Background: Systemic sclerosis (SSc) is a multiorgan disease, that frequently affects the skin and involves the lung in up to 70 percent of cases with a 10 years mortality rate in SSc up to 50 percent. B cell-depleting therapy with rituximab (RTX) seems to be effective in the treatment of SSc, but data from randomized controlled trials (RCTs) are missing and there is no consensus on frequency and dosage of RTX in SSc. [1-3] Objectives: We aimed to assess the long-term efficacy and safety of quarterly administered RTX in SSc. Methods: Retrospective analyses of 40 consecutive systemic sclerosis patients suffering from interstitial lung disease and progredient skin involvement treated with rituximab twice within 14 days every three months from 2010-2020. Of RTX-treated patients 42.5 % were treated with RTX monotherapy and 47.5 with RTX in combination with other immunosuppressants. The patients' fulfilled the LeRoy and the ACR/EULAR Criteria for SSc. (4) Modified Rodnan skin score (mRSS), lung function test results, laboratory values including serum immunoglobulin (IgG, IgA, IgM) concentrations.[5] The clinical parameters are included in the EScSGAI and have been documented over time.[6] (Figure 1) Results: In total 40 SSc patients received RTX as described above over a median time of 3.9 years (1-10 years). A significant improvement in median mRSS (baseline: 19, month 24: 16, p<0.001), as well as a stable predicted forced vital capacity (FVC) were observed from baseline to month 24. There were no new or unexpected safety signals especially regarding treatment-related infectious adverse events. Immunoglobuline concentrations stayed within the normal range and specific antibodies to pneumococcal polysaccharides were preserved despite of long term B cell depleting therapy. During the observation period of up to ten years none of the patients died. (A) European Scleroderma Study Group Activity Index, (B) modified Rodnan Skin Score (mRss), (C) forced vital capacity (FVC) in percent predicted, and (D) diffusing lung capacity of carbonmonoxide (DLCO) in percent during RTX treatment. The number of patients treated is indicated by n, the duration of treatment on the x-axis by months. Median + 95%CI Significance was calculated using paired Wilcoxon Test. Conclusion: Conclusion: SSc can be effectively and safely treated by 3-monthly, low-dose RTX. Controlled, randomized studies are needed to validate the advantage of continuous B cell depletion by 3-monthly low dose RTX application compared to other application intervals. REFERENCES: [1] Katsumoto TR, Whitfield ML, Connolly MK. The pathogenesis of systemic sclerosis. Annu Rev Pathol. 2011 Feb 28;6:509–37. [2] Moazedi-Fuerst FC, Kielhauser SM, Brickmann K, Hermann J, Lutfi A, Meilinger M, et al. Rituximab for systemic sclerosis: arrest of pulmonary disease progression in five cases. Results of a lower dosage and shorter interval regimen. Scand J Rheumatol [Internet]. 2014 Jan [cited 2015 Feb 25];43(3):2. [3] Maher TM, Tudor VA, Saunders P, Gibbons MA, Fletcher S V, Denton CP, et al. Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med. 2022 Jan; [4] van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum [Internet]. 2013 Nov [cited 2016 Mar 23];65(11):2737–47. [5] Venhoff N, Effelsberg NM, Salzer U, Warnatz K, Peter HH, Lebrecht D, et al. Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides. PLoS One. 2012 May 21;7(5). [6] Valentini G, Bencivelli W, Bombardieri S, D'Angelo S, Della Rossa A, Silman AJ, et al. European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria. Ann Rheum Dis [Internet]. 2003 Sep [cited 2018 Oct 10];62(9):901–3. Acknowledgements: NIL. Disclosure of Interests: None declared.

Background Golimumab has shown clinical efficacy and tolerability within its clinical trial program. No systemic outcome data regarding patient-reported outcomes and health economic parameters reflecting the real world use of golimumab in Austria are currently available. Methods Go Active is a prospective, non-interventional, multi-centre study in Austria. The impact of golimumab therapy on work productivity and activity (WPAI) and quality of life (RAQoL for RA patients, AsQoL for axSpA patients, PsAQoL for PsA patients) is assessed by using patient reported outcomes. Patients (target recruitment: n=320) are followed up to 2 years. For the current interim analysis (data cut-off: 18DEC2017) changes in the primary endpoint from baseline to month 3 were analysed in 167 patients. Results 167 patients are included in the current analysis (74 patients with RA, 49 patients with axSpA, and 44 patients with PsA). At study entry, most patients were biological-naïve and employed. Median age at registration was 52 years (patients with RA: 57 years, patients with axSpA: 41 years, and patients with PsA: 44 years). Almost 2/3 of patients were female (84% of patients with RA, 37% patients with axSpA, and 55% of patients with PsA). Most patients were biological-naïve at study entry (77% of all patients, 73% of patients with RA, 80% of patients with axSpA, and 82% of patients with PsA). 42% of patients were not employed (58% of patients with RA, 29% of patients with axSpA, and 30% of patients with SpA); 14% due to incapacity for work (12% of patients with RA, 21% of patients with axSpA, and 16% of patients with SpA) and 54% due to age-related pension (60% of patients with RA, 21% of patients with axSpA, and 69% of patients with SpA). Most of the patients, who worked for pay, worked full time. 159 of all patients and 66 of employed patients completed the WPAI questionnaire at baseline and after 3 months. Overall work productivity improved by −33 (−40 for patients with RA, and −31 for patients with axSpA and PsA) and activity impairment by −30 (−40 for patients with RA and axSpA, and −20 for patients with PsA; figure 1). Quality of life improved by −5 for patients with axSpA and PsA, and by −7 for patients with RA.Abstract FRI0108 – Figure 1 WPAI questionnaire – Changes from baseline after 3 months of golimumab treatment Conclusions This interim analysis shows that golimumab treatment is effective in improving work productivity, daily activities as well as quality of life already within the first 3 months of treatment in RA, axSpA and PsA patients. Disclosure of Interest C. Dejaco Consultant for: Consulting fees from Merck Sharp and Dohme, Paid instructor for: Remuneration form Merck Sharp and Dohme, Speakers bureau: Merck Sharp and Dohme, T. Mueller: None declared, O. Zamani: None declared, U. Kurtz: None declared, S. Egger: None declared, J. Resch-Passini: None declared, A. Totzauer: None declared, W. Eisterer: None declared, B. Yazdani-Biuki: None declared, T. Schwingenschloegl: None declared, P. Peichl: None declared, A. Kraus: None declared, G. Naerr Employee of: Merck Sharp and Dohme Ges.m.b.H, V. Rickert Employee of: Merck Sharp and Dohme Ges.m.b.H

OBJECTIVESAs interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients is associated with increased mortality due to loss of diffusion capacity and pulmonary hypertension, regular screening for structural abnormalities of the lung is advised. In addition to standard radiological examination with computed x-ray tomography, ultrasound of the lung could allow non-invasive and radiation-free structural monitoring of the lung. The objective of this study was to test the frequency of abnormalities in lung sonography in patients with RA who did not have clinical signs or symptoms of lung disease.METHODSIn a prospective study of 64 consecutive patients with rheumatoid arthritis and 40 healthy volunteers, we screened the pleura and the pulmonary parenchyma for sonographic abnormalities. All RA patients underwent high resolution computer tomography of the lung.RESULTS28% of RA patients showed pleural nodules or B-line phenomena. In these patients, CT scans showed signs of incipient interstitial lung disease. Lung sonography showed sporadic abnormalities in 7% of the healthy controls.CONCLUSIONSTransthoracic ultrasound of the lung is an inexpensive and safe tool to screen patients with RA for incipient pulmonary structural changes.

Objective. Sera front patients with lymphoid neoplasias contain rheumatoid factors (RF) so often that RF are of limited use for diagnosing arthritis in lymphoma patients. Antibodies against citrullinated peptides (ACPA) might be helpfill in distinguishing between true RA and rheumatoid factor-positive conditions with arthritis. We compared the specificity of RF and of ACPA for the diagnosis of RA in patients with B-cell chronic lymphocytic leukemia (CLL).Methods. One hundred and seven patients with CLL without any clinical signs of arthritis and five patients with RA and concomitant CLL were included in the investigation. Serum samples were tested for RF-isotypes IgM, IgG and IgA. ACPA were determined with an ELISA that detects anti-cyclic citrullinated peptide (aCCP) antibodies.Results. RF well beyond the cut-off levels were detected in 50% of the CLL-patients without RA. The isotype distribution was 41% IgM-RF, 20% IgG-RF and 3% IgA-RF. None of the 107 CLL patients without arthritis had aCCP antibodies. Within the whole cohort of CLL patients the specificity for the diagnosis of RA was 100% for aCCP antibodies and 59% for IgM-RF.Conclusion. Only aCCP antibodies hut not IgM-, IgG- or IgA-RF are useful for the diagnosis of RA in patients with CLL.

