CI) 2.20 (1.52 to 3.20); p<0.00001] (Figure1). Same pattern was observed in patients with SLE [RR (95 %CI) 5.20 (2.34 to 11.56); p<0.00001] (Figure 1). Overall, SSc patients with PH were characterized with lower survival function as compared to other reasons of PH including SLE [RR (95 %CI) 1.77 (1.43 to 2.19); p<0.00001] (Figure 2). Conclusions Patients with SSc associated PH are characterized with significantly lower survival function as compared to SSc patients without PH. Among various CTD and other entities of PH, SSc shows worst survival, underlining prognostic significance of detection and evaluation of PH according to currently established approach.Figure 1Figure 2

OC 56.4 GPVI-Activated Platelets Drive the Neutrophil Profibrotic Function in Systemic Sclerosis

OC 56.4 GPVI-Activated Platelets Drive the Neutrophil Profibrotic Function in Systemic Sclerosis

Autologous Stem Cell Transplantation With Intensity Modulated Total Body Irradiation Conditioning for Systemic Sclerosis

Autologous stem cell transplantation (HSCT) using myeloablative total body irradiation (TBI) and anti-thymocyte globulin (ATG) as a conditioning regimen has become a standard treatment option for certain patients with systemic sclerosis (SSc). Normal organs are more radiosensitive and prone to compromised function in SSc, and therefore lungs and kidneys require dose reduction. We evaluated the role of intensity modulated radiation therapy (IMRT) TBI compared to standard anteroposterior (AP)/posteroanterior (PA) TBI technique. Patients with SSc who underwent HSCT with TBI between 2017 and 2022 were eligible. All patients underwent conditioning with equine ATG, cyclophosphamide 120 mg/kg, and IMRT TBI to a total dose of 800 cGy in 200 cGy fractions. Patients were replanned using an AP/PA technique for dosimetric comparison. Patients were evaluated for outcomes including event-free survival (EFS), overall survival (OS), disease-modifying antirheumatic drug-free survival (DMARD-FS), and treatment related mortality (TRM). 14 patients were eligible for our analysis. Median follow-up was 34.6 months (1.0-51.7 months). There was one case of TRM secondary to respiratory failure. The 24-month OS, EFS, and DMARD-FS estimates were 92.9%, 74.3%, and 70.0%, respectively. Three patients experienced adverse events, which included respiratory failure (n=1), renal failure (n=1), and death (n=1). Five patients subsequently initiated DMARDs, but three did so due to worsening skin symptoms without other major organ dysfunction. On dosimetric analysis, the mean dose to the planning target volume (PTV) was significantly higher on the IMRT compared to the AP/PA plans (809.4 cGy versus 728.5 cGy, p<0.001). The mean dose to the lungs (239.5 cGy versus 443.9 cGy, p<0.001) and kidneys (204.9cGy versus 281.2 cGy, p<0.001) was significantly lower. Use of IMRT TBI as part of the conditioning regimen for HSCT for SSc yields improved dosimetry with efficacy and toxicity outcomes comparable with published data.

Right Ventricular Morphology and Function after Exercise Training in People with Systemic Sclerosis: A Randomized Controlled Pilot Study

Vascular dysfunction and its concomitant multi-organ involvement, including cardiac involvement, affects prognosis in systemic sclerosis (SSc) patients. Regular exercise has demonstrated to be able to improve vascular function in SSc. However, the effects of an exercise program on the heart and specifically in right ventricular (RV) morphology and function in SSc have yet to be explored. The study aimed to examine whether a 3-month combined exercise program can affect RV morphology and function in SSc patients. Twenty-eight SSc patients were randomly allocated to either the exercise training (ET) or the control (CON) group. Baseline and follow-up assessments consisted of a cardiopulmonary exercise test along with both a conventional and a two-dimensional speckle tracking echocardiography (2DSTE) focused on RV morphology and function. Following the baseline assessments, Group ET participated in a supervised combined exercise program for 12 weeks, while group CON received their usual care. The ET group demonstrated increases in peak oxygen consumption by 25.1% (p < 0.001), global RV free wall longitudinal systolic strain by 6.69% (p < 0.03), RV free wall longitudinal systolic strain of the basal segment by 13.5% (p < 0.001), and global RV four-chamber longitudinal systolic strain by 6.76% (p < 0.03) following the exercise program. No differences were observed in group CON. Combined exercise improved cardiorespiratory efficiency and indices of RV systolic function, as assessed by the 2DSTE, in SSc patients.

