Efficacy of Anakinra in Active Ankylosing Spondylitis: A Clinical and Magnetic Resonance Imaging Study

Ai Lyn Tan ^1*, Helena Marzo-Ortega ², Philip O'Connor ², Alexander Fraser ², Paul Emery ² and Dennis G McGonagle ³

¹ Leeds General Infirmary and Calderdale Royal Infirmary, UK
² Leeds General Infirmary, UK
³ Leeds General Infirmary and Calderdale Royal Hospital, UK

^* To whom correspondence should be addressed. E-mail: a.l.tan{at}leeds.ac.uk.

Accepted 16 March 2004

Abstract

Objective: To determine the efficacy of anakinra, an interleukin-1 receptor antagonist in active ankylosing spondylitis (AS) and to use magnetic resonance imaging (MRI) to investigate the effect of anakinra therapy on spinal enthesitis/osteitis.

Methods: A 3-month open-label study of anakinra (100mg subcutaneous injection daily) was carried out in 9 patients with active AS who had back pain and an elevated acute phase response, and had failed to response to at least 1 non steroidal anti-inflammatory drug. Clinical assessment included the Bath AS Functional Index (BASFI), Bath AS Disease Activity Index (BASDAI) and AS Quality Of Life (ASQoL) pre and post therapy. Fat suppressed MRI of the spine and sacro- iliac joints were performed using a 1.5T scanner at baseline and at 3 months to determine the effect of therapy on spinal enthesitis/osteitis.

Results: There was a statistically significant improvement in the BASFI (median baseline=5.88, 3- month=3.63, p=0.021), BASDAI (median baseline=5.63, 3- month=3.48, p=0.028), ASQoL (median baseline=12, 3- month=8, p=0.011) and laboratory parameters reflecting inflammation with the C-reactive protein (median baseline=31mg/l, 3-month=17mg/l, p=0.036) and erythrocyte sedimentation rate (median baseline=19mm/hr, 3-month=15mm/hr, p=0.008) also showing significant improvement. Six patients (67%) achieved the Assessments in AS (ASAS) Working Group criteria of 20% improvement. Of the 38 regions of MRI determined enthesitis/osteitis demonstrated at baseline, 61% either improved or regressed completely.

Conclusions: This open label pilot study suggests that anakinra is effective in controlling the clinical manifestations of AS. The clinical response was reflected by an improvement in MRI determined spinal enthesitis/osteitis.

Keywords: Anakinra, Ankylosing spondylitis, Interleukin-1, Magnetic resonance imaging

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Furst, D E, Keystone, E C, Kirkham, B, Fleischmann, R, Mease, P, Breedveld, F C, Smolen, J S, Kalden, J R, Burmester, G R, Braun, J, Emery, P, Winthrop, K, Bresnihan, B, De Benedetti, F, Dorner, T, Gibofsky, A, Schiff, M H, Sieper, J, Singer, N, Van Riel, P L C M, Weinblatt, M E, Weisman, M H (2008). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2008. Ann Rheum Dis 67: iii2-iii25 [Full Text]  
• Sims, A-M, Timms, A E, Bruges-Armas, J, Burgos-Vargas, R, Chou, C-T, Doan, T, Dowling, A, Fialho, R N, Gergely, P, Gladman, D D, Inman, R, Kauppi, M, Kaarela, K, Laiho, K, Maksymowych, W, Pointon, J J, Rahman, P, Reveille, J D, Sorrentino, R, Tuomilehto, J, Vargas-Alarcon, G, Wordsworth, B P, Xu, H, Brown, M A, on behalf of the International Genetics of Ankylos, (2008). Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis. Ann Rheum Dis 67: 1305-1309 [Abstract] [Full Text]  
• Pradeep, D. J., Keat, A., Gaffney, K. (2008). Predicting outcome in ankylosing spondylitis. Rheumatology (Oxford) 47: 942-945 [Full Text]  
• Bennett, A. N., Tan, A. L., Coates, L. C., Emery, P., Marzo-Ortega, H., McGonagle, D. (2008). Sustained response to anakinra in ankylosing spondylitis. Rheumatology (Oxford) 47: 223-224 [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Sieper, J, Emery, P, Keystone, E C, Schiff, M H, Mease, P, van Riel, P L C M, Fleischmann, R, Weisman, M H, Weinblatt, M E (2007). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis 66: iii2-iii22 [Full Text]  
• Bredella, M. A., Steinbach, L. S., Morgan, S., Ward, M., Davis, J. C. (2006). MRI of the sacroiliac joints in patients with moderate to severe ankylosing spondylitis.. Am. J. Roentgenol. 187: 1420-1426 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Emery, P, Keystone, E C, Schiff, M H, van Riel, P L C M, Weinblatt, M E, Weisman, M H (2006). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis 65: iii2-iii15 [Full Text]  
• Zochling, J, van der Heijde, D, Dougados, M, Braun, J (2006). Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Ann Rheum Dis 65: 423-432 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Bijlsma, J W J, Dougados, M, Emery, P, Keystone, E C, Klareskog, L, Mease, P J (2005). Updated consensus statement on biological agents, specifically tumour necrosis factor {alpha} (TNF{alpha}) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases, 2005. Ann Rheum Dis 64: iv2-iv14 [Full Text]  
• Ostensen, M, Forger, F, Nelson, J L, Schuhmacher, A, Hebisch, G, Villiger, P M (2005). Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum. Ann Rheum Dis 64: 839-844 [Abstract] [Full Text]