Rheumatoid arthritis (RA) is a chronic inflammatory disease resulting in inflammation of the synovial lining and destruction of the adjacent bone and cartilage. Although the initiating event of RA is still unknown, recent research has demonstrated the importance of the increased production of tumour necrosis factor (TNF) α in the perpetuation of the inflammatory process of this disease. Targeting this molecule with soluble receptors—that is, etanercept, or antibodies, like infliximab or adalimumab, a new class of highly effective antirheumatic drugs has been developed. Unfortunately, not all patients respond sufficiently to TNF blockade or become unresponsive, and therefore …

Breast cancer is the most frequently diagnosed cancer among women in western countries and bone metastases of breast cancer cause significant morbidity. G proteins are important components of a multitude of transmembrane receptors and are involved in the regulation of intracellular signaling pathways such as parathormone receptors 1 and 2 (PTH1 and 2), extracellular calcium-sensing receptor, the calcitonin receptor and the OPG/RANKL-system. A common polymorphism in the gene encoding the G protein beta 3-subunit, GNB3 825C > T, has been linked to increased G protein activation. To analyse the role of this polymorphism in bone metastasis of breast cancer, we determined GNB3 825C > T genotypes in 500 female breast cancer patients. According to breast cancer staging, patients were divided in three groups, representing patients without metastases (n = 250), those with metastases other than bone (n = 117), and those with bone metastasis (n = 133). Frequency of the GNB3 825 TT genotype was significantly lower among patients with bone metastases (3.1%) than among those with other metastases (12.8%; P = 0.004) or no metastases (13.3%; P < 0.001). In a Cox regression analysis, relative risk of the GNB3 TT genotype for bone metastasis was 0.22 (95% CI 0.08-0.61; P = 0.004) for bone metastasis. We conclude that the homozygous GNB3 825 TT genotype may be protective against development of bone metastasis in breast cancer patients. The precise mechanism for this remains to be determined, but could be due to a direct involvement of G protein-coupled receptors in bone metabolism.

Cyclooxygenase-2 (COX-2) is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. The gene for COX-2, designated as PTGS2, carries a common polymorphism at position 8473 in the 3'-untranslated region (PTGS2 8473T>C), which has been associated with susceptibility to malignant disease. To investigate the role of this polymorphism for breast cancer, we determined the prevalence of PTGS2 genotypes in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Homozygous carriers of the 8473-CC genotype were more frequent among patients (12.4%) than among controls (6.6%; P = 0.002). The odds ratio for carriers of this genotype for breast cancer was 2.1 (95% confidence interval, 1.3-3.3). Among patients, estrogen receptor positivity was less frequent among carriers of a CC genotype (63.9%) than among carriers of a TT or TC genotype (76.9%; P = 0.028). Tumor size, histologic grade, presence of primary lymph node metastases, progesterone receptor positivity, or age at diagnosis were not associated with PTGS2 genotypes. We conclude that the homozygous PTGS2 8473-CC genotype may be associated with breast cancer risk.

Background:  The traditional treatment for obesity which is based on a reduced caloric diet has only been partially successful. Contributing factors are not only a poor long‐term dietary adherence but also a significant loss of lean body mass and subsequent reduction in energy expenditure. Both low‐fat, high‐carbohydrate diets and diets using low‐glycaemic index (GI) foods are capable of inducing modest weight loss without specific caloric restriction. The purpose of this study was to investigate the feasibility and medium‐term effect of a low‐fat diet with high (low GI) carbohydrates on weight loss, body composition changes and dietary compliance.

OBJECTIVE:To determine the effect on the humoral immune system of long term treatment of patients with RA with etanercept. METHODS:12 consecutive patients with seropositive RA treated with etanercept were studied and followed up for 9 months. Clinical efficacy of treatment was evaluated using the 28 joint count Disease Activity Score (DAS28). Serum samples were collected at baseline and after 9 months and serum immunoglobulin, RF isotypes, and anti-cyclic citrullinated peptide (aCCP), antinuclear, nucleosome, and dsDNA antibodies determined. For comparison 7 patients with seropositive RA treated with adalimumab were studied. RESULTS:DAS28 decreased significantly after the first month and then was constant for the whole study (5.7 (0.3) v 3.8 (0.2), p< or=0.000). Serum IgA-RF and IgG-RF increased significantly after 9 months' etanercept treatment (mean (SEM) IgA-RF rose from 19.5 (4.8) to 30.5 (5.9) IU/ml, p< or=0.01; IgG-RF from 20.6 (8.1) to 33.8 (11.5) IU/ml, p< or=0.04). Serum levels of total immunoglobulin and specific autoantibodies remained unchanged during the study. In patients treated with adalimumab, no significant changes in serum levels of RF isotypes and aCCP antibodies were seen. CONCLUSION:Etanercept, although effective in treating the clinical symptoms of RA, seems to have a pivotal effect on RF-producing B cells either directly or indirectly.