Automatic Pulmonary Function Estimation From Chest CT Scans Using Deep Regression Neural Networks: The Relation Between Structure and Function in Systemic Sclerosis

Automatic Pulmonary Function Estimation From Chest CT Scans Using Deep Regression Neural Networks: The Relation Between Structure and Function in Systemic Sclerosis

Deficiency of inhibitory TLR4 homolog RP105 exacerbates fibrosis.

Activation of TLR4 by its cognate damage-associated molecular patterns (DAMPs) elicits potent profibrotic effects and myofibroblast activation in systemic sclerosis (SSc), while genetic targeting of TLR4 or its DAMPs in mice accelerates fibrosis resolution. To prevent aberrant DAMP/TLR4 activity, a variety of negative regulators evolved to dampen the magnitude and duration of the signaling. These include radioprotective 105 kDa (RP105), a transmembrane TLR4 homolog that competitively inhibits DAMP recognition of TLR4, blocking TLR4 signaling in immune cells. The role of RP105 in TLR4-dependent fibrotic responses in SSc is unknown. Using unbiased transcriptome analysis of skin biopsies, we found that levels of both TLR4 and its adaptor protein MD2 were elevated in SSc skin and significantly correlated with each other. Expression of RP105 was negatively associated with myofibroblast differentiation in SSc. Importantly, RP105-TLR4 association was reduced, whereas TLR4-TLR4 showed strong association in fibroblasts from patients with SSc, as evidenced by PLA assays. Moreover, RP105 adaptor MD1 expression was significantly reduced in SSc skin biopsies and explanted SSc skin fibroblasts. Exogenous RP105-MD1 abrogated, while loss of RP105 exaggerated, fibrotic cellular responses. Importantly, ablation of RP105 in mice was associated with augmented TLR4 signaling and aggravated skin fibrosis in complementary disease models. Thus, we believe RP105-MD1 to be a novel cell-intrinsic negative regulator of TLR4-MD2-driven sustained fibroblast activation, representing a critical regulatory network governing the fibrotic process. Impaired RP105 function in SSc might contribute to persistence of progression of the disease.

Adipose‐Derived Regenerative Cell Transplantation for the Treatment of Hand Dysfunction in Systemic Sclerosis: A Randomized Clinical Trial

ObjectiveHand dysfunction is common in systemic sclerosis (SSc). We undertook this study to evaluate the capacity of autologous adipose‐derived regenerative cells (ADRCs) to improve hand function in SSc patients.MethodsThe Scleroderma Treatment with Celution Processed Adipose Derived Regenerative Cells Trial was a prospective, randomized, double‐blind trial of ADRCs, in which ADRCs were obtained from patients with SSc by small‐volume adipose tissue harvest, and the fingers of each patient were injected with ADRCs. The primary end point was change in hand function at 24 and 48 weeks, assessed using the Cochin Hand Function Scale (CHFS). One of the secondary end points included the change in Health Assessment Questionnaire disability index (HAQ DI) at 48 weeks. Separate prespecified analyses were performed for patients with diffuse cutaneous SSc (dcSSc) and those with limited cutaneous SSc (lcSSc).ResultsEighty‐eight patients were randomized to receive ADRCs (n = 48 [32 patients with dcSSc and 16 with lcSSc]) or placebo (n = 40 [19 patients with dcSSc and 21 with lcSSc]). Change in hand function according to CHFS score was numerically higher for the ADRC group compared to the placebo group but did not achieve statistical significance (mean ± SD improvement in the CHFS score at 48 weeks 11.0 ± 12.5 versus 8.9 ± 10.5; P = 0.299). For patients with dcSSc, the between‐group difference in the CHFS at 48 weeks was 6.3 points (nominal P = 0.069). For the secondary end point, the dcSSc group exhibited a between‐group difference of 0.17 points in the HAQ DI (nominal P = 0.044) at 48 weeks. Of the ADRC‐treated patients with dcSSc, 52% reported improvement greater than the minimum clinically important difference for both CHFS and HAQ DI compared to 16% in the placebo group (nominal P = 0.016). Small‐volume adipose tissue harvest and ADRC treatment were well tolerated.ConclusionWhile the primary end point of this trial was not achieved, efficacy trends were observed in patients with dcSSc. Adipose tissue harvest and ADRC injection were demonstrated to be feasible. Further clinical trials of this intervention in the setting of dcSSc are warranted.

Defining minimal detectable difference in echocardiographic measures of right ventricular function in systemic sclerosis

BackgroundEchocardiography (2DE) is integral for screening and longitudinal evaluation of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). In the present study, we sought to establish the reliability, repeatability, and reproducibility of 2DE parameters in SSc patients with and without PAH and to define the minimal detectable difference (MDD), the smallest change detected beyond measurement error.MethodsSSc patients without known PAH and with invasively confirmed PAH on stable therapies underwent 2DE with strain at two time points. Analysis of variance (ANOVA) and coefficients of variation (CV) were calculated to assess for repeatability, reliability, and reproducibility. Intra- and inter-observer agreement were assessed using intraclass correlation. Bland-Altman analysis explored the level of agreement between evaluations. MDD was calculated using the standard error of measurement for each parameter by cohort.ResultsANOVA demonstrated few significant differences between evaluations across groups. Global right ventricular longitudinal systolic strain (GRVLSS, 9.7%) and fractional area change (FAC, 21.3%) had the largest CV, while tricuspid annular plane excursion (TAPSE), S’ wave, and right ventricular outflow track velocity time integral (RVOT VTI) were 0.87%, 3.2%, and 6.0%, respectively. Intra- and inter-observer agreement was excellent. MDD for TAPSE, FAC, S’ wave, RVOT VTI, GRVLSS, and RVSP were 0.11 cm, 0.03%, 1.27 cm/s, 0.81 cm, 1.14%, and 6.5 mmHg, respectively.ConclusionsWe demonstrate minimal measurement error in clinically important 2DE-based measures in SSc patients with and without PAH. Defining the MDD in this population has important implications for PAH screening, assessment of therapeutic response, and sample size calculations for future clinical trials.

Tetrahydrobiopterin Administration Augments Exercise-Induced Hyperemia and Endothelial Function in Patients With Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare, auto-immune disease with variably progressive fibrosis of the skin and internal organs, as well as vascular dysfunction. Recently, we demonstrated a decrement in exercising skeletal muscle blood flow and endothelium-dependent vasodilation in SSc, but the mechanisms responsible for these impairments have not been investigated. Thus, we sought to determine if acute administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS), would improve hyperemia and brachial artery vasodilation during progressive handgrip exercise in SSc. Thirteen patients with SSc (63 ± 11 years) participated in this placebo-controlled, randomized, double-blind, crossover study. Tetrahydrobiopterin (10 mg/kg) administration resulted in a ~4-fold increase in circulating BH4 concentrations (P < 0.05). Cardiovascular variables at rest were unaffected by BH4 (P > 0.05). During handgrip exercise, BH4 administration increased brachial artery blood flow (placebo: 200 ± 87; BH4: 261 ± 115 ml/min; P < 0.05) and vascular conductance (placebo: 2.0 ± 0.8; BH4: 2.5 ± 1.0 ml/min/mmHg; P < 0.05), indicating augmented resistance artery vasodilation. Tetrahydrobiopterin administration also increased brachial artery vasodilation in response to exercise (placebo: 12 ± 6; BH4: 17 ± 7%; P < 0.05), resulting in a significant upward shift in the slope relationship between Δ brachial artery vasodilation and Δ shear rate (placebo: 0.030 ± 0.007; BH4: 0.047 ± 0.007; P < 0.05) that indicates augmented sensitivity of the brachial artery to vasodilate to the sustained elevations in shear rate during handgrip exercise. These results demonstrate the efficacy of acute BH4 administration to improve both resistance and conduit vessel endothelial function in SSc, suggesting that eNOS recoupling may be an effective strategy for improving vasodilatory capacity in this patient group.

Heterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of "scleroderma esophagus".

