Steroid-sparing agents in giant cell arteritis

Background: Giant cell arteritis is the commonest form of medium-to-large vessel vasculitis, requiring long-term corticosteroid therapy. The short- and long-term side effects of corticosteroids are many, including weight gain, psychological effects, osteoporosis, cardiometabolic complications, and infections. Materials and Methods: Various agents used in place of or in combination with corticosteroids to reduce corticosteroid-related side effects were reviewed. However, considerable variation in practice was identified giving unclear guidance. This review included the most recent evidence on methotrexate, mycophenolate mofetil, azathioprine, cyclophosphamide, abatacept, and tocilizumab Results and Discussion: Also discussed are encouraging results with tocilizumab in GCA patients. Amongst the agents available for steroid-sparing effects, tocilizumab demonstrated the most robust data and is consequently recommended as the agent of choice for steroid-sparing, for remission induction, remission maintenance, and treating relapsing and refractory cases of GCA.Published versio

Physical or occupational therapy use in systemic sclerosis: A Scleroderma Patient-centered Intervention Network cohort study

Item does not contain fulltextObjective: Systemic sclerosis (SSc) is characterized by significant disability due to musculoskeletal involvement. Physical and occupational therapy (PT/OT) have been suggested to improve function. However, the rate of PT/OT utilization has been shown to be low in SSc. We aimed to identify demographic, medical, and psychological variables associated with PT/OT use in SSc. Methods: Participants were patients with SSc enrolled in the Scleroderma Patient-centered Intervention Network Cohort. We determined the rate and indication of PT/OT use in the 3 months prior to enrollment. Multivariable logistic regression was used to identify variables independently associated with PT/OT utilization. Results: Of the 1,627 SSc patients included in the analysis, 23% used PT/OT in the preceding 3 months. PT/OT use was independently associated with higher education (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.12), having moderately severe small joint contractures (OR 2.09, 95% CI 1.45 - 3.03), severe large joint contractures (OR 2.33, 95% CI 1.14 - 4.74), fewer digital ulcerations (OR 0.70, 95% CI 0.51 - 0.95), and higher disability (OR 1.54, 95% CI 1.18 - 2.02) and pain (OR 1.04, 95% CI 1.02 - 1.06) scores. The highest rate of PT/OT utilization was reported in France (43%) and lowest in the USA (17%). Conclusion: Despite the potential of PT/OT interventions to improve function, less than 1 in 4 SSc patients enrolled in a large international cohort used PT/OT services in the last 3 months. Patients who utilized PT/OT had more severe musculoskeletal manifestations and higher pain and disability.9 p

Mental health care use and associated factors in systemic sclerosis: A Scleroderma Patient-Centered Intervention Network Cohort Study

Objective: Systemic sclerosis (SSc) has significant psychosocial implications. We aimed to evaluate the proportion of participants in a large international SSc cohort who used mental health services in a 3-month period and to evaluate demographic, psychological, and disease-specific factors associated with use. Methods: Baseline data of participants enrolled in the Scleroderma Patient-Centered Intervention Network Cohort were analyzed. We determined the proportion that used mental health services and the source of services in the 3 months prior to enrollment. Multivariable logistic regression was used to identify variables associated with service use. Results: Of the 2319 participants included in the analysis, 417 (18%) used mental health services in the 3 months prior to enrollment. General practitioners were the most common mental health service providers (59%), followed by psychologists (25%) and psychiatrists (19%). In multivariable analysis, mental health service use was independently associated with higher education (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.03-1.11), smoking (OR 1.06, 95% CI 1.02-1.11), being retired (OR 0.60, 95% CI 0.38-0.93), having limited SSc (OR 1.39, 95% CI 1.02-1.89), and having higher anxiety symptom scores (OR 1.04, 95% CI 1.03-1.06) and lower self-efficacy scores (OR 0.90, 95% CI 0.83-0.97). Variables not significantly associated included age, race, disease manifestations, depression symptom scores, and body image distress. Conclusion: About 18% of participants in a large international cohort received mental health services in a 3-month period, of whom the majority received these services from a general practitioner

The Scleroderma Patient-Centered Intervention Network Cohort: Baseline clinical features and comparison with other large scleroderma cohorts

Contains fulltext : 194824.pdf (publisher's version ) (Closed access)Objectives: The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts. Methods: Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. Results: Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN. Conclusion: Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants.9 p

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study

Background Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. Methods We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. Findings We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10–8; OR 1·19 [95% CI 1·12–1·26]) and VTN (rs704; p=2·75 × 10–9; OR 0·84 [0·79–0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10–8; OR 1·18 [1·12–1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15–3·82]; p=1·73 × 10–13). Interpretation We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis