Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Fertility preservation in women with vasculitis: experiences from the FertiPROTEKT network

Fertility preservation is not only important for malignant diseases but should also be offered to patients with autoimmune diseases (AID) like vasculitides, prior to cyclophosphamide therapy. No recommendations are available for patients with AID

Association of the ANCA-associated vasculitis (AAV) patient-reported outcome (AAV-PRO) questionnaire with established outcome measures in AAV

Objectives The ANCA-associated vasculitis (AAV) patient-reported outcome (AAV-PRO) questionnaire was developed to capture the impact of AAV and its treatment. We investigated the association of specific AAV-PRO domains with disease activity and extent, damage, depression, health-related quality of life and treatment. Methods In a prospective longitudinal study AAV-PRO, Beck’s depression inventory (BDI), Short Form 36 (SF36), BVAS and Vasculitis Damage Index (VDI) were completed at baseline (t1) and after 3–6 months (t2). In addition, patient data including diagnosis, therapies, relapses, and organ manifestations were recorded. Data were analyzed by t-tests and correlation-based regression analyses. Results 156 patients with AAV participated. The mean BVAS at the time of enrolment was 1.4 ± 3.74. Median AAV-PRO domain scores were higher in patients reporting “active disease” compared with patients reporting “in remission” (p< 0.001). In the correlation analyses all AAV-PRO domain scores correlated strongly with the BDI (all r ≥ 0.319, all p≤ 0.001) as well as all eight SF36 subdomains (all |r|≥0.267, all p≤ 0.001). The regression analyses showed that AAV-PRO domains were strongly predicted by BDI and SF36 domains (|β|≥0.240 for the strongest predictor of each domain). In the longitudinal comparison (t1/t2) there were no significant changes of the overall results. Conclusion Our data show convergent validity of all AAV-PRO subdomains with the established questionnaires BDI and SF-36. The AAV-PRO domains scores were not correlated with clinician derived instruments including the BVAS and VDI. Thus, we regard the AAV-PRO as a valuable addition that might complement traditional endpoints in clinical trials

Tocilizumab for the Treatment of Familial Mediterranean Fever—A Randomized, Double-Blind, Placebo-Controlled Phase II Study

Background: The purpose of this trial was to evaluate the effectiveness and safety of the IL-6 receptor antibody Tocilizumab (TCZ) in the treatment of Familial Mediterranean Fever (FMF). Methods: This was a randomized, double-blinded, placebo-controlled phase II trial in adult patients with active FMF and an inadequate response or intolerance to colchicine (crFMF). The physician’s global assessment of disease activity (PGA), based on a five-point scale for six symptoms, was used as a clinical score, which had to be >2 at screening, together with elevated c-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA) levels, to be eligible for inclusion. Patients were randomized 1:1 to either receive monthly TCZ or a placebo over a period of 24 weeks. The primary endpoint was the number of patients achieving an adequate response to treatment at week 16, defined as a PGA of ≤2 and normalized ESR or CRP and normalized SAA. Results: We randomized 25 patients with a median age of 31 years. At week 16, an adequate treatment response was achieved by two patients in the TCZ and none of the patients in the placebo arm (p = 0.089). SAA levels normalized with TCZ, but not with the placebo (p = 0.015). Conclusion: In this first randomized, placebo-controlled study in patients with active crFMF, more patients in the TCZ arm experienced a response to treatment in comparison to those receiving the placebo. As the prevention of amyloidosis is a major treatment goal in FMF, the normalization of SAA in TCZ-treated patients is essential. These findings have to be confirmed in a larger trial

Efficacy and Safety of Rituximab Treatment in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitides: Results from a German Registry (GRAID)

Objective. Rituximab (RTX) therapy is a treatment option in patients with refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We investigated the tolerability and clinical efficacy of RTX in a cohort of patients with refractory AAV. Methods. Clinical and safety data of patients with AAV treated with RTX were retrospectively assessed from the data of a German national registry. Results. In total, 58 patients were included in this analysis (50/58 with granulomatosis with polyangiitis; 8/58 with microscopic polyangiitis who received at least I cycle, 17 patients who received 2 cycles, and 3 patients who received 3 cycles of RTX). Response was classified as complete and partial in 22 (40%) and in 29 cases (52.7%), respectively. Four patients (7.3%) were classified as nonresponders. Conclusion. RTX was well tolerated with good clinical efficacy in patients with refractory AAV. (First Release Sept 15 2012; J Rheumatol 2012;39:2153-6; doi:10.3899/jrheum.120482

Histopathological and immunohistological findings in the myocardium of patients with systemic sclerosis and cardiac involvement.

<p>A: This image is representative for a biopsy with severe inflammation (grade 4), which is characterized by the presence of numerous CD3+ T lymphocytes and MHC II+ macrophages. In addition, a grade 3 fibrosis demonstrates severe cardiac remodeling in this patient. B: In the left picture, an overview of an endomyocardial biopsy is presented revealing two arterioles with pronounced changes of the architecture of the vessel walls including fibrosis. Immunohistological staining with SM-actin confirms a considerable hyperplasia of smooth muscle in the vessel. C: Fig 1C depicts normal heart tissue with Masson’s Trichrome staining on the left side from autopsy material of a patient, who died during an accident. Myocardial fibrosis (green area) was 2%. No inflammation (CD3+ T cells or MHC II+ cells) was detected within the myocardium, as shown in the immunohistochemistry on the right panel.</p