Evaluation of the effects of tumor necrosis factor-а inhibitors versus nonsteroidal anti-inflammatory drugs on spinal inflammatory changes from magnetic resonance imaging data in patients with ankylosing spondylitis

Objective: to evaluate the time course of inflammatory changes (ICs) in the spinal column and sacroiliac articulations (SIA) from magnetic resonance imaging (MRI) data in patients with ankylosing spondylitis (AS) during treatment with tumor necrosis factor-α (TNF-а) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs), which were first used. Subjects and methods. MRI of the most painful part of the spine and SIA was performed in 58 patients with AS at baseline and 12 weeks later. MRI T2 STIR and T1 (SIGNA EXCITE, General Electrics; 0.35 T, matrix 288x192) regimens were used. Bone marrow edema was regarded as active inflammation. Active ICs in the most painful part of the spine were assessed by the AS spinal MRI activity (ASspiMRI-a) score and those in SIA by the Leeds scoring system. MRI was interpreted independently by two specialists; one of them did not know about the number of a visit and performed therapy. The patients were divided into two groups: 1) those who first used TNF-а inhibitors and 2) those who were first given NSAIDs. Both groups were matched for demographic indicators. Results. In both groups, the mean pain level in the spinal part under study decreased significantly in both groups: from 5.7±1.7 to 2.3±1.8 in the TNF-а inhibitor group (p = 0.000006) and from 4.8±2.3 to 2.6±2.3 in the NSAID group (р = 0.00001). After 12 weeks of treatment, the patients receiving TNF-а inhibitors (n = 28) showed a considerable reduction in the MRI signs of spinal ICs from 4.8±2.3 to 1.6±1.6 (p = 0.00001); moreover, this trend was more pronounced in patients (n = 17) with more baseline IC foci (≥ 5) than in those (n = 11) with fewer baseline IC foci (< 5) (the mean а was 4.3±1.5 and 1.6±1.4, respectively; р = 0.0003). In the patients taking NSAIDs (n = 30), the decrease in the number of spinal MRI ICs (from 2.8±2.5 to 2.3±2.1) was insignificant (p = 0.17). After 12 weeks, regression of active sacroiliitis was noted in 28 patients from the TNF-а inhibitor group with lower Leeds scores from 2.1±2.0 to 0 (p = 0.01). At baseline, 28.5% of the patients had MRI signs of active sacroiliitis, which were not found in any case at 12 weeks. At this time, the reduction in active sacroiliitis was also observed in the NSAID group patients (n = 30), but it was insignificant; the Leeds scores decreased from 2.6±2.5 to 2.1±2.0 (р = 0.083). At baseline and 12 weeks, the MRI signs of active sacroiliitis were present in 73.3 and 60% of the patients, respectively. During treatment with TNF-а inhibitors, the mean reduction in MRI IC scores during the follow-up was more marked than that in the use of NSAIDs (p = 0.003 for the spinal column and p = 0.013 for SIA). Conclusion. Pain intensity in the examined spinal part was significantly reduced in both the use of both TNF-а inhibitors and NSAIDs. MRI ICs significantly decreased when treated with TNF-а inhibitors rather than NSAIDs. With the greater magnitude of baseline MRI ICs, their drop was more significant during treatment with TNF-α inhibitors.

inflammatory changes, spondyloarthritis, active sacroiliitis, magnetic resonance imaging, tumor necrosis factor-α (TNF-α) inhibitors, nonsteroidal anti-inflammatory drugs

1. <div><p>Sieper J., Rudwaleit M., Baraliakos X. et al. The Assesment of Spondyloarthritis international Society (ASAS) Handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009;68(Suppl. II):ii1-ii44.</p><p>Braun J., Bollow M., Sieper J. Radiology and pathology of the spondyloarthropathies. Rheum Dis Clin North Am 1998;24:697-735.</p><p>Левшакова А.И., Бочкова А.Г., Бунчук Н.В., Кротенкова М.В. Магнитно-резонансная томография в диагностике воспалительных изменений позвоночника у больных анкилозирующим спондилитом. Мед визуализация 2010;6:96-105.</p><p>Braun J., Baraliakos X., van den Berg R. et al. 2010 update of the ASAS/EULAR recommendations for the management of AS. Ann Rheum Dis 2011;70:896-904.</p><p>Бочкова А.Г. Рекомендации EULAR: ведение больных анкилозирующим спондилитом. Совр ревматол 2009;4:5-10.</p><p>Puhakka K.B., Jurik A.G., Egund N. et al. Imaging of sacroiliitis in early seronegative spondylarthropathy. Assessment of abnormalities by MRI in comparison with radiography and CT. Acta Radiol 2003;44:218-29.</p><p>Braun J., Baraliakos X., Golder W. et al. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system. Arthr Rheum 2003;48:1126-36.</p><p>Левшакова А.В., Бочкова А.Г., Бунчук Н.В. МРТ крестцовоподвздошных суставов у больных анкилозирующим спондилитом. Мед визуализация 2008;2:97-103.</p><p>Бочкова А.Г., Левшакова А.В., Румянцева О.А, Бунчук Н.В. Воспалительные изменения позвоночника у больных анкилозирующим спондилитом по данным магнитно-резонансной томографии. Науч-практич ревматол 2008;5:17-25.</p><p>Baraliakos X., Landewer R., Hermann K.-G. et al. Inflammation in ankylosing spondylitis: a systematic description of the extent and frequency of acute spinal changes using magnetic resonance imaging. Ann Rheum Dis 2005;64:730-4.</p><p>Van der Heijde D.M., Landewe R.B., Hermann K.G. et al. Application of the OMERACT filter to scoring methods for magnetic resonance imaging of the sacroiliac joints and the spine: recommendations for a research agenda at OMERACT 7. J Rheumatol 2005;32:2042-7.</p><p>Van der Heijde D., Landewe R., Hermann K.G. et al. Is there a preferred method for scoring activity of the spine by magnetic resonance imaging in ankylosing spondylitis? Ann Rheum Dis 2007;34(4):871-4.</p><p>Левшакова А.В., Бочкова А.Г., Бунчук Н.В. Магнитно-резонансная томография позвоночника в оценке эффективности терапии анкилозирующего спондилита. Луч диагн тер 2010;2:61-3.</p><p>Rudwaleit M., Baraliakos X., Listing J. et al. Magnetic resonance imaging of the spine and the sacroiliac joints in ankylosing spondylitis and undifferentiated spondyloarthritis during treatment with etanercept. Ann Rheum Dis 2005;64:1305-10</p><p>Braun J., Landewe R., Hermann K.G. et al. ASSERT Study Group. Major reduction in spinal inflammation in patients with AS after treatment with infliximab: results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study. Arthr Rheum 2006;54:1646-52.</p><p>Lambert R.G., Salonen D., Inman R.D. et al. Adalimumab significantly reduces both spinal and SI joint inflammation in patients with AS: a multicenter, randomized, double-blind, placebo-controlled study. Ann Rheum 2007;56:4005-14.</p><p>Boersma J.W. Retardation of ossification of the lumbar vertebral column in ankylosing spondylitis by means of phenylbutazon. Scand J Rheumatol 1976;5:60-4.</p><p>Wanders A., van der Heijde D., Landewe R. et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: A randomized clinical trial. Arthr Rheum 2005;52(6):1756-65.</p><p>Poddubnyy D., Haibel H., Listing J. et al. Influence of NSAIDs intake on the radiographic spinal progression over two years in patients with early axial spondyloarthritis. Ann Rheum Dis 2011;70(Suppl. 3):128.</p><p>Garrett S., Jenkinson T., Kennedy L.G. et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21(12):2286-91.</p><p>Dougados М., Paternotte S., Braun J. et al. ASAS recommendations for collecting, analysing and reporting NSAID intake in clinical trials/epidemiological studies in axial spondyloarthritis. Ann Rheum Dis 2011;70:249-51.</p><p>Zochling J., Van der Heijde D., Burgos-Vargas R. et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006;54:442-52.</p><p>Rudwaleit M., Jurik A.G., Hermann K.-G.A. et al. Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI group. Ann Rheum Dis. 2009;68:1520-7.</p><p>Петри А., Сэбин К. Наглядная статистика в медицине: Пер. с англ. М.: ГЭОТАР-мед., 2003.</p><p>Marzo-Ortega H., McGonagle D., O’Connor P., Emery P. Efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthropathy: a clinical and magnetic resonance imaging study. Arthr Rheum 2001;44:2112-7.</p><p>Baraliakos X., Brandt J., Listing J. et al. Outcome of patients with active AS after two years of therapy with etanercept: clinical and MRI data. Arthr Rheum 2005;53:856-63.</p><p>Rudwaleit M., Schwarzlose S., Hilgert E.S. et al. MRI in predicting a major clinical response to anti-tumour necrosis factor treatment in ankylosing spondylitis. Ann Rheum Dis 2008;67:1276-81.</p><p>Crowther S.M., Lambert R.G.W., Dhillon S.S., Maksymowych W.P. Systematic assessment of inflammation by magnetic resonance imaging in the posterior elements of the spine in ankylosing spondylitis. Arthr Care Res (Hoboken) 2010;62(1):4-10.</p><p>Song I.H., Hermann K.G., Haibel H. et al. Relationship between active inflammatory lesions in the spine and sacroiliac joints and new development of chronic lesions on whole-body MRI in early axial spondyloarthritis: results of the ESTHER trial at week 48. Ann Rheum Dis 2011;70:1257-63.</p><p>Chiowchanwisawakit P., Lambert R.G., Conner-Spady B., Maksymowych W.P. Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis. Arthr Rheum 2011;63(8):2215-25.</p><p>Van der Heijde D., Landewe R., Einstein S. et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthr Rheum 2008;58(5):1324-31.</p><p>Jarrett S.J., Sivera F., Cawkwell L.S. et al. MRI and clinical findings in patients with ankylosing spondylitis eligible for anti-tumour necrosis factor therapy after a short course of etoricoxib. Ann Rheum Dis 2009;68:1466-9.</p><p>Haibel H., Song I.H., Rudwaleit M. et al. Multicenter open-laibel study with infliximab in active ankylosing spondylitis over 28 weeks in daily practice. Clin Exp Rheumatol 2008;26(2):247-52.</p><p>Brandt J., Khariouzov A., Listing J. et al. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthr Rheum 2003;48:1667-75.</p></div><br />