Ankylosing spondylitis (AS) is a human leukocyte antigen (HLA)-B27-associated chronic inflammatory disease of unknown etiology. There are few effective treatments for ankylosing spondylitis, which causes substantial morbidity. The relationship between AS and enterobacteria, especially Klebsiella pneumoniae, has been reported from several groups in several countries. We performed an open-label trial of moxifloxacin, a fluoroquinolone antibiotic, in patients with ankylosing spondylitis. Treatment with moxifloxacin resulted in significant and sustained improvement. At 12 weeks, patients treated with moxifloxacin had significantly greater improvement in primary outcome measures (P < 0.001). The moxifloxacin group also had significantly greater improvement in many of the secondary outcome measures (P < 0.001). In this twelve-week trial, moxifloxacin was safe, well tolerated, and associated with improvement in the inflammatory symptoms of AS.
* The relationship between ankylosing spondylitis and enterobacteria, especially Klebsiella pneumoniae, has been reported from several groups in several countries.
* Moxifloxacin is effective in patients with ankylosing spondylitis.
* The cause of ankylosing spondylitis may be bacterial.
* Sulfasalazine reduces enterobacteria antibody titrations during treatment for ankylosing spondylitis.
* Randomized controlled trials with a longer treatment period are needed to confirm and establish whether moxifloxacin is effective to treat active ankylosing spondylitis patients.
1. Dougados M, van der Linden S, Juhlin R, et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 1991;34:1218–1227.
2. Feltelius N, Hallgren R. Sulphasalazine in ankylosing spondylitis. Ann Rheum Dis 1986;45:396–399.
3. Davis MJ, Dawes PT, Beswick E, et al. Sulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin. Br J Rheumatol 1989;28:410–413.
4. Ferraz MB, Tugwell P, Goldsmith CH, et al. Meta-analysis of sulfasalazine in ankylosing spondylitis. J Rheumatol 1990;17:1482–1486.
5. Das KM. Sulfasalazine therapy in inflammatory bowel disease. Gastroenterol Clin North Am1989;18:1–20.
6. Tani Y, Sato H, Tanaka N, et al. Antibodies against bacterial lipopolysaccharides in Japanese patients with ankylosing spondylitis. Br J Rheumatol 1997;36:491–493.
7. Maki-Ikola O, Penttinen M, Von Essen R, et al. IgM, IgG and IgA class enterobacterial antibodies in serum and synovial fluid in patients with ankylosing spondylitis and rheumatoid arthritis. Br J Rheumatol 1997;36:1051–1053.
8. Ahmadi K, Wilson C, Tiwana H, et al. Antibodies to Klebsiella pneumoniae lipopolysaccharide in patients with ankylosing spondylitis. Br J Rheumatol 1998;37:1330–1333.
9. Freifeld A, Marchigiani D, Walsh T, et al. A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. N Engl J Med 1999;341:305–311.
10. Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med 1991;324:384–394.
11. Dalhoff A, Shalit I. Immunomodulatory effects of quinolones. Lancet Infect Dis 2003;3:359–371.
12. Shalit I, Kletter Y, Halperin D, et al. Immunomodulatory effects of moxifloxacin in comparison to ciprofloxacin and G-CSF in a murine model of cyclophosphamide-induced leukopenia. Eur J Haematol2001;66:287–296.
13. Weiss T, Shalit I, Blau H, et al. Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines. Antimicrob Agents Chemother 2004;48:1974– 1982.
14. Araujo FG, Slifer TL, Remington JS. Effect of moxifloxacin on secretion of cytokines by human monocytes stimulated with lipopolysaccharide. Clin Microbiol Infect 2002;8:26–30.
15. 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;27:361–368.
16. Garrett S, Jenkinson T, Kennedy LG, et al. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21:2286–2291.
17. Callin 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;21:2281–2285.
18. Toussirot E, Wendling D. Current guidelines for the drug treatment of ankylosing spondylitis. Drugs 1998;56:225–240.
19. Steven MM, Morrison M, Sturrock RD. Penicillamine in ankylosing spondylitis: a double blind placebo controlled trial. J Rheumatol 1985;12:735–737.
20. Gratacos J, Collado A, Filella X, et al. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol 1994;33:927–931.
21. Grom AA, Murray KJ, Luyrink L, et al. Patterns of expression of tumor necrosis factor alpha, tumor necrosis factor beta, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy. Arthritis Rheum 1996;39:1703–1710.
22. Braun J, Bollow M, Neure L, et al. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 1995;38:499–505.
23. Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 2002;346:1349–1356.
24. Reato G, Cuffini AM, Tullio V, et al. Immunomodulating effect of antimicrobial agents on cytokine production by human polymorphonuclear neutrophils. Int J Antimicrob Agents 2004;23:150–154.
25. Seymour GJ, Gemmell E. Cytokines in periodontal disease: where to from here? Acta Odontol Scand 2001;59:167–173.
26. Yoshimura A, Hara Y, Kaneko T, et al. Secretion of IL-1 beta, TNF-alpha, IL-8 and IL-1ra by human polymorphonuclear leukocytes in response to lipopolysaccharides from periodontopathic bacteria. J Periodontal Res 1997;32:279–286.
27. Huet S, Nixon DF, Rothbard JB, et al. Structural homologies between two HLA B27-restricted peptides suggest residues important for interaction with HLA B27. Int Immunol 1990;2:311–316.
28. Ren EC, Koh WH, Sim D, et al. Possible protective role of HLA-B*2706 for ankylosing spondylitis.Tissue Antigens 1997;49:67–69.
29. Sesma L, Montserrat V, Lamas JR, et al. The peptide repertoires of HLA-B27 subtypes differentially associated to spondyloarthropathy (B*2704 and B*2706) differ by specific changes at three anchor positions. J Biol Chem 2002;277:16744–16749.