EFFICIENCY OF ANTI-INFLAMMATORY THERAPY IN PATIENTS WITH ANKYLOSING SPONDYLITIS ACCORDING TO THE RESULTS OF A PROSPECTIVE FOLLOW-UP STUDY

In accordance  with the Ankylosing Spondylitis Assessments (ASAS) International Working Group guidelines, tumor necrosis factor-α  inhibitors are recommended in patients with ankylosing spondylitis (AS) refractory to at least two nonsteroidal  anti-inflammatory drugs (NSAIDs)  and in those with the peripheral form of the disease. Previous investigations suggest that when long used, infliximab (INF) shows a steady-state efficacy in the vast majority of patients with active AS. Works evaluating the efficiency of combined therapy using NSAIDs and INF are scarce. Objective: to evaluate the efficiency of therapy with NSAIDs and INF in patients with AS from the results of a prospective study.

Subjects and methods. A total of 72 men with a valid diagnosis of AS were followed up. All the patients were allocated to two groups according to the option of basic therapy: 1) 29 patients received combined therapy with INF and NSAIDs; 2) 43 had NSAID monotherapy. Clinical, laboratory, and instrumental  examinations were performed every 12 months. Results and discussion. At 12 months of INF therapy, there were significant reductions in the values of BASDAI, BASFI, back pain, fatigue, and patient-rated global activity assessment. High BASDAI values remained in only 10 patients.

At 24-month follow-up, the above measures did not significantly change as compared to the results obtained at 12 months and remained stable at 36 months. At 12 months of NSAID therapy, there were significant reductions in the values of BASDAI, back pain, fatigue, and patient-rated global activity assessment (p < 0.05). The reduction in BASFI values was insignificant. At 24 months of treatment all the measures versus those obtained after 12 months did not significantly change, except pain in the examined region of the spine, which became significantly severer than that at the 12-month follow-up. These results were also preserved at 36 months. There were more patients achieving 20% and 40% improvements and remission according to the ASAS criteria, and those with a 50% BASDAI improvement after 36 months of INF + NSAID therapy versus NSAID monotherapy (p < 0.05).

Conclusion. The highest clinical effect of INF + NSAID therapy was observed within the first year and the measures in question remained stable at the 36-month follow-up after both treatments. 

1. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369(9570):1379-90. doi: 10.1016/S0140-6736(07)60635-7

2. Braun J, van den Berg R, Baraliakos X, et al. Update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011;70(6):896-904. doi: 10.1136/ard.2011.151027

3. Агабабова ЭР. Современные направления исследований при спондилоартропатиях: Актовая речь. В кн.: Первый Всероссийский конгресс ревматологов. Саратов; 2003. С. 31 [Agababova ER. Current areas of research at spondyloarthropathies: acts of speech. In: Pervyi Vserossiiskii kongress revmatologov [First All-Russian Congress of Rheumatology]. Saratov; 2003. P. 31].

4. Бадокин ВВ. Симптом-модифицирующая терапия анкилозирующего спондилоартрита. Русский медицинский журнал. 2004;12(6):433-40 [Badokin VV. Symptom-modifying treatment of ankylosing spondylitis. Russkii Meditsinskii Zhurnal. 2004;12(6):433-40 (In Russ.)].

5. Волнухин ЕВ, Галушко ЕА, Бочкова АГ и др. Клиническое многообразие анкилозирующего спондилита в реальной практике врача-ревматолога в России (часть 1). Научнопрактическая ревматология. 2012;50(2):44-9 [Volnukhin EV, Galushko EA, Bochkova AG, et al. Clinical diversity of ankylosing spondylitis in the real practice of a rheumatologist in Russia (Part 1). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2012;50(2):44-9 (In Russ.)]. doi: 10.14412/1995-4484-2012-1272.

6. Фоломеева ОМ, Галушко ЕА, Эрдес ШФ. Распространенность ревматических заболеваний в популяциях взрослого населения России и CША. Научно-практическая ревматология. 2008;46(4):4-13 [Folomeeva OM, Galushko EA, Erdes ShF. Prevalence of rheumatic diseases in adult populations of Russian Federation and USA. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2008;46(4):4-13 (In Russ.)]. doi: 10.14412/1995-4484-2008-529

7. Юшина СА. Особенности метаболизма костной ткани у больных анкилозирующим спондилоартритом: Aвтореф. дис. … канд. мед. наук. Оренбург; 2012. 27 c. [Yushina SA. Osobennosti metabolizma kostnoi tkani u bol'nykh ankiloziruyushchim spondiloartritom: Avtoref. dis. … kand. med. nauk [Features of bone metabolism in patients with ankylosing spondylitis: Abstract Dis. ... Cand. Med. Sci.]. Orenburg; 2012. 27 p.].

8. Braun J, Bollow M, Sieper J. Radiology and pathology of the spondyloarthropathies. Rheum Dis Clin North Am. 1998;24(4):697-735. doi: 10.1016/S0889-857X(05)70038-7

9. Braun J, Davis J, Dougados M, et al. First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2006;65(3):316-20. doi: 10.1136/ard.2005.040758

10. Мясоутова ЛИ, Лапшина СА, Салихов ИГ и др. Изменение минеральной плотности костной ткани у больных анкилозирующим спондилоартритом. Остеопороз и остеопатии. 2011;(3):14-8 [Myasoutova LI, Lapshina SA, Salikhov IG, et al. Measurement of bone mineral density in patients with ankylosing spondylitis. Osteoporoz i Osteopatii. 2011;(3):14-8 (In Russ.)].

