Investigating the trajectory of functional disability in systemic sclerosis: group-based trajectory modelling of the Health Assessment Questionnaire-Disability Index.

OBJECTIVES: To identify the trajectories and clinical associations of functional disability in systemic sclerosis (SSc). METHODS: Australian Scleroderma Cohort Study (ASCS) participants meeting ACR/EULAR criteria for SSc recruited within 5 years of disease onset, with ≥2 Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were included. Group based trajectory modelling (GBTM) was used to identify the number and shape of HAQ-DI trajectories. Between group comparisons were made using the chi-squared test, two-sample t-test or Wilcoxon rank-sum test as appropriate. Multiple logistic regression was used to identify features associated with trajectory group membership. Survival analyses were performed using Kaplan Meier and Cox proportional hazard modelling. RESULTS: We identified two HAQ-DI trajectory groups within 426 ASCS participants with incident SSc: low-stable disability (n=221, 52%), and high-increasing disability (n=205, 48%). Participants with high-increasing disability were older at disease onset, more likely to have diffuse SSc (dcSSc), cardiopulmonary disease, multimorbidity, digital ulcers, and gastrointestinal involvement (all p≤0.01), as was use of immunosuppression (p<0.01). Multimorbidity was associated with high-increasing trajectory group membership (OR3.1, 95%CI1.1-8.8, p=0.04); independently, multiple SSc features were also strongly associated including dcSSc (OR2.3, 95%CI1.3-4.2, p<0.01), proximal weakness (OR7.3, 95%CI2.0-27.1, p<0.01) and joint contractures (OR2.7, 95%CI1.3-5.3, p<0.01). High-increasing physical disability was associated with an almost two-fold increased risk of mortality (HR1.9, 95%CI1.0-3.8, p=0.05), and higher symptom burden. CONCLUSIONS: Two trajectories of functional disability in SSc were identified. Those with high-increasing functional disability had a distinct clinical phenotype and worse survival compared to those with low-stable functional disability. These data highlight the pervasive nature of physical disability in SSc, and its prognostic importance.

The burden and determinants of fatigue in incident and prevalent systemic sclerosis.

OBJECTIVES: To investigate the burden and clinical associations of fatigue in systemic sclerosis (SSc) as measured by FACIT-Fatigue scores. METHODS: Australian Scleroderma Cohort Study participants with ≥1 FACIT-Fatigue score were included. Participants were divided into those with incident SSc (≤5 years SSc duration at recruitment and FACIT-Fatigue score recorded within 5 years of disease onset) or prevalent SSc (first FACIT-Fatigue score recorded >5 years after SSc onset). Generalised estimating equations were used to model change in FACIT-Fatigue scores over time, expressed as an increasing (improving) or decreasing (worsening) score. RESULTS: Of 859 participants, 215 had incident SSc and 644 prevalent SSc. First-recorded FACIT-Fatigue scores were similar in those with incident (37 units, IQR 25-45.5) and prevalent SSc (36 units, IQR 23-44; p=0.17), as were lowest-ever recorded FACIT-Fatigue scores (incident 23 units; prevalent 22 units, p=0.75). In incident SSc, higher skin scores (regression coefficient (RC) -1.5 units, 95%CI -2.3 to -0.8), PAH (RC -8.2, 95%CI -16.5 to 0.1) and reduced left ventricular function (RC -10.6, 95%CI -18.3 to -2.8) were associated with more severe fatigue. In prevalent SSc, higher skin scores (RC -0.6, 95%CI -1.3 to 0), gastrointestinal symptoms (RC -6.6, 95%CI -9.0 to -4.2), hypoalbuminaemia (RC -2.8, 95%CI -5.0 to -0.7), BMI<18.5kg/m2 (RC -6.3, 95%CI -10.3 to -2.2), raised CRP (RC -3.1, 95%CI -4.7 to -1.5), and anaemia (RC -1.7, 95%CI -3.5 to 0.1) were associated with more severe fatigue. CONCLUSIONS: The burden of fatigue is substantial in both incident and prevalent SSc. Cardiopulmonary and gastrointestinal involvement are associated with worse fatigue.

Predictive accuracy of the ASIG algorithm in a prospective systemic sclerosis cohort undergoing annual screening for pulmonary arterial hypertension.

The Australian Scleroderma Interest Group (ASIG) algorithm for screening pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) requires only respiratory function tests and serum N-terminal pro-brain natriuretic peptide as first-tier tests, and is recommended in international guidelines. In this communication, we present the findings of the application of the ASIG screening algorithm to a Singaporean cohort undergoing prospective annual screening for PAH, which shows a high negative predictive value. The ASIG algorithm may offer an alternative to more complex and costly SSc-PAH screening algorithms.

"It means almost forgetting that you've got a disease": An OMERACT study to define independence in the context of rheumatoid arthritis remission from the patient perspective.

AIMS: Our previous work identified pain, fatigue, and independence as missing from the ACR/EULAR rheumatoid arthritis (RA) remission criteria from the patient perspective. Validated measures exist for pain and fatigue, but not for independence. As a first step towards developing such a measure, this study aimed to understand 'Independence' in the context of RA remission from the patient perspective. METHODS: International qualitative research study comprising five focus groups of 19 participants with RA. Data were analysed using reflexive thematic analysis. RESULTS: Five overarching themes were identified, underpinned by a construct of "stages of independence". Independence means at least being 'physically and functionally able' but may go beyond this and enable 'participation beyond function', 'cognitive independence', and 'having or taking control'. There was no agreement on whether assistance is an aid to independence or undermines ability to achieve independence ('assistance is complicated'). The construct "Stages of independence" acknowledges that Independence may mean different things to different patients and there may be other factors beyond disease activity that hold patients in each of these stages. CONCLUSION: These novel data suggest a desirable definition of independence includes full active participation without the need to consider or work around disease activity, and cognitive independence from thoughts of RA. Independence in RA remission is a complex concept and next steps will be to seek patient and professional agreement on the most important issues raised in these focus groups to take forward to developing a measure for independence in the context of RA remission from the patient perspective.

Tocilizumab use in giant cell arteritis: comparing Pharmaceutical Benefits Scheme eligible and ineligible cases in South Australia.

Tocilizumab (TCZ) is increasingly used as a steroid-sparing agent in giant cell arteritis (GCA), but there are strict Pharmaceutical Benefits Scheme (PBS) restrictions for its use in Australia. Patients who do not meet the PBS criteria can obtain TCZ through public hospital individual patient use (IPU) schemes which may not be universally accessible. We compared patients receiving IPU-approved TCZ with patients receiving PBS-subsidised TCZ and found IPU approvals were granted mainly for visual loss, a serious complication of GCA, in patients who otherwise failed to meet PBS criteria. Further studies demonstrating that TCZ is comparatively more effective than prednisolone monotherapy, as well as cost-effective, are needed to substantiate the rationale for expanding PBS approval criteria.

Pharmacokinetic-pharmacodynamic modelling and simulation of methotrexate dosing in patients with rheumatoid arthritis.