Although esophageal dysmotility is common in systemic sclerosis (SSc)/scleroderma, little is known regarding the pathophysiology of motor abnormalities driving reflux severity and dysphagia. This study aimed to assess primary and secondary peristalsis in SSc using a comprehensive esophageal motility assessment applying high-resolution manometry (HRM) and functional luminal imaging probe (FLIP) Panometry. A total of 32 patients with scleroderma (28 female; ages 38-77; 20limited SSc, 12 diffuse SSc) completed FLIP Panometry and HRM. Secondary peristalsis, i.e., contractile responses (CR), was classified on FLIP Panometry by pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), or absent (ACR). Primary peristalsis on HRM was assessed according to the Chicago classification. The manometric diagnoses were 56% (n=18) absent contractility, 22% (n=7) ineffective esophageal motility (IEM), and 22% (n=7) normal motility. Secondary peristalsis (CRs) included 38% (n=12) ACR, 38% (n=12) IDCR, 19% (n=6) BCR, and 15% (n=5) NCR. The median (IQR) esophagogastric junction (EGJ) distensibility index (DI) was 5.8mm2 /mmHg (4.8-10.1) mm2 /mmHg; EGJ-DI was >8.0mm2 /mmHg in 31%, and >2.0mm2 /mmHg in 100% of patients. Among 18 patients with absent contractility on HRM, 11had ACR, 5had IDCR, and 2had BCR. Among 7 patients with IEM, 1had ACR, 5had IDCR, and 1NCR. All of the patients with normal peristalsis had NCR or BCR. This was the first study assessing combined HRM and FLIP Panometry in a cohort of SSc patients, which demonstrated heterogeneity in primary and secondary peristalsis. This complementary approach facilitates characterizing esophageal function in SSc, although future study to examine clinical outcomes remains necessary.

Laser speckle contrast analysis is a reliable measure of digital blood perfusion in Black Africans with systemic sclerosis.

Laser speckle contrast analysis (LASCA) is evolving as a promising non-invasive tool to assess cutaneous microvascular function in systemic sclerosis (SSc). Reliability studies have mainly focused on Caucasian populations. To determine for the first time the inter-rater reliability of fingertip blood perfusion (BP) using LASCA in Black South African patients with SSc. Consecutive Black adult patients with SSc were evaluated for peripheral BP using LASCA. Mean BP in defined regions of interest for dorsal fingertips and volar fingertips were measured in two subgroups of 20 SSc patients, each by three independent operators. Two operators were experienced in the use of the LASCA instrument and one was newly trained. Standardised protocols for conditions were followed for all measurements. Inter-rater reliability was tested using the intraclass correlation coefficient (ICC). The majority (87.5%) of the 40 patients included were females and 67.5% had diffuse cutaneous SSc. The mean age (standard deviation) was 48.5 (9.9) years and the median disease duration (interquartile range) was 8.5 (4, 13) years. There was good to excellent agreement, inter-rater ICC (dorsal fingertip range: 0.86-0.97 and volar fingertip range: 0.85-0.96), in both subgroups irrespective of operator skill. LASCA is a credible instrument in patients of Black ethnicity with SSc, and across operator experience.

Downregulated IRF8 in Monocytes and Macrophages of Patients with Systemic Sclerosis May Aggravate the Fibrotic Phenotype

Monocytes and macrophages may be involved in the pathogenesis of systemic sclerosis (SSc); however, the etiology and regulation of monocyte and macrophage function in SSc remain unknown. IRF8 is a transcriptional regulator that is essential for the differentiation and function of monocytes and macrophages and thus may be involved in the regulation of macrophage phenotypes in SSc fibrosis. In this study, we measured IRF8 levels in circulating monocytes of 26 patients with SSc (diffuse cutaneous SSc, n= 11; limited cutaneous SSc, n= 15) and 14 healthy controls. IRF8 levels were significantly suppressed in monocytes of patients with diffuse cutaneous SSc and correlated negatively with the modified Rodnan total skin thickness score. Next, we assessed expression levels of cell surface markers, cytokine profiles, and components of extracellular matrix in IRF8-silenced monocyte-derived macrophages. IRF8-silenced monocyte-derived macrophages displayed an M2 phenotype and significantly upregulated mRNA and protein levels of profibrotic factors and extracellular matrix components. Finally, we assessed skin fibrosis in myeloid cell-specific IRF8 conditional knockout (Irf8flox/flox; Lyz2Cre/+) mice and found upregulated mRNA levels of extracellular matrix components and increased bleomycin-induced skin fibrosis. In conclusion, altered IRF8 regulation in monocytes and macrophages may be involved in SSc pathogenesis.

Effect of short-interval rituximab and high-dose corticosteroids on kidney function in systemic sclerosis: Long-term experience of a single centre.

IntroductionScleroderma renal crisis (SRC) is a rare but one of the most recognised complications of systemic sclerosis (SSc). Corticosteroid (CS) use has been considered as a major risk factor for SRC. Several studies reported the efficacy of rituximab (RTX) with an acceptable safety profile in SSc. However, data on the long‐term effect of high‐dose CS concomitant to RTX on kidney function are lacking.MethodsWe retrospectively analysed SSc patients (n = 35) treated with a lower dosage and short‐interval RTX and concomitant high‐dose CS at the Department of Internal Medicine at the Medical University of Graz between 2010 and 2019. The kidney function was assessed using the estimated glomerular filtration rate (eGFR) at every RTX admission. The annual decline of kidney function was evaluated by linear mixed model analysis.ResultsAt the RTX initiation, one patient had a decreased kidney function indicated by eGFR < 60 mL/min/1.73 m2 (median: 96 mL/min/1.73 m2; interquartile range (IQR): 43‐136). Patients received RTX and complementary high‐dose CS for a median follow‐up time of 3.4 years (range 0.6‐9.5). A linear mixed model analysis with the patient as random effect and time from first RTX as fixed effect estimated an annual decline of 1.98 mL/min/1.73 m2 of the eGFR (95% confidence interval: [−2.24, −1.72]; P <.001). During the follow‐up period, no patient experienced SRC or a significant drop in kidney function.ConclusionsA regular, high‐dose CS given contemporary to RTX seems to be a safe option for kidney function in patients with SSc. Our findings provide additional knowledge in risk evaluation and planning of individualised therapies or designing clinical studies using RTX.

P160 Systemic sclerosis physiotherapy in the digital age

Abstract Background Clinical outcome measures for hand function in systemic sclerosis (SSc) can be assessed using validated questionnaires such as the Cochin hand function questionnaire (CHFS). The CHFS can evaluate the physical efficacy of hand physiotherapy. However, there is currently no validated questionnaire for assessing patient motivation to engage in hand exercises, which is a crucial consideration for any exercise regime. The aim of this study was to evaluate patient opinions of their own hand function status and motivation to complete hand exercises. This research sits within a larger study investigating hand function pre and post-conventional therapy and a new innovative virtual rehabilitation programme. Methods Twenty patients diagnosed with limited and diffuse cutaneous SSc (lcSSc and dcSSc), meeting the 2013 ACR criteria for SSc, were recruited from a tertiary referral rheumatology clinic (mean age: 55yrs; range 34-74yrs; female: n = 18; white British: 95%; dcSSc: n = 10; lcSSc: n = 10; mean mRSS: 10; mean age at diagnosis: 43yrs). All participants completed a novel questionnaire developed for this study to evaluate their experience with and motivation for completing hand exercises. Additionally, baseline characteristics were surveyed as well as a timeline of disease characteristics. Subsequent data analysis included Fisher’s exact testing and Spearman’s bivariate correlation. Results Half of all patients surveyed reported that hand function limited their ability to perform tasks of daily living, but they still retained independence. 65% (n = 13) of participants performed hand function exercises for a mean 25 weeks, with 30.8% being only a “little motivated”. A total of 65% were referred for physiotherapy. There was a strong positive correlation (Spearman’s rho 0.786) between older age at disease diagnosis and motivation to do hand exercises. However, there was no correlation (Spearman’s rho 0.027) between how motivated an individual was to do hand exercises and the number of weeks exercises were performed. The dcSSc group of patients were found to have performed hand exercises more than lcSSc (Fisher’s Exact Test, p = 0.03). Conclusion Across all patients, the lack of association between motivation and weeks of hand exercises completed indicates that there are barriers faced by patients with SSc who want to do physiotherapy. The strong correlation between the age at which the disease was diagnosed and a patient’s motivation to do physiotherapy is not supported by the available literature, as studies show that adherence to physiotherapy is associated more closely to education, socioeconomic background and social support. An additional independent study specific to age, with the consideration of confounders is necessary to explore this. An easy to use digital rehabilitation intervention could help actualise motivation and make physiotherapy more accessible. This needs to be validated in a larger cohort. Disclosures S. Addous None. J. Wood None. E. Eusterwiemann None. M.E. Anderson None.

P153 Tocilizumab in systemic sclerosis: real world experience from a single centre cohort supports potential benefit on lung function for anti-topoisomerase (Scl-70) positive subgroup

Abstract Background The FaSScinate and FocuSSced trials of tocilizumab versus placebo in early diffuse systemic sclerosis (SSc) highlighted the potential impact of tocilizumab on lung function with preservation of lung function in those treated with tocilizumab versus placebo, despite only a trend of benefit for skin fibrosis. Our centre have been using tocilizumab to treat SSc patients and overlap inflammatory arthritis, in line with NICE guidance treatment for inflammatory arthritis. We report here our experience of tocilizumab in SSc and the impact on lung function. Methods A retrospective medical chart review of patients attending our centre with SSc and having ever been on tocilizumab were identified, mostly with overlap inflammatory arthritis. Patients included in the FaSScinate trial were excluded, however patients receiving compassionate use of tocilizumab following the phase 3 FocuSSced trial were included. Mann-Whitney-U test was used for statistical analysis. Results In total 32 patients were identified. 68.8% (n = 22) of patients had a diagnosis of dcSSc. 75% (n = 24) patients were female. The most common autoantibodies were ATA (anti-topoisomerase antibody) (34.3%) and ARA (anti-RNA polymerase-III antibody) (18.8%). 46.9% (n = 17) patients had known interstitial lung disease. 6 patients received tocilizumab on a compassionate basis following completion of the open label phase of the focuSSced clinical trial, the remainder had overlap inflammatory arthritis. Mean age of disease onset was 38.6 years, and the median disease duration to tocilizumab initiation was 7.9 years. 11 patients discontinued tocilizumab: 6 due to cessation of the compassionate use access, 2 due to side effects, 3 due to lack of benefit. 75% (n = 24) patients had serial lung function data to compare FVC and DLCO before and after initiation of treatment. Baseline FVC prior to tocilizumab was 3.09L (sd = 0.98). To standardise results, the yearly change rate in FVC and DLCO was calculated. Median change in % predicted FVC was -1.5% (IQR=0.107) and median change in % predicted DLCO was -0.5% (IQR=0.061). Subgroup analysis revealed a significant difference between autoantibody groups and change in FVC while on tocilizumab. It was notable that there was an increase in median change in FVC in patients with ATA antibody (3.27%, IQR=0.1355) whereas there was a decrease in median change in FVC in all other autoantibody groups (-4.7%, IQR=0.111, p = 0.0019). There was a near significant difference in change in DLCO between these antibodies at 12 months (p = 0.056) in favour of improvement in ATA subgroup. Conclusion We report our experience of the impact of tocilizumab on lung function in SSc. Consistent with trial results, there is a signal of potential benefit for lung function among those with ATA autoantibody irrespective of disease subset. As this autoantibody confers high risk of extensive lung fibrosis in SSc it may help in future case selection. Disclosures K.E.N. Clark None. Y. Suleman None. S.I. Nihtyanova None. V.H. Ong None. C.P. Denton Grants/research support; Actelion, GlaxoSmithKline, Bayer, Sanofi, lnventiva, Boehringer Ingelheim, Roche, Bristol Myers Squibb, CSL Behring, UCB, Leadiant Biosciences.

Natural history of systemic sclerosis–related interstitial lung disease: How to identify a progressive fibrosing phenotype

The natural history of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is highly variable. Historical observational studies have demonstrated that the greatest decline in lung function in SSc occurs early in the course of the disease; however, not all patients experience a decline in lung function even in the absence of treatment. Furthermore, among patients who do experience a decline in lung function, the rate of decline can be either rapid or slow. The most common clinical phenotypes of SSc-ILD therefore: (i) Rapid Progressors, (ii) Gradual Progressors, (iii) Stabilizers and (iv) Improvers. This review summarizes the features of SSc-ILD patients who are more likely to experience rapid progression of ILD, as well as those who are more likely not to experience ILD progression. Understanding the clinical, biological and radiographic factors that consistently predict ILD-related outcomes in SSc is central to our ability to recognize those patients who are at heightened risk for ILD progression. With new options available for treating patients with SSc-ILD, it is more important than ever to accurately identify patients who may derive the most benefit from aggressive SSc-ILD therapy. Early therapeutic intervention in patients with this progressive fibrosing phenotype may ultimately improve morbidity and mortality outcomes in patients with SSc-ILD.

Respiratory function in systemic sclerosis

Respiratory function in systemic sclerosis