11. Chen J, Lui C. Sulfasalasin for ankylosing spondylitis. Cochrane Database Syst Rev. 2005;(2):CD004800.

12. Gran J, Skomsvoll JF. The outcome of ankylosing spondylitis: a study of 100 patients. Br J Rheumatol. 1997;36(7):766-71. doi: 10.1093/rheumatology/36.7.766

13. Haibel H, Brandt HC, Song IH, et al. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16 weeks open label trial. Ann Rheum Dis. 2007;66(3):419-21. doi: 10.1136/ard.2006.054098

14. Румянцева ОА, Бочкова АГ, Кузикянц КХ и др. Опыт длительной терапии инфликсимабом у больных анкилозирующим спондилитом. Научно-практическая ревматология. 2010;48(6):16-22 [Rumyantseva OA, Bochkova AG, Kuzikyants KK, et al. Experience with long-term infliximab therapy in patients with ankylosing spondylitis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2010;48(6):16-22. (In Russ.)]. doi: 10.14412/1995-4484-2010-818

15. Бадокин ВВ. Медикаментозная терапия анкилозирующего спондилоартрита. Русский медицинский журнал. 2004;12(20):1128-36 [Badokin VV. Drug therapy of ankylosing spondylitis. Russkii Meditsinskii Zhurnal. 2004;12(20):1128-36 (In Russ.)].

16. Румянцева ОА, Бочкова АГ, Логинова ЕЮ и др. Исследование эффективности, безопасности и переносимости инфликсимаба у больных анкилозирующим спондилитом (предварительные результаты). Научно-практическая ревматология. 2006;(4):11-20 [Rumyantseva OA, Bochkova AG, Loginova EYu, et al. The study of efficacy, safety and tolerability of infliximab in patients with ankylosing spondylitis (preliminary results). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2006;(4):11-20 (In Russ.)].

17. Devogelaer JP, Maldague В, Malghem J, et al. Appendicular and vertebral bone mass in ankylosing spondylitis. A comparison of plane radiographs with singleand dual-photon absorptiometry and with quantitative computed tomography. Arthritis Rheum. 1992;35(9):1062-7. doi: 10.1002/art.1780350911

18. Will R, Palmer R, Bhalla AK, et al. Вone loss as well as bone formation is a feature of progressive ankylosing spondylitis. Br J Rheumatol. 1990;29(6):498-9. doi: 10.1093/rheumatology/29.6.498-b

19. Borcan M, Matei D, Popescu R. Management of osteoporosis in ankylosing spondylitis. Osteoporosis Int. 2011;22(1):309-10.

20. Van Denderen JC, van der Paardt M, Nurmohamed MT, et al. Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis. Ann Rheum Dis. 2005;64(12):1761-4. doi: 10.1136/ard.2005.036491

21. Van den Bosch F, Devink M, Kruithof E, et al. 5-year safety and efficacy follow-up in 107 spondyloarthropathy patients with continued lond-term infliximab treatment. Ann Rheum Dis. 2005;64(3):1079.

22. Беневоленская ЛИ, Лесняк ОМ, редакторы. Остеопороз. Диагностика, профилактика и лечение: Клинические рекомендации. Москва: ГЭОТАР-Медиа; 2011. С. 14 [Benevolenskaya LI, Lesnyak OM, editors. Osteoporoz. Diagnostika, profilaktika i lechenie: Klinicheskie rekomendatsii [Osteoporosis. Diagnosis, Prevention and Treatment: Clinical Recommendations]. Moscow: GEOTAR-Media; 2011. P. 14].

23. Tan KB, Harrop J, Reddy M, et al. Characterization of a novel TNF-like ligand and recently described TNF ligand and receptor superfamily genes and their constutive and inducible expression in hematopoietic and nonhematopoietic cells. Gene. 1997;204(1-2):35-46. doi: 10.1016/S0378-1119(97)00509-X

24. Инструкция по применению инфликсимаба компании Centocor Inc. от 17 мая 2006 г. [Электронный ресурс]. Centocor Inc. – URL: http://www.fda.gov (дата обращения 05.03.2013) [Instructions on the use of infliximab company Centocor Inc. dated May 17, 2006. [electronic resource]. Centocor Inc. – URL: http://www.fda.gov (reference date of 05.03.2013)].

25. Braun J, Brandt J, Listing J, et al. Two year maintenance of efficacy and safety of infliximab in the treatment of ankylosing spondylitis. Ann Rheum Dis. 2005;64(2):229-34. doi: 10.1136/ard.2004.025130

26. Van der Linden, Cats A, Valkenburg H. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum.1984;27(4):361-8. doi: 10.1002/art.1780270401

27. Gorman J, Sack K, Davis J. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor a. N Engl J Med. 2002;346(18):1349-56. doi: 10.1056/NEJMoa012664.