AIMS: To develop a non-linear mixed-effects population pharmacokinetic and pharmacodynamic (PK-PD) model describing the change in the concentration of methotrexate polyglutamates in erythrocytes (ery-MTX-PGn with "n" number of glutamate, representing PK component) and how this relates to modified 28-joint Disease Activity Score incorporating erythrocyte sedimentation rate (DAS-28-3) for rheumatoid arthritis (RA), representing PD component. METHODS: An existing PK model was fitted to data from a study consisting of 117 RA patients. The estimation of population PK-PD parameters was performed using stochastic approximation expectation maximisation algorithm in Monolix 2021R2. The model was used to perform Monte Carlo simulations of a loading dose regimen (50mg subcutaneous methotrexate as loading doses, then 20mg weekly oral methotrexate) compared to a standard dosing regimen (10mg weekly oral methotrexate for 2 weeks, then 20mg weekly oral methotrexate). RESULTS: Every 40 nmol/L increase in ery-MTX-PG3-5 total concentration correlated with 1-unit reduction in DAS-28-3. Significant covariate effects on the therapeutic response of methotrexate included the use of prednisolone in the first 4 weeks (positive use correlated with 25% reduction in DAS-28-3 when other variables were constant) and patient age (every 10-year increase in age correlated with 3.4% increase in DAS-28-3 when other variables were constant). 4 methotrexate loading doses led to a higher percentage of patients achieving a good/moderate response compared to the standard regimen (Week 4: 87.6% vs. 39.8%; Week 10: 64.7% vs. 57.0%). CONCLUSIONS: A loading dose regimen was more likely to achieve higher ery-MTX-PG concentration and better therapeutic response after 4 weeks of methotrexate treatment.

Development and Initial Validation of the Novel Scleroderma Clinical Trials Consortium Activity Index.

OBJECTIVE: Accurate measurement of disease activity in systemic sclerosis (SSc) remains a significant clinical challenge. The Scleroderma Clinical Trials Consortium (SCTC) convened an Activity Index Working Group (WG) to develop a novel measure of disease activity (SCTC-AI). METHODS: Using consensus methodology, we developed a conceptual definition of disease activity. Literature review and expert consensus generated provisional SCTC-AI items, which were reduced by Delphi survey. Provisional items were weighted against a combined endpoint of morbidity and mortality, using time-dependent Cox proportional hazards regression analysis of the Australian Scleroderma Cohort Study (ASCS) (n=1,254). External validation of the SCTC-AI was performed using data collected from 1,103 Canadian Scleroderma Research Group Study participants. RESULTS: Disease activity in SSc was defined using consensus methodology as 'aspects of disease that are reversible, or can be arrested, with time and, or effective therapy'. One-hundred and forty-one provisional SCTC-AI items were generated and reduced using 3 rounds of Delphi survey and statistical reduction and weighting, against mortality and quality of life measures, yielding a final 24-item index with a maximum possible score of 140. Survival analysis in an external cohort showed a graded relationship between disease activity scores and survival (p<0.01). CONCLUSION: We present a novel instrument to quantify the burden of disease activity in SSc. We have employed a rigorous consensus-based process in combination with data-driven methods, to develop an instrument that has face, content and criterion validity. Further work is required to fully validate and confirm the construct and discriminative validity of the SCTC-AI.

Prognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis.

OBJECTIVES: To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. RESULTS: Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0-4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0-11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6-7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4-9.2, p < 0.01) was also seen in those with impaired LV-GLS. CONCLUSIONS: Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.

Outcomes of Patients With Diffuse Systemic Sclerosis Eligible for Autologous Stem Cell Transplantation Treated With Conventional Therapy.

OBJECTIVE: The study objective was to determine the event-free survival (EFS) of Australian patients with diffuse cutaneous systemic sclerosis (dcSSc) who met eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomized controlled trials but were not treated with ASCT. METHODS: Patients who met inclusion criteria for the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) and Scleroderma: Cyclophosphamide Or Transplantation (SCOT) trials were identified from the multicenter Australian Scleroderma Cohort Study (ASCS). EFS (survival without cardiac, renal, or pulmonary failure or death) at 4 years was assessed. ASCS patients who had already undergone transplantation were excluded from analysis. RESULTS: Of the 492 patients with dcSSc in the ASCS, 56 met ASTIS inclusion criteria for ASCT (56 of 492 [11.4%]) and 30 met SCOT inclusion criteria (30 of 492 [6.1%]). An additional 11 patients met ASTIS or SCOT inclusion criteria, but they were excluded due to severe organ manifestations. EFS at 4 years in ASCS patients meeting ASTIS inclusion criteria was 83.3% and in ASCS patients meeting SCOT inclusion criteria was 81.2%. EFS at 4 years in ASCS patients who met ASTIS and SCOT inclusion but also exclusion criteria was 46.7% and 45.7%, respectively. CONCLUSION: ASCS patients meeting ASTIS and/or SCOT inclusion criteria who were not treated with ASCT have similar EFS at 4 years as patients receiving ASCT and better EFS than those receiving cyclophosphamide in the ASTIS and SCOT trials. This may reflect confounders unable to be controlled for, including survivor bias, but may also reflect improved standard of care for dcSSc over time.

