Efficacy and safety of intravenous methylprednisolone in the treatment of patients with active ankylosing spondylitis: Results of a 12-week, prospective, open-label, pilot (METALL) study


Cite item

Full Text

Abstract

Aim. To evaluate the efficacy and safety of intravenous methylprednisolone (MP) 500 mg in patients with active ankylosing spondylitis (AS) and the inefficiency, intolerability of or contraindications to treatment with 2 or more non-steroidal anti-inflammatory drugs (NSAIDs). Subjects and methods. The investigation enrolled 20 patients (age, 35.35±8.19 years) with a 10.2±9.2year history of AS who met the modified New York criteria) and had its activity defined as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 scores and an inadequate response to and intolerance of ≥2 NSAIDs; there were 13 (65%) men. MP was given in a single intravenous dose of 500 mg. The main efficiency criterion (primary study endpoint) was considered to be the number of patients who had achieved an ASAS20 response at week 2. Additional rating criteria (secondary endpoints) (improved BASDAI/ASDAS; decreased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels; the number of patients achieving ASAS20/40/5/6 responses and ASAS partial remission, and improved ASDAS) were calculated 2, 4, and 12 weeks after MP administration. Safety was monitored estimating the frequency of adverse events (AEs) and controlling vital functions and laboratory indicators. Results. Nine (45%) patients achieved an ASAS40 response at week 2. ASDAS was 3.48 at baseline and 2.21 at week 2 (p<0.0001). ASDAS clinical improvement was established in 11 (55%) patients at week 2. There were decreases in BASDAI from 6.6 to 3.7 at week 2, to 3.5 at week 4, and to 3.2 at week 12 (p<0.001). CRP levels declined from 6.1 to 3.15 mg/l at week 2 (p<0.05), to 2.85 mg/l at week 4 (p<0.001), and to 4.6 mg/l at week 12 (p<0.05). ESR was 6.5 mm/h at baseline, 5.5 mm/h at week 2 (p<0.05), 6.0 mm/h at week 4, and 7.0 mm/h at week 12 (p > 0.05). A total of 13 AEs were recorded and no serious AEs were noted. Conclusion. Pulse therapy with MP 500 mg is safe and effective in the short-term treatment of patients with active AS who have achieved no benefits of NSAIDs.

