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THU0180 Lack of Early Change in Disease Activity Score Predicts The Likelihood of Achieving Low Disease Activity at Month 6: Tofacitinib Monotherapy versus Methotrexate in Methotrexate-Naïve Patients with Rheumatoid Arthritis
  1. E. Keystone1,
  2. R.F. van Vollenhoven2,
  3. B. Wilkinson3,
  4. L. Fallon4,
  5. L.-J. Hwang5,
  6. D. Chapman5,
  7. R. DeMasi5,
  8. E.B. Lee6
  1. 1Mount Sinai Hospital, Toronto, Canada
  2. 2Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands
  3. 3Pfizer Inc, Groton, United States
  4. 4Pfizer Canada, Montreal, Canada
  5. 5Pfizer Inc, New York, United States
  6. 6Seoul National University, Seoul, Korea, Republic Of

Abstract

Background Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Treatment guidelines recommend targeting remission or low disease activity (LDA), herein defined as Disease Activity Scores ≤3.2 based on 28 joint counts (DAS28≤3.2) and adjusting therapy after 3–6 months1 (Mos). Predicting the likelihood of clinical response may help inform early treatment decisions.

Objectives To understand the relationship between timing and magnitude of early changes in DAS28, erythrocyte sedimentation rate (DAS28-4[ESR]) and the likelihood of achieving LDA at Mo 6 in RA patients (pts) naïve to methotrexate (MTX).

Methods In a Phase 3 study (ORAL Start; NCT01039688), MTX-naïve RA pts were randomised 2:2:1 to the following monotherapies: tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or MTX. Conditional probability of pts achieving LDA at Mo 6 were calculated, given failure to achieve DAS28-4(ESR) improvement from baseline (range ≥0.3 to 1.8) at Mo 1 or 3. One-year data with non-responder imputation for missing values was used.

Results 948 pts received treatment; tofacitinib 5 mg BID (n=370), tofacitinib 10 mg BID (n=394) or MTX (n=184); results previously reported.2 In this post-hoc analysis, of those patients who failed to achieve DAS28-4(ESR) improvement from baseline ≥1.2 at Mo 3, 6.8% for tofacitinib 5 mg BID, 11.3% for tofacitinib 10 mg BID and 6.2% for MTX achieved LDA at Mo 6 (Table). A minority of pts (74/353 [20.9%]) receiving tofacitinib 5 mg BID failed to achieve DAS28-4(ESR) improvement ≥1.2 from baseline at Mo 3, while a greater proportion failed for MTX (65/171 [38.0%]). Failure to achieve DAS28-4(ESR) improvement from baseline at Mo 3 (range ≥0.30–1.8) for tofacitinib 5 mg BID and MTX was associated with a low probability (≤10%) of achieving LDA at Mo 6. For tofacitinib 5 mg BID, failure to achieve lower thresholds of DAS28-4(ESR) improvement (range ≥0.3 to 0.9) at Mo 1 was associated with lower probability of LDA at Mo 6 than higher DAS28-4(ESR) thresholds (≥1.2–1.8) (Table).

Conclusions Failure to achieve DAS28-4(ESR) improvement ≥1.2 from baseline at Mo 3 was associated with a low probability of achieving LDA at Mo 6 (≤6.8%) for tofacitinib 5 mg BID and MTX. For the minority of MTX-naïve RA pts treated with tofacitinib 5 mg BID or MTX who failed to achieve a minimal clinical response (DAS28-4[ESR] improvement ≥1.2) by Mo 3, another treatment option can be considered at Mo 3, as there is a low probability of reaching LDA at Mo 6.

  1. Smolen J et al. Ann Rheum Dis 2016;75(1):3–15.

  2. Lee EB et al. N Engl J Med 2014;370:2377–2386.

Acknowledgement This study was sponsored by Pfizer Inc. Editorial support was provided by Rebecca Bright, PhD, of Complete Medical Communications, and funded by Pfizer Inc.

Disclosure of Interest E. Keystone Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, R. F. van Vollenhoven Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, B. Wilkinson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L.-J. Hwang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. B. Lee Consultant for: Pfizer Inc

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