J Korean Med Sci.  2013 Aug;28(8):1134-1138. 10.3346/jkms.2013.28.8.1134.

Tofacitinib Prevents Radiographic Progression in Rheumatoid Arthritis

• Kim JW
• Choi IA
• Lee EY
• Song YW
• Lee EB

• KMID: 1793016
• DOI: http://doi.org/10.3346/jkms.2013.28.8.1134

Abstract

Tofacitinib, a novel Janus kinase inhibitor, may prevent structural damage in rheumatoid arthritis (RA). In this cohort study, we compared radiographic progression of hand joints between 21 RA patients who took tofacitinb for 18 months in a phase IIb and its extension study and 42 patients who took conventional disease modifying antirheumatic drugs (DMARDs), using simple erosion narrowing score. For tofacitinib group, changes before and after the treatment were also compared. The changes of erosion and sum scores were significantly less in tofacitinib than DMARDs group (for erosion, -0.60 +/- 1.83 vs 0.51 +/- 1.77, P = 0.038; for sum, -0.50 +/- 1.72 vs 1.57 +/- 4.13, P = 0.012). Joint space narrowing score (JSN) was also less in tofacitinib group (0.095 +/- 0.58 vs 1.06 +/- 2.60, P = 0.055). In tofacitinib group, yearly rates of both erosion and JSN were significantly decreased after administration of tofacitinib (For erosion, 0.62 +/- 0.93 to -0.14 +/- 0.48, P = 0.009; for JSN, 0.47 +/- 0.64 to 0.03 +/- 0.40, P = 0.032), as was change of sum score (1.09 +/- 1.27 to -0.10 +/- 0.63, P < 0.001). In conclusion, tofacitinib may prevent structural damage caused by RA.

Keyword

Arthritis, Rheumatoid; Radiographic Progression; Tofacitinib

MeSH Terms

Adult
Aged
Antirheumatic Agents/therapeutic use
Arthritis, Rheumatoid/*drug therapy/prevention & control/radiography
Cohort Studies
Disease Progression
Female
Humans
Male
Middle Aged
Piperidines/*therapeutic use
Protein Kinase Inhibitors/*therapeutic use
Pyrimidines/*therapeutic use
Pyrroles/*therapeutic use
Severity of Illness Index
Treatment Outcome
Antirheumatic Agents
Piperidines
Protein Kinase Inhibitors
Pyrimidines
Pyrroles

Reference

1. McInnes IB, O'Dell JR. State-of-the-art: rheumatoid arthritis. Ann Rheum Dis. 2010; 69:1898–1906.

2. Karmakar S, Kay J, Gravallese EM. Bone damage in rheumatoid arthritis: mechanistic insights and approaches to prevention. Rheum Dis Clin North Am. 2010; 36:385–404.

3. Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999; 402:304–309.

4. Van der Heijde D, Landewé R, van Vollenhoven R, Fatenejad S, Klareskog L. Level of radiographic damage and radiographic progression are determinants of physical function: a longitudinal analysis of the TEMPO trial. Ann Rheum Dis. 2008; 67:1267–1270.

5. Van der Heijde DM. Radiographic imaging: the 'gold standard' for assessment of disease progression in rheumatoid arthritis. Rheumatology (Oxford). 2000; 39:9–16.

6. Van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol. 1999; 26:743–745.

7. Ideguchi H, Ohno S, Hattori H, Senuma A, Ishigatsubo Y. Bone erosions in rheumatoid arthritis can be repaired through reduction in disease activity with conventional disease-modifying antirheumatic drugs. Arthritis Res Ther. 2006; 8:R76.

8. Abu-Shakra M, Toker R, Flusser D, Flusser G, Friger M, Sukenik S, Buskila D. Clinical and radiographic outcomes of rheumatoid arthritis patients not treated with disease-modifying drugs. Arthritis Rheum. 1998; 41:1190–1195.

9. Flanagan ME, Blumenkopf TA, Brissette WH, Brown MF, Casavant JM, Shang-Poa C, Doty JL, Elliott EA, Fisher MB, Hines M, et al. Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection. J Med Chem. 2010; 53:8468–8484.

10. Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, Krishnaswami S, Burgos-Vargas R, Wilkinson B, Zerbini CA, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009; 60:1895–1905.

11. Coombs JH, Bloom BJ, Breedveld FC, Fletcher MP, Gruben D, Kremer JM, Burgos-Vargas R, Wilkinson B, Zerbini CA, Zwillich SH. Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2010; 69:413–416.

12. Ju W, Zhang M, Jiang JK, Thomas CJ, Oh U, Bryant BR, Chen J, Sato N, Tagaya Y, Morris JC, et al. CP-690,550, a therapeutic agent, inhibits cytokine-mediated Jak3 activation and proliferation of T cells from patients with ATL and HAM/TSP. Blood. 2011; 117:1938–1946.

13. Fleischmann R, Cutolo M, Genovese MC, Lee EB, Kanik KS, Sadis S, Connell CA, Gruben D, Krishnaswami S, Wallenstein G, et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying anti-rheumatic drugs. Arthritis Rheum. 2012; 64:617–629.

14. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315–324.

15. Van der Heijde D, Dankert T, Nieman F, Rau R, Boers M. Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis. Rheumatology (Oxford). 1999; 38:941–947.

16. Hulsmans HM, Jacobs JW, van der Heijde DM, van Albada-Kuipers GA, Schenk Y, Bijlsma JW. The course of radiologic damage during the first six years of rheumatoid arthritis. Arthritis Rheum. 2000; 43:1927–1940.

17. Sharp JT, Wolfe F, Mitchell DM, Bloch DA. The progression of erosion and joint space narrowing scores in rheumatoid arthritis during the first twenty-five years of disease. Arthritis Rheum. 1991; 34:660–668.

18. Tiippana-Kinnunen T, Laasonen L, Kautiainen H, Paimela L, Leirisalo-Repo M. Impact of early radiographic remission on the 15-year radiographic outcome in patients with rheumatoid arthritis. Scand J Rheumatol. 2011; 40:263–268.

19. Van der Heijde DM, van Leeuwen MA, van Riel PL, Koster AM, van't Hof AM, van Rijswijk MH, van de Putte LB. Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum. 1992; 35:26–34.

20. Dias EM, Lukas C, Landewé R, Fatenejad S, van der Heijde D. Reliability and sensitivity to change of the Simple Erosion Narrowing Score compared with the Sharp-van der Heijde method for scoring radiographs in rheumatoid arthritis. Ann Rheum Dis. 2008; 67:375–379.

21. Pincus T, Ferraccioli G, Sokka T, Larsen A, Rau R, Kushner I, Wolfe F. Evidence from clinical trials and long-term observational studies that disease-modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review. Rheumatology (Oxford). 2002; 41:1346–1356.

22. Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, Gruben D, Wallenstein GV, Zwillich SH, Kanik KS. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012; 367:495–507.

23. Van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, García Meijide JA, Wagner S, Forejtova S, Zwillich SH, Gruben D, Koncz T, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012; 367:508–519.

24. Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, Gruben D, Wallenstein G, Krishnaswami S, Zwillich SH, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013; 381:451–460.

25. Van der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, Cardiel MH, Cohen S, Nash P, Song YW, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum. 2013; 65:559–570.