References

  1. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007; 369(9570):1379-1390.
  2. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, Dagfinrud H, Dijkmans B, Dougados M, Emery P, Geher P, Hammoudeh M, Inman RD, Jongkees M, Khan MA, Kiltz U, Kvien T, Leirisalo-Repo M, Maksymowych WP, Olivieri I, Pavelka K, Sieper J, Stanislawska-Biernat E, Wendling D, Ozgocmen S, van Drogen C, van Royen B, van der Heijde D. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011;70(6):896-904.
  3. Peeters H, Vander Cruyssen B, Laukens D, Coucke P, Marichal D, Van Den Berghe M, Cuvelier C, Remaut E, Mielants H, De Keyser F, Vos MD. Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn’s disease. Ann Rheum Dis. 2004;63(9):1131-1134.
  4. Braun J, Deodhar A, Dijkmans B, Geusens P, Sieper J, Williamson P, Xu W, Visvanathan S, Baker D, Goldstein N, van der Heijde D; Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study Group. Efficacy and safety of infliximab in patients with ankylosing spondylitis over a two-year period. Arthritis Rheum. 2008;59(9):1270-1278.
  5. Davis JC Jr, van der Heijde DM, Braun J, Dougados M, Clegg DO, Kivitz AJ, Fleischmann RM, Inman RD, Ni L, Lin SL, Tsuji WH. Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis. Ann Rheum Dis. 2008;67(3):346-352.
  6. van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, Kupper H, Dijkmans BA, Mease PJ, Davis JC Jr; ATLAS Study Group. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis. 2008;17:1272-1276.
  7. Haibel H, Fendler C, Listind J, Callhoff J, Braun J, Sieper J. Efficacy of oral prednisolone in active ankylosing spondylitis: results of double-blind, randomised placebo-controlled short-term trial. Ann Rheum Dis. 2014;73:243-246.
  8. Румянцева О.А., Бочкова А.Г., Логинова Е.Ю., Киселева Н.М., Пушкова О.В., Бунчук Н.В. Внутривенное применение высоких доз глюкокортикоидов у больных анкилозирующим спондилитом. Терапевтический архив. 2006;78(12):71-74.
  9. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361-368.
  10. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21(12):2286-2291.
  11. Hoes JN, Jacobs JW, Boers M, Boumpas D, Buttgereit F, Caeyers N, Boumpas D, Buttgereit F, Caeyers N, Choy EH, Cutolo M, Da Silva JA, Esselens G, Guillevin L, Hafstrom I, Kirwan JR, Rovensky J, Russell A, Saag KG, Svensson B, Westhovens R, Zeidler H, Bijlsma JW. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2007;66(12):1560-1567.
  12. Buttgereit F, da Silva JA, Boers M, Burmester GR, Cutolo M, Jacobs J, Kirwan J, Köhler L, Van Riel P, Vischer T, Bijlsma JW. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis. 2002;61(8):718-722.
  13. Lipworth BJ. Therapeutic implications of non-genomic glucocorticoid activity. Lancet. 2000;356(9224): 87-89.
  14. Richter MB, Woo P, Panayi GS, Trull A, Unger A, Shepherd P. The effects of intravenous pulse methylprednisolone on immunological and inflammatory processes in ankylosing spondylitis. Clin Exp Immunol. 1983;53(1):51-59.
  15. Peters ND, Ejstrup L. Intravenous methylprednisolone pulse therapy in ankylosing spondylitis. Scand J Rheumatol. 1992;21(3):134-138.
  16. Mintz G, Enriquez RD, Mercado U, Robles EJ, Jimenez FJ, Gutierrez G. Intravenous methylprednisolone pulse therapy in severe ankylosing spondylitis. Arthritis Rheum. 1981;24(5):734-736.
  17. Brandt J, Listing J, Sieper J, Rudwaleit M, van der Heijde D, Braun J. Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis. Ann Rheum Dis. 2004;63(11):1438-1444.
  18. Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001;44(8):1876-1886.
  19. van der Heijde D, Lie E, Kvien TK, Sieper J, Van den Bosch F, Listing J, Braun J, Landewé R; Assessment of SpondyloArthritis international Society (ASAS). ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(12):1811-1818.
  20. Machado P, Landewe R, Lie E, Kvien TK, Braun J, Baker D, Kvien TK, Braun J, Baker D, van der Heijde D; Assessment of SpondyloArthritis international Society. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis. 2010;70(1):47-53.
  21. Calin A, Garrett S, Whitelock H, Kennedy LG, O’Hea J, Mallorie P, Jenkinson T. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol. 1994;21(12):2281-2285.
  22. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landew? R, van ver Tempel H, Mielants H, Dougados M, van der Heijde D. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 2003;62(2):127-132.
  23. Реброва О.Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA. М.: Медиа-Сфера; 2002.
  24. Durez P, Malghem J, Nzeusseu Toukap A, Westhovens R, Depresseux G, Lauwerys BR, Westhovens R, Luyten FP, Corluy L, Houssiau FA, Verschueren P. Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone. Arthritis Rheum. 2007; 56(12):3919-3927.
  25. Fendler C, Baraliakos X, Braun J. Glucocrticoid treatment in spondyloarthritis. Clin Exp Rheumatol. 2011;29(5 Suppl 8):S139-S142.
  26. Бочкова А.Г. Роль глюкокортикоидов в лечении спондилоартритов. Современная ревматология. 2011;1:76-78.
  27. Keun Lee, Eun Young Lee, You-Sook Cho, Moon KA, Yoo B, Moon HB. Increased Expression of Glucocorticoid Receptor? Messenger RNA in Patients with Ankylosing Spondylitis. Korean J Int Med. 2005;20:146-151.
  28. Akkoc N, van der Linden S, Khan MA. Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy. Best Pract Res Clin Rheumatol. 2006;20(3):539-557.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2015 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

 © 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies