rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2010-1408rsp-1247Research ArticleСтатьиArticlesПЕРВЫЙ ОПЫТ ПРИМЕНЕНИЯ АДАЛИМУМАБАУ БОЛЬНЫХ АНКИЛОЗИРУЮЩИМ СПОНДИЛИТОМ:КЛИНИЧЕСКОЕ И МРТ-СОПОСТАВЛЕНИЕ РЕЗУЛЬТАТОВ ТЕРАПИИTHE FIRST EXPERIENCE IN USING ADALIMUMAB IN PATIENTS WITH ANKYLOSING SPONDYLITIS: CLINICAL AND MRICOMPARISONS OF THE RESULTS OF THERAPYБочковаА. Г.BochkovaA Gbotchkova@inbox.ru <mailto:botchkova@inbox.ru>RumyantsevaO ARumyantsevaO A-DubininaT VDubininaT V-ЛевшаковаА. В.LevshakovaA V-VakulenkoO YuVakulenkoO Yu-KrasnenkoS OKrasnenkoS O-ЭрдесШ. Ф.ErdesSh F-БочковаА. Г.BochkovaA G-RumyantsevaORumyantsevaO-DubininaT VDubininaT V-ЛевшаковаА. В.LevshakovaA V-VakulenkoO YuVakulenkoO Yu-KrasnenkoS OKrasnenkoS O-ЭрдесШ. Ф.ErdesSh F-201015022010481№1 (2010)6774Copyright © Бочкова А.Г., Rumyantseva O.A., Dubinina T.V., Левшакова А.В., Vakulenko O.Y., Krasnenko S.O., Эрдес Ш.Ф., Бочкова А.Г., Rumyantseva O., Dubinina T.V., Левшакова А.В., Vakulenko O.Y., Krasnenko S.O., Эрдес Ш.Ф., 20102010Бочкова А.Г., Rumyantseva O.A., Dubinina T.V., Левшакова А.В., Vakulenko O.Y., Krasnenko S.O., Эрдес Ш.Ф., Бочкова А.Г., Rumyantseva O., Dubinina T.V., Левшакова А.В., Vakulenko O.Y., Krasnenko S.O., Эрдес Ш.Ф.Bochkova A.G., Rumyantseva O.A., Dubinina T.V., Levshakova A.V., Vakulenko O.Y., Krasnenko S.O., Erdes S.F., Bochkova A.G., Rumyantseva O., Dubinina T.V., Levshakova A.V., Vakulenko O.Y., Krasnenko S.O., Erdes S.F.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1247

Цель. Получение собственного опыта терапии адалимумабом (АДА) у больных анкилозирующим спондилитом (АС), а также уточнение влияния АДА на определяемые при магнитно-резонансной томографии (МРТ) воспалительные изменения (ВИ) в позвоночнике и энтезисах пяток при краткосрочном использовании данного генно-инженерного биологического препарата (ГИБП). Материал и методы. В открытое наблюдение включено 14 пациентов с определенным в соответствии с модифицированными Нью-Йоркскими критериями [4] диагнозом АС, а также 3 пациента с ранним недифференцированным спондилоартритом (нСпА). Для диагностики нСпА использовались критерии ESSG. Для оценки активности, кроме индекса BASDAI, был впервые применен новый международный индекс активности АС - ASDAS, предложенный группой ASAS в 2009 г. Дополнительным критерием активности АС было наличие определяемых при МРТ ВИ в грудном отделе позвоночника, крестцово-подвздошных суставах (КПС) или пяточных костях (у больных с энтезитами пяток). Результаты применения АДА оценивались на 4-й и 14-й неделях исследования. Эффективность терапии оценивалась по критериям ASAS, учитывались 40% улучшение, частичная ремиссия, отдельно оценивалось 50% улучшение по индексу BASDAI. Главным критерием эффективности было число пациентов, достигших частичной ремиссии после 6 инъекций АДА. Результаты. Медиана (Ме) возраста всех пациентов составила 31,6 года [крайние значения (кз): 22-56]; Ме длительности заболеваний - 72 мес [кз: 11-264]. HLA-B27 выявлен у 83% пациентов. Артрит периферических суставов был у 12 больных, энтезиты - у 9. После 2 нед терапии АДА частичная ремиссия была зарегистрирована у 17,8% пациентов, после 12 нед терапии -у 41%; 40% улучшение по критериям ASAS наблюдалось у 58,8% пациентов после 2 нед и более чем у 76,6% - после 6 нед терапии. Индекс активности BASDAI снизился после 2-й инъекции АДА на 50% и более у 47%, после 6-й инъекции - у 86,6% больных с исходно высоким индексом. Индекс активности ASDAS соответствовал низкой активности после 2 нед терапии у 67%, а после 12 нед терапии - у 75% пациентов, имевших исходно высокую активность по этому индексу (>3,0). У 3 пациентов было достигнуто 100% клиническое улучшение состояния энтезисов пяток, подтвержденное данными МРТ-обследования. Ме ВИ в грудном отделе позвоночника через 12 нед терапии хотя и значительно уменьшилась - с 8 (9) до 0 (1), - но различия были недостоверны (p=0,07). Через 12 нед терапии полностью исчезли ВИ в грудном отделе у 1 пациента. Выводы. Улучшение на фоне терапии АДА часто развивалось уже после первых 2 инъекций АДА и сохранялось после 12 нед терапии. АДА быстро и значительно уменьшает выраженность воспаления в структурах позвоночника и энтезисах по данным МРТ.

Objective: To gain experience with adalimumab therapy in patients with ankylosing spondylitis (AS) and to clarify the effect of the drug on MRI-detectable inflammatory changes (IC) in the vertebral column and heel enthesis with the short-term use of this gene engineering biological. Subjects and methods. This open-label observation included 14 patients diagnosed as having AS in accordance with the modified New York criteria [4] and 3 patients with early undifferentiated spondyloarthritis (uSA). The ESSG criteria were used for the diagnosis of uSA. In addition to the BASDAI index, the new international index for disease activity in AS (ASDAS) proposed by the ASAS group in 2009 was first employed to assess the activity of AS. MRI-detectable IC in the thoracic spine, sacroiliac articulation, AND heel bones (in patients with heel enthesitis) was an additional criterion for AS activity. The results of adalimumab use were assessed at weeks 4 and 14 of the study. The efficiency of therapy was evaluated by the ASAS criteria, 40% improvement was taken into account, 50% improvement and partial remission were separately assessed; 50% improvement was assessed by the BASDAI index. The number of patients who had achieved partial remission after 6 adalimumab injections is the major efficiency criterion. Results. The median (Ме) age of all the patients was 31.6 years [range 22-56]; the Ме disease duration was 72 months [range 11-264]. HLA-B27 was detected in 83% of the patients. Peripheral arthritis and enthesitis were present in 12 and 9 patients, respectively. Partial remission was recorded in 17.8 and 41% of patients after 2- and 12-week adalimumab therapy, respectively; 40% ASAS improvement was observed in 58.8 and 76.6% of patients after 2- or more and 6-week therapy, respectively. The BASDAI activity index was decreased by 50% or more in 47 and 86.6% of the patients with the baseline high index after 2 and 6 injections, respectively. The ASDAS activity corresponded to low activity in 67 and 75% of the patients having the baseline high activity in this index (>3.0) after 2- and 12-week therapy, respectively. In 3 patients, 100% clinical improvement in heel enthuses was achieved, as confirmed by MRI data. Although the Ме IC in the thoracic spine substantially diminished from 8 (9) to 0 (1) following 12-week therapy, the differences were insignificant (p=0.07). After 12-week therapy, thoracic IC completely disappeared in one patient. Conclusion. Adalimumab therapy-induced improvement was frequently seen after just the first two injections of adalimumab and preserved after 12-week therapy. Adalimumab rapidly and considerably reduces the magnitude of inflammation in the spinal structures and entheses, as evidenced by МЫ data.

адалимумабанкилозирующий спондилитревматоидный артритэнтезитсакроилиитadalimumabankylosing spondylitisrheumatoid arthritisenthesitissacroiliitisReferences<div><p>Van der Heijde D. et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis. Results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2006;54:2136-46.</p><p>Haibel H., Rudwaleit M., Heldmann F. et al. Efficacy of adalimumab in the treatment of preradiographic axial spondyloarthritis results of a 12-week randomized controlled trial. Arthritis Rheum 2008;58(7):1981-91.</p><p>Sieper J. et al. RHAPSODY. Poster report, EULAR 2008, SAT 0267.</p><p>Van der Linden S., Valkenburg H., Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8.</p><p>Dougados M., van der Linden S., Juhlin R. et al. The European Spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy. Arthr Rheum 1991;34:1218-25.</p><p>Braun J., Pham T., Sieper J. et al. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 2006;62:817-24.</p><p>Garrett S., Jenkinson T., Kennedy L. et al. A new approach to defining disease status in ankylosing spondylitis: the Bath ankylosing spondylitis disease activity index. J Rheumatol 1994;21:2286-91.</p><p>Van der Heijde D., Lie E., Kvien T.K. et al. The ASDAS is a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. Published online 5 Dec 2008.</p><p>Bonel H.M., Boller C.B., Saar B. et al. Short term changes in Magnetic Resonance Imaging and disease activity in response to infliximab. Ann Rheum Dis. Published online 26 Mar 2009.</p><p>Maksimowich W.P., Inman R.D., Salonen D. et al. Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index for Assessment of Spinal Inflammation in Ankylosing Spondylitis. Arthritis Rheum 2005;53:502-9.</p><p>Calin A., Garrett S., Whitelock H. et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994;21(12):2281-5.</p><p>Rudwaleit M., Landewе R., van der Heijde D. et al. SpondyloArthritis international Society (ASAS) Classification Criteria for Axial Spondyloarthritis (Part I): Classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis. Published online 17 Mar 2009.</p><p>Rudwaleit M., Landewе R., van der Heijde D. et al. SpondyloArthritis international Society (ASAS) Classification Criteria for Axial Spondyloarthritis (Part II): Validation and Final Selection. Ann Rheum Dis 2009;68:777-83.</p><p>Hermann K., Haibel H., Althoff C. et al. MRI of the anterior and posterior spinal segment during therapy with adalimumab in active AS. EULAR 2008, Poster SAT 0238.</p><p>Anderson J., Baron G., van der Heijde D. et al. Ankylosing Spondylitis Assessment Group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum 2001;44:1876-86.</p><p>Calin A., Garrett S., Whitelock H. et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath ankylosing spondylitis functional index. J Rheumatol 1994;21:2281-5.</p><p>Rudwaleit M., Listing J., Brandt J. et al. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor-alpha blockers in ankylosing spondylitis. Ann Rheum Dis 2004;63:665-70.</p><p>Sfikakis P., Iliopoulos A., Elezoglou A. et al. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum 2005;52:2513-8.</p><p>Atzeni F., Turiel M., Capsoni F. et al. Autoimmunity and Anti-TNF-alpha Agents. Ann N Y Acad Sci 2005;1051:559-69.</p><p>Haibel H. et al. Adalimumab reduces spinal symptoms in active ankylosing spondylitis: clinical and magnetic resonance imaging results of a fifty-two-week openlabel trial. Ann Rheum Dis 2005;64(Suppl. 3):1036 (abstract).</p><p>Bonel H.M., Boller C., Saar B. Short term changes in Magnetic Resonance Imaging and disease activity in response to infliximab. Ann Rheum Dis. Published online 26 Mar 2009.</p></div><br /><div><p>Van der Heijde D. et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis. Results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2006;54:2136-46.</p><p>Haibel H., Rudwaleit M., Heldmann F. et al. Efficacy of adalimumab in the treatment of preradiographic axial spondyloarthritis results of a 12-week randomized controlled trial. Arthritis Rheum 2008;58(7):1981-91.</p><p>Sieper J. et al. RHAPSODY. Poster report, EULAR 2008, SAT 0267.</p><p>Van der Linden S., Valkenburg H., Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8.</p><p>Dougados M., van der Linden S., Juhlin R. et al. The European Spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy. Arthr Rheum 1991;34:1218-25.</p><p>Braun J., Pham T., Sieper J. et al. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 2006;62:817-24.</p><p>Garrett S., Jenkinson T., Kennedy L. et al. A new approach to defining disease status in ankylosing spondylitis: the Bath ankylosing spondylitis disease activity index. J Rheumatol 1994;21:2286-91.</p><p>Van der Heijde D., Lie E., Kvien T.K. et al. The ASDAS is a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. Published online 5 Dec 2008.</p><p>Bonel H.M., Boller C.B., Saar B. et al. Short term changes in Magnetic Resonance Imaging and disease activity in response to infliximab. Ann Rheum Dis. Published online 26 Mar 2009.</p><p>Maksimowich W.P., Inman R.D., Salonen D. et al. Spondyloarthritis Research Consortium of Canada Magnetic Resonance Imaging Index for Assessment of Spinal Inflammation in Ankylosing Spondylitis. Arthritis Rheum 2005;53:502-9.</p><p>Calin A., Garrett S., Whitelock H. et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994;21(12):2281-5.</p><p>Rudwaleit M., Landewе R., van der Heijde D. et al. SpondyloArthritis international Society (ASAS) Classification Criteria for Axial Spondyloarthritis (Part I): Classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis. Published online 17 Mar 2009.</p><p>Rudwaleit M., Landewе R., van der Heijde D. et al. SpondyloArthritis international Society (ASAS) Classification Criteria for Axial Spondyloarthritis (Part II): Validation and Final Selection. Ann Rheum Dis 2009;68:777-83.</p><p>Hermann K., Haibel H., Althoff C. et al. MRI of the anterior and posterior spinal segment during therapy with adalimumab in active AS. EULAR 2008, Poster SAT 0238.</p><p>Anderson J., Baron G., van der Heijde D. et al. Ankylosing Spondylitis Assessment Group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum 2001;44:1876-86.</p><p>Calin A., Garrett S., Whitelock H. et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath ankylosing spondylitis functional index. J Rheumatol 1994;21:2281-5.</p><p>Rudwaleit M., Listing J., Brandt J. et al. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor-alpha blockers in ankylosing spondylitis. Ann Rheum Dis 2004;63:665-70.</p><p>Sfikakis P., Iliopoulos A., Elezoglou A. et al. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum 2005;52:2513-8.</p><p>Atzeni F., Turiel M., Capsoni F. et al. Autoimmunity and Anti-TNF-alpha Agents. Ann N Y Acad Sci 2005;1051:559-69.</p><p>Haibel H. et al. Adalimumab reduces spinal symptoms in active ankylosing spondylitis: clinical and magnetic resonance imaging results of a fifty-two-week openlabel trial. Ann Rheum Dis 2005;64(Suppl. 3):1036 (abstract).</p><p>Bonel H.M., Boller C., Saar B. Short term changes in Magnetic Resonance Imaging and disease activity in response to infliximab. Ann Rheum Dis. Published online 26 Mar 2009.</p></div><br />

The authors declare that there are no conflicts of interest present.