Frequency and implications of malnutrition in systemic sclerosis.

OBJECTIVES: To quantify the frequency and impact of malnutrition in systemic sclerosis (SSc), as diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria, based on weight loss, body mass index (BMI) and muscle atrophy. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 concurrent weight and height measurement were included. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Multivariable logistic regression models were used to establish the determinants of malnutrition diagnosis. Kaplan-Meier and Cox proportional hazard models were used for survival analyses, based on malnutrition diagnosis, and individual GLIM criteria (% weight loss, BMI thresholds and presence of muscle atrophy). RESULTS: In this study of 1903 participants, 43% were diagnosed with malnutrition according to GLIM criteria, of whom 33% had severe malnutrition. Participants diagnosed with malnutrition were older, and more likely to have dcSSc, higher SSc severity scores and RNA polymerase-3 positivity. Gastrointestinal (GI) involvement, multimorbidity, cardiopulmonary disease, raised inflammatory markers, hypoalbuminaemia and anaemia were more common in malnourished participants (p< 0.01). Multimorbidity (OR1.6, 95%CI1.2-2.0, p< 0.01), pulmonary arterial hypertension (OR2.1, 95%CI1.4-2.0, p< 0.01) and upper GI symptoms (OR1.6, 95%CI1.3-2.0, p< 0.01) were all associated with malnutrition.Health-related quality-of-life (HRQoL) and physical function were poorer in malnourished participants. Survival was worse in those with malnutrition after adjusting for age, sex and dcSSc (HR 1.4, 95%CI1.1-1.7, p< 0.01). CONCLUSIONS: Malnutrition is common in SSc and confers poorer survival, HRQoL and physical function.

Predictors and prognosis of pulmonary hypertension complicating interstitial lung disease in systemic sclerosis.

OBJECTIVE: To identify those with concurrent pulmonary hypertension (PH) and interstitial lung disease (ILD) in systemic sclerosis (SSc) and determine their disease severity, therapeutic approach, and survival. METHODS: Consecutive SSc patients enrolled in the Australian Scleroderma Cohort Study (ASCS) who were diagnosed on right heart catherisation with pulmonary hypertension were included. Logistic regression was used to determine the associations of ILD with PH hemodynamic parameters and therapeutic approach. Kaplan-Meier survival curves were used to estimate survival. RESULTS: Of 1,883 SSc patients, 164 (8.7%) developed incident PH over a median follow up of 4.3 (1.7-7.9) years. Of these, 43.9% had concurrent ILD at PH diagnosis (PH-ILD) and 56.1% had Group 1 PAH. Extensive ILD was present at PH diagnosis in 40.3%. Despite these distinct PH cohorts, a similar frequency of each PH cohort was treated with vasodilatory therapy at PH diagnosis, regardless of the presence or severity of ILD. The majority (87.5%) of those with extensive ILD and PH received upfront vasodilatory therapy at PH diagnosis with no difference in its tolerability or therapy cessation compared with Group 1 PAH. Although vasodilator therapy was not associated with a survival advantage in those with extensive ILD, its use was associated with an improvement in symptoms, physical function, and quality of life (QoL). CONCLUSION: Despite vasodilator therapy, survival in SSc-PH is poor, with the presence of concurrent ILD associated with worse survival. Although vasodilator therapy commenced at PH diagnosis does not portray an improved survival in PH with extensive ILD, it appears well tolerated and may improve symptoms, physical function, and QoL.

Quantifying the Need for Specialist Palliative Care Management in Patients With Systemic Sclerosis.

OBJECTIVE: The importance of early integration of palliative care in the management of complex multisystem diseases has been recognized. In this study, we aimed to quantify the need for specialist palliative care in patients with systemic sclerosis (SSc). METHODS: Using data from 875 patients enrolled in the Australian Scleroderma Cohort Study, we defined the need for palliative care as a high symptom burden at two or more consecutive study visits, at ≥50% of overall study visits, or at the study visit immediately before death. Symptoms of interest included breathlessness, fatigue, pain, depression, anxiety, constipation, and diarrhea. Logistic regression analyses evaluated the association between individual symptoms and SSc manifestations. Linear regression analysis evaluated the relationship between palliative care needs and quality of life (QoL) and function. RESULTS: Almost three-quarters of patients (72.69%) met the threshold for specialist palliative care needs. Severe fatigue (54.17%) was most common, followed by breathlessness (23.66%) and severe constipation (21.14%). Concurrent severe symptoms were frequently observed. Severe breathlessness (coefficient [coef] -7.95, P < 0.01) and pain (coef -7.70, P < 0.01) were associated with the largest reductions in physical QoL. Severe mood symptoms were associated with the greatest reduction in mental QoL (coef -12.91, P < 0.01). Severe pain (coef 0.56, P < 0.01), breathlessness (coef 0.49, P < 0.01), and mood symptoms (coef 0.40, P < 0.01) had a significant impact on function. CONCLUSION: SSc is frequently associated with multiple severe symptoms that may be amenable to palliative care intervention. Given the strong association between symptom burden and impaired QoL targeted, effective symptom management in parallel with standard-of-care treatments may improve overall patient outcomes.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

OBJECTIVE: Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time. METHODS: We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score. RESULTS: At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up. CONCLUSION: The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines.

Prognostic modeling in early rheumatoid arthritis: reconsidering the predictive role of disease activity scores.

OBJECTIVE: In this prospective cohort study, we provide several prognostic models to predict functional status as measured by the modified Health Assessment Questionnaire (mHAQ). The early adoption of the treat-to-target strategy in this cohort offered a unique opportunity to identify predictive factors using longitudinal data across 20 years. METHODS: A cohort of 397 patients with early RA was used to develop statistical models to predict mHAQ score measured at baseline, 12 months, and 18 months post diagnosis, as well as serially measured mHAQ. Demographic data, clinical measures, autoantibodies, medication use, comorbid conditions, and baseline mHAQ were considered as predictors. RESULTS: The discriminative performance of models was comparable to previous work, with an area under the receiver operator curve ranging from 0.64 to 0.88. The most consistent predictive variable was baseline mHAQ. Patient-reported outcomes including early morning stiffness, tender joint count (TJC), fatigue, pain, and patient global assessment were positively predictive of a higher mHAQ at baseline and longitudinally, as was the physician global assessment and C-reactive protein. When considering future function, a higher TJC predicted persistent disability while a higher swollen joint count predicted functional improvements with treatment. CONCLUSION: In our study of mHAQ prediction in RA patients receiving treat-to-target therapy, patient-reported outcomes were most consistently predictive of function. Patients with high disease activity due predominantly to tenderness scores rather than swelling may benefit from less aggressive treatment escalation and an emphasis on non-pharmacological therapies, allowing for a more personalized approach to treatment. Key Points • Long-term use of the treat-to-target strategy in this patient cohort offers a unique opportunity to develop prognostic models for functional outcomes using extensive longitudinal data. • Patient reported outcomes were more consistent predictors of function than traditional prognostic markers. • Tender joint count and swollen joint count had discordant relationships with future function, adding weight to the possibility that disease activity may better guide treatment when the components are considered separately.

IDH-mutant myeloid neoplasms are associated with seronegative rheumatoid arthritis and innate immune activation.

ABSTRACT: High prevalence of IDH mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity, and proinflammatory microenvironment suggests causative association between IDH mutations and seronegative RA. Our findings merit investigation of IDH inhibitors as therapeutics for seronegative IDH-mutated RA.

Proximal weakness and creatine kinase elevation in systemic sclerosis: Clinical correlates, prognosis and functional implications.

OBJECTIVES: To determine the frequency, clinical correlates and implications of clinical evidence of muscle disease in systemic sclerosis (SSc). METHODS: Australian Scleroderma Cohort Study participants with ≥1 creatine kinase (CK) and proximal power assessment were subdivided according to presence of proximal weakness (PW: proximal muscle power<5/5) and CK elevation(≥140IU/L). Participants were assigned to one of four groups: concurrent PW&CK elevation, PW alone, CK elevation alone or neither. Between-group comparisons were made with chi-squared, ANOVA or Kruskal-Wallis tests. Survival analysis was performed using time-varying-covariate Cox regression modelling. Longitudinal data were modelled using multinomial logistic and linear regression. RESULTS: Of 1786 participants, 4 % had concurrent PW&CK elevation, 15 % PW alone, 24 % CK elevation and 57 % neither. Participants with PW&CK elevation displayed a severe, inflammatory SSc phenotype, with more frequent dcSSc(p < 0.01), tendon friction rubs(p < 0.01), synovitis(p < 0.01) and digital ulceration(p = 0.03). Multimorbidity(p < 0.01) and cardiopulmonary disease, including ischaemic heart disease(p < 0.01) and pulmonary arterial hypertension(p < 0.01), were most common in those with PW, with and without CK elevation. Men with anti-Scl70 positivity most frequently had CK elevation alone, without other significant clinical differences. Multivariable modelling demonstrated 3.6-fold increased mortality in those with PW&CK elevation (95 %CI 1.9-6.6, p < 0.01) and 2.1-fold increased mortality in PW alone (95 %CI 1.4-3.0, p < 0.01) compared to those without PW or CK elevation. CK elevation alone conferred better survival (HR 0.7, 95 %CI 0.4-1.1, p = 0.09) compared to those with no PW or CK elevation. PW regardless of CK elevation was associated with impaired physical function, with reduced six-minute-walk-distance (p < 0.01), higher HAQ-DI scores (p < 0.01) and increased patient-reported dyspnoea (p = 0.04). CONCLUSION: Clinical features of myopathy are highly prevalent in SSc, affecting almost half of our study cohort. Detection of PW and elevated CK alone, even without imaging or histopathological identification of SSc-myopathy, identified important clinical associations and are associated with poorer function and overall prognosis.

Patients' perspectives on systemic sclerosis-related Raynaud's phenomenon in the feet: A qualitative study from the OMERACT Foot and Ankle Working Group.

OBJECTIVE: To explore, from patients' perspectives, the symptoms and impact of Raynaud's phenomenon (RP) on the feet of patients with systemic sclerosis (SSc-RP), and to identify which foot-related domains are important to patients. METHODS: Forty participants (34 women) with SSc-RP took part in one of six focus groups held in the United Kingdom or United States. Participants were purposively sampled to ensure diversity in disease type, duration, and ethnicity. The topic guide included questions on RP impact, self-management, and treatment expectations. Qualitative content analysis was employed to identify key concepts in the data relating to foot-specific symptoms and their impact. Themes were organized by corresponding domains of potential importance. RESULTS: Twenty-eight participants (70 %) reported experiencing RP in their feet. Five themes were identified corresponding to domains of potential importance: temperature changes, pain, cramping and stiffness, numbness, and color changes. These issues negatively affected participants' lives, impairing walking, driving, and socializing, and causing issues with footwear and hosiery. CONCLUSIONS: This large qualitative study exploring the experiences of patients with SSc-RP in the feet identified several key domains of high importance to patients. SSc-RP is common in the feet, presents in several patterns, and impacts multiple aspects of patients' lives. These findings indicate where future foot-specific interventions for RP could be targeted. Findings from this study improve understanding of what domains are important to patients with SSc-RP affecting the feet and will contribute to the development of a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases.

Inflammatory Arthritis in Systemic Sclerosis: Its Epidemiology, Associations, and Morbidity.

OBJECTIVE: To describe the epidemiology, associations, and impact of inflammatory arthritis (IA) in systemic sclerosis (SSc). METHODS: Patients with SSc prospectively enrolled in the Australian Scleroderma Cohort Study were included. IA was defined clinically as the presence of synovitis on examination. Logistic regression was used to determine the associations of IA with SSc manifestations and serological parameters. Patient-reported outcome measures were used to capture physical function and health-related quality of life (HRQoL). RESULTS: IA was a common SSc manifestation affecting one-third (33.3%) of patients over a median follow-up of 4.3 (1.7-8.4) years. Associations of IA included diffuse SSc (odds ratio [OR] 1.33, 95% confidence interval [95% CI] 1.01-1.74, P = 0.042), concurrent musculoskeletal manifestations (joint contractures and tendon friction rubs, OR 1.70, 95% CI 1.34-2.15, P < 0.001); myositis (OR 2.11, 95% CI 1.39-3.20, P < 0.001), and sicca symptoms (OR 1.57, 95% CI 1.14-2.16, P = 0.006), whereas IA was negatively associated with pulmonary arterial hypertension (OR 0.52, 95% CI 0.35-0.78, P = 0.002). Neither the presence of rheumatoid factor nor U1 small nuclear RNP were associated with IA (OR 1.13, 95% CI 0.88-1.44, P = 0.331, OR 1.46, 95% CI 0.89-2.39, P = 0.129 respectively). Positive anticyclic citrullinated protein antibodies, although at low frequency, were more common in those with IA compared with those without IA (7.5% vs 1.5%, P < 0.001). IA was associated with significantly lower HRQoL score (P < 0.001) and more physical disability than in those without IA (P < 0.001). CONCLUSION: IA is a common disease manifestation that is more frquently seen in diffuse disease. IA is associated with poor HRQoL and physical disability. Further research is needed into the effective management of IA in SSc.

Outcomes of proximal humerus fractures in children: a retrospective cohort study.

OBJECTIVE: Paediatric proximal humerus fractures (PHFs) have historically been treated non-operatively. However, the management of severely displaced PHFs in older children has been debated over the years, with contemporary studies advocating for surgery. The purpose of this study was to review the outcomes of a cohort of paediatric patients treated for a PHF to guide management of future paediatric PHFs. METHODS: The records of the Women's and Children's Hospital in South Australia were reviewed to identify paediatric PHFs occurring between 1 January 2010 and 1 June 2020. Participants completed the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), the Shoulder Pain and Disability Index, and the Paediatric Outcomes Data Collection Instrument via phone interview. Participants' shoulder range-of-motion was assessed via telehealth using Zoom. Multivariable logistic regression was used to identify patient and clinical variables that were associated with a poorer outcome. RESULTS: Of 307 patients contacted, 125 participated. Forty-six patients met the definition of a poorer clinical outcome, defined as a QuickDASH score of ≥2. Fractures of greater severity were predictive of a poorer outcome, and patients aged ≥12 years old at the time of injury had higher total QuickDASH scores. The findings did not suggest that these subgroups of patients have superior outcomes if treated surgically. CONCLUSION: The majority of paediatric PHFs have an acceptable clinical outcome, irrespective of treatment methodology. Multicentre prospective studies are required to establish the indications for surgery for adolescent patients with severely displaced PHFs.