Purpose: The matrix metalloproteinase 3 (MMP3), also known as stromelysin-I, is a key-player for carcinogenesis and tumor growth. A 5A/6A promoter polymorphism is associated with differences in MMP3 activity and has been linked to cancer susceptibility in some studies. In the present study we evaluated the role of this polymorphism for breast cancer risk. Experimental Design: A case–control study was performed including 500 patients with histologically confirmed breast cancer and 500 female, age-matched, healthy control subjects from population-based screening studies. The MMP3 5A/6A polymorphism was determined by a 5′-nuclease (TaqMan) assay. Results: Prevalences of 5A/5A, 5A/6A, and 6A/6A genotypes were similar among patients (20.6, 51.8, and 27.6%, respectively) and controls (23.3, 47.3, and 29.4%, P = 0.34). The odds ratio of carriers of a MMP3 5A allele for breast cancer was 1.09 (95% confidence interval, 0.83–1.44). Patients with the 5A/5A genotype had a higher proportion of lymph-node metastases than those with a 5A/6A or 6A/6A genotype (P = 0.010). Conclusions: The MMP3 5A/6A promoter polymorphism does not appear to influence breast cancer susceptibility but may be linked to a higher risk for metastasizing among breast cancer patients.

European Journal of Clinical InvestigationVolume 34, Issue 9 p. 641-642 Improvement of insulin sensitivity in insulin resistant subjects during prolonged treatment with the anti-TNF-α antibody infliximab B. Yazdani-Biuki, Corresponding Author B. Yazdani-Biuki Medical University Graz, Graz, AustriaBabak Yazdani-Biuki Klinische Abteilung für Rheumatologie Medizinische Universitätsklinik Graz Auenbruggerplatz 15 A-8036 Graz, Austria. Tel.: +43 (316) 385 81835; fax: +43 (316) 385 6853; e-mail: babak.yazdanibiuki@unigraz.atSearch for more papers by this authorH. Stelzl, H. Stelzl Medical University Graz, Graz, AustriaSearch for more papers by this authorH. P. Brezinschek, H. P. Brezinschek Medical University Graz, Graz, AustriaSearch for more papers by this authorJ. Hermann, J. Hermann Medical University Graz, Graz, AustriaSearch for more papers by this authorT. Mueller, T. Mueller Medical University Graz, Graz, AustriaSearch for more papers by this authorP. Krippl, P. Krippl Medical University Graz, Graz, AustriaSearch for more papers by this authorW. Graninger, W. Graninger Medical University Graz, Graz, AustriaSearch for more papers by this authorT. C. Wascher, T. C. Wascher Medical University Graz, Graz, AustriaSearch for more papers by this author B. Yazdani-Biuki, Corresponding Author B. Yazdani-Biuki Medical University Graz, Graz, AustriaBabak Yazdani-Biuki Klinische Abteilung für Rheumatologie Medizinische Universitätsklinik Graz Auenbruggerplatz 15 A-8036 Graz, Austria. Tel.: +43 (316) 385 81835; fax: +43 (316) 385 6853; e-mail: babak.yazdanibiuki@unigraz.atSearch for more papers by this authorH. Stelzl, H. Stelzl Medical University Graz, Graz, AustriaSearch for more papers by this authorH. P. Brezinschek, H. P. Brezinschek Medical University Graz, Graz, AustriaSearch for more papers by this authorJ. Hermann, J. Hermann Medical University Graz, Graz, AustriaSearch for more papers by this authorT. Mueller, T. Mueller Medical University Graz, Graz, AustriaSearch for more papers by this authorP. Krippl, P. Krippl Medical University Graz, Graz, AustriaSearch for more papers by this authorW. Graninger, W. Graninger Medical University Graz, Graz, AustriaSearch for more papers by this authorT. C. Wascher, T. C. Wascher Medical University Graz, Graz, AustriaSearch for more papers by this author First published: 17 September 2004 https://doi.org/10.1111/j.1365-2362.2004.01390.xCitations: 99 Division of Rheumatology (B. Yazdani-Biuki, H. P. Brezinschek, J. Hermann, T. Mueller, W. Graninger), Diabetes and Metabolism Clinic (H. Stelzl, T. C. Wascher), and Division of Oncology ( P. Krippl), Department of Internal Medicine, Medical University Graz, Austria. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume34, Issue9September 2004Pages 641-642 RelatedInformation