Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

Roy M Fleischmann, Tom W J Huizinga, Arthur F Kavanaugh, Bethanie Wilkinson, Kenneth Kwok, Ryan DeMasi, Ronald F van Vollenhoven, Roy M Fleischmann, Tom W J Huizinga, Arthur F Kavanaugh, Bethanie Wilkinson, Kenneth Kwok, Ryan DeMasi, Ronald F van Vollenhoven

Abstract

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA.

Methods: MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial.

Results: Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed.

Conclusions: Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA.

Trial registration number: NCT01039688; Results.

Keywords: DMARDs (synthetic); Early Rheumatoid Arthritis; Methotrexate; Rheumatoid Arthritis.

Figures

Figure 1
Figure 1
Clinical response in patients with early and established RA at month 24. *p

Figure 2

Radiographic parameters assessed at month…

Figure 2

Radiographic parameters assessed at month 24 in patients with early RA and established…

Figure 2
Radiographic parameters assessed at month 24 in patients with early RA and established RA. *p

Figure 3

Treatment differences versus MTX in…

Figure 3

Treatment differences versus MTX in patients with early and established RA at month…

Figure 3
Treatment differences versus MTX in patients with early and established RA at month 24. (A and B) tofacitinib 5 mg two times a day; (C and D) tofacitinib 10 mg two times a day. Early and established RA are defined as disease duration

Figure 4

Clinical and radiographic end points…

Figure 4

Clinical and radiographic end points ORs at month 24 for patients with early…

Figure 4
Clinical and radiographic end points ORs at month 24 for patients with early and established RA. (A) tofacitinib 5 mg two times a day; (B) tofacitinib 10 mg two times a day; (C) MTX. Early and established RA are defined as disease duration
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References
    1. Shah A. Harrison's Principle of Internal Medicine. 18th edn USA: McGraw Hill, 2012:2749.
    1. Singh JA, Furst DE, Bharat A et al. . 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:625–39. 10.1002/acr.21641 - DOI - PMC - PubMed
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Figure 2
Figure 2
Radiographic parameters assessed at month 24 in patients with early RA and established RA. *p

Figure 3

Treatment differences versus MTX in…

Figure 3

Treatment differences versus MTX in patients with early and established RA at month…

Figure 3
Treatment differences versus MTX in patients with early and established RA at month 24. (A and B) tofacitinib 5 mg two times a day; (C and D) tofacitinib 10 mg two times a day. Early and established RA are defined as disease duration

Figure 4

Clinical and radiographic end points…

Figure 4

Clinical and radiographic end points ORs at month 24 for patients with early…

Figure 4
Clinical and radiographic end points ORs at month 24 for patients with early and established RA. (A) tofacitinib 5 mg two times a day; (B) tofacitinib 10 mg two times a day; (C) MTX. Early and established RA are defined as disease duration
Similar articles
Cited by
References
    1. Shah A. Harrison's Principle of Internal Medicine. 18th edn USA: McGraw Hill, 2012:2749.
    1. Singh JA, Furst DE, Bharat A et al. . 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:625–39. 10.1002/acr.21641 - DOI - PMC - PubMed
    1. Bathon JM, Martin RW, Fleischmann RM et al. . A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586–93. 10.1056/NEJM200011303432201 - DOI - PubMed
    1. Genovese MC, Bathon JM, Martin RW et al. . Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 2002;46:1443–50. 10.1002/art.10308 - DOI - PubMed
    1. St Clair EW, van der Heijde DM, Smolen JS et al. . Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004;50:3432–43. 10.1002/art.20568 - DOI - PubMed
Show all 34 references
Associated data
Related information
LinkOut - more resources
Full text links [x]
[x]
Cite
Copy Download .nbib .nbib
Format: AMA APA MLA NLM

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

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Figure 3
Figure 3
Treatment differences versus MTX in patients with early and established RA at month 24. (A and B) tofacitinib 5 mg two times a day; (C and D) tofacitinib 10 mg two times a day. Early and established RA are defined as disease duration

Figure 4

Clinical and radiographic end points…

Figure 4

Clinical and radiographic end points ORs at month 24 for patients with early…

Figure 4
Clinical and radiographic end points ORs at month 24 for patients with early and established RA. (A) tofacitinib 5 mg two times a day; (B) tofacitinib 10 mg two times a day; (C) MTX. Early and established RA are defined as disease duration
Similar articles
Cited by
References
    1. Shah A. Harrison's Principle of Internal Medicine. 18th edn USA: McGraw Hill, 2012:2749.
    1. Singh JA, Furst DE, Bharat A et al. . 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:625–39. 10.1002/acr.21641 - DOI - PMC - PubMed
    1. Bathon JM, Martin RW, Fleischmann RM et al. . A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586–93. 10.1056/NEJM200011303432201 - DOI - PubMed
    1. Genovese MC, Bathon JM, Martin RW et al. . Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 2002;46:1443–50. 10.1002/art.10308 - DOI - PubMed
    1. St Clair EW, van der Heijde DM, Smolen JS et al. . Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004;50:3432–43. 10.1002/art.20568 - DOI - PubMed
Show all 34 references
Associated data
Related information
LinkOut - more resources
Full text links [x]
[x]
Cite
Copy Download .nbib .nbib
Format: AMA APA MLA NLM
Figure 4
Figure 4
Clinical and radiographic end points ORs at month 24 for patients with early and established RA. (A) tofacitinib 5 mg two times a day; (B) tofacitinib 10 mg two times a day; (C) MTX. Early and established RA are defined as disease duration

References

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    1. Bathon JM, Martin RW, Fleischmann RM et al. . A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586–93. 10.1056/NEJM200011303432201
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