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      TNF inhibitors appear to inhibit disease progression and improve outcome in Takayasu arteritis; an observational, population-based time trend study

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          Abstract

          Background

          Magnetic resonance imaging (MRI) and computed tomography (CT) angiography have now largely replaced interventional angiography in the diagnoses and follow up of Takayasu arteritis (TAK) but data on the effects of this change of imaging method on diagnostic delay and vascular damage, and detailed data on the effect of different treatment regimens on the accumulation of vascular damage are missing. The aim of this study was to assess time trends in diagnostic delay, therapeutic approaches, arterial lesion accrual, persistent disease activity and remission rates in TAK.

          Methods

          The study cohort included all 78 patients from the 1999 − 2012 population-based South-East Norway TAK cohort and 19 patients from a tertiary referral cohort. TAK was classified by the 1990 American College of Rheumatology criteria and/or the 1995 modified Ishikawa diagnostic criteria. Data were retrieved by review of electronic patient journals and imaging data analyses.

          Results

          Diagnostic delay fell significantly during the study period and the number of lesions at diagnoses fell from three to two. Patients diagnosed from 2000 onwards more often received up-front treatment with disease-modifying antirheumatic drugs (DMARDs) than those diagnosed before 2000 (51% vs 4%; p < 0.01), and they were more often treated with TNF inhibitors during the disease course (44% vs 14%). During the first 2 years after initiation of therapy, 10% (3/32) of TNF-inhibitor-treated patients developed new lesions, compared to 40% (16/40) on DMARD treatment (OR 0.13) and 92% (14/15) on prednisolone monotherapy (OR 0.02). Patients on TNF inhibitors had a higher sustained remission rate than patients on DMARDs (42% vs 20%; p = 0.03). From 2000 onwards, the proportion of patients without new arterial lesions during the first 5 years after diagnosis increased from 29% in the patients diagnosed in 2000–2004, to 39% in 2005–2009 and 59% of patients diagnosed in 2010–2012.

          Conclusion

          Our observational data indicate that more aggressive use of TNF inhibitors and DMARDs improve the outcome in TAK, but damage accrual is a continuous challenge and sustained remission is still relatively rare.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13075-017-1316-y) contains supplementary material, which is available to authorized users.

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          Most cited references25

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          The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis.

          Criteria for the classification of Takayasu arteritis were developed by comparing 63 patients who had this disease with 744 control patients with other forms of vasculitis. Six criteria were selected for the traditional format classification: onset at age less than or equal to 40 years, claudication of an extremity, decreased brachial artery pulse, greater than 10 mm Hg difference in systolic blood pressure between arms, a bruit over the subclavian arteries or the aorta, and arteriographic evidence of narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities. The presence of 3 or more of these 6 criteria demonstrated a sensitivity of 90.5% and a specificity of 97.8%. A classification tree also was constructed with 5 of these 6 criteria, omitting claudication of an extremity. The classification tree demonstrated a sensitivity of 92.1% and a specificity of 97.0%.
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            Takayasu arteritis.

            To evaluate prospectively the clinical features, angiographic findings, and response to treatment of patients with Takayasu arteritis. 60 patients with Takayasu arteritis were studied at the National Institute of Allergy and Infectious Diseases between 1970 and 1990 and were followed for 6 months to 20 years (median follow-up, 5.3 years). Data on clinical features, angiographic and laboratory findings, disease course, and response to therapy were all recorded and stored in a computer-based retrieval system. The Warren Magnuson Clinical Center of the National Institutes of Health. In our series of patients, Takayasu arteritis was more common in Asian persons compared with persons from other racial groups. Females (97%) were most frequently affected. The median age at disease onset was 25 years. Juveniles had a delay in diagnosis that was about four times that of adults. The clinical presentation ranged from asymptomatic to catastrophic with stroke. The most common clinical finding was a bruit. Hypertension was most often associated with renal artery stenosis. Only 33% of all patients had systemic symptoms on presentation. Sixty-eight percent of patients had extensive vascular disease; stenotic lesions were 3.6-fold more common than were aneurysms (98% compared with 27%). The erythrocyte sedimentation rate was not a consistently reliable surrogate marker of disease activity. Surgical bypass biopsy specimens from clinically inactive patients showed histologically active disease in 44% of patients. Although clinically significant palliation usually occurred after angioplasty or bypass of severely stenotic vessels, restenosis was common. Medical therapy was required for 80% of patients, whereas 20% had monophasic self-limiting disease. Immunosuppressive treatment with glucocorticoids alone or in combination with a cytotoxic agent failed to induce remission in one fourth of patients; about half of those who achieved remission later relapsed. In North America, Takayasu arteritis is a rare disease. It is heterogeneous in presentation, progression, and response to therapy. Current laboratory markers of disease activity are insufficiently reliable to guide management. Most patients require repeated and, at times, prolonged courses of therapy. Although mortality was low, substantial morbidity occurred in most patients.
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              Angiographic findings of Takayasu arteritis: new classification.

              Having proposed a new classification on angiographic findings of patients with Takayasu arteritis, we evaluated the angiographic findings of 80 Japanese patients and 102 Indian patients according to this classification. Japanese patients showed a higher frequency of involvement of the ascending aorta, aortic arch and its branches than did the Indians (P < 0.01). On the other hand, the frequency of involvement of the abdominal aorta and/or renal arteries was higher in Indian patients (P < 0.01). Type III cases of the new classification which involves the thoracic descending aorta, abdominal aorta and/or renal arteries were observed in 3% of the Indian patients, but not at all in the Japanese. In conclusion, in Japanese patients, vascular lesions tend to occur primarily in the ascending aorta, aortic arch and/or its branches and extend into the abdominal aorta. On the other hand, in Indian patients, the tendency is primarily in the abdominal aorta including renal arteries and extending into the thoracic aorta.
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                Author and article information

                Contributors
                b.m.gudbrandsson@medisin.uio.no , dr_biggi@hotmail.com
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                18 May 2017
                18 May 2017
                2017
                : 19
                : 99
                Affiliations
                [1 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, , Oslo University Hospital, ; Postboks 4950 Nydalen, 0424 Oslo, Norway
                [2 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Department of Rheumatology, , Oslo University Hospital - Rikshospitalet, ; Oslo, Norway
                Author information
                http://orcid.org/0000-0002-7803-6949
                Article
                1316
                10.1186/s13075-017-1316-y
                5437509
                28521841
                6b7f88ab-a3e6-41e1-856c-3654c3681f5d
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 February 2017
                : 2 May 2017
                Funding
                Funded by: Norske Kvinners Sanitetsforening (NO)
                Award ID: na
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Orthopedics
                takayasu arteritis,diagnostic delay,vascular damage,treatment,biologic,tnf inhibitors,dmards,outcome,remission

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