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THU0195 Consistent efficacy and safety of tofacitinib in rheumatoid arthritis patients with inadequate response or intolerance to NON-MTX csdmards
  1. J Tesser1,
  2. A Gül2,
  3. E Olech3,
  4. K Oelke4,
  5. T Lukic5,
  6. CW Murray6,
  7. C Zhang6,
  8. L Takiya6
  1. 1Arizona Arthritis & Rheumatology Associates, Glendale, AZ, United States
  2. 2Istanbul University, Istanbul, Turkey
  3. 3UNLV School of Medicine, Las Legas, NV
  4. 4Rheumatic Disease Center, Glendale, WI
  5. 5Pfizer Inc, New York, NY
  6. 6Pfizer Inc, Collegeville, PA, United States

Abstract

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. In clinical practice, a proportion of patients (pts) with RA may not be candidates for treatment with the conventional synthetic DMARD (csDMARD) methotrexate (MTX).1

Objectives To evaluate tofacitinib 5 or 10 mg BID efficacy and safety using pooled data from 8 Phase (P) 2 and 6 P3 trials in RA pts who were (1) inadequate responders (IR)/intolerant to csDMARDs, but did not have an IR or intolerance to MTX or biologic DMARDs (ie, non-MTX csDMARD-IR population) or (2) pts with an IR/intolerance to any csDMARD including MTX but not bDMARD-IR (ie, 2nd-line population).

Methods Month 3 efficacy outcomes included proportions of pts achieving ACR20/50/70 responses, and Disease Activity Score 28-4(ESR) (DAS28-4[ESR])<2.6 (remission), as well as change from baseline in DAS28-4(ESR) and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. No multiplicity adjustments were made. Crude incidence rates (CIR; unique pts with events/100 pt-years) based on adverse event (AE) reporting through Month 24 were calculated for treatment-emergent AEs (TEAEs), serious AEs (SAEs), discontinuations (DCs) due to AEs and AEs of special interest.

Results In the P2/3 tofacitinib RA trials, prior csDMARDs received by the non-MTX csDMARD-IR and 2nd-line populations, respectively were: chloroquine (17.7% and 37.2%), hydroxychloroquine (13.7% and 22.7%), leflunomide (19.4% and 20.9%), MTX (7.3% and 93.3%), sulfasalazine (31.1% and 27.1%) and others (8.0% and 11.1%); pts may have received >1 prior csDMARD. The non-MTX csDMARD-IR population included 208, 247 and 82 pts receiving tofacitinib 5 and 10 mg BID or placebo (PBO), respectively; the 2nd-line population comprised 1206, 1266 and 856 pts, respectively. Baseline characteristics were generally similar between populations except for mean RA duration (5.2–7.2 years, non-MTX csDMARD-IR pts; 8.2–8.5 years, 2nd-line pts). Most pts were female (80.3–85.4%), mean age range was 49.7–52.5 years and mean DAS28-4(ESR) score ranged from 6.2–6.5. Tofacitinib 5 and 10 mg BID achieved higher ACR responses and greater changes from baseline in DAS28-4(ESR) and HAQ-DI scores vs PBO at Month 3 in both populations (Table). Numerically higher proportions of non-MTX csDMARD-IR pts achieved efficacy outcomes vs 2nd-line population. CIRs for SAEs, DCs due to AEs and AEs of special interest were similar across groups; CIRs for TEAEs were higher with PBO vs tofacitinib. AE frequency was generally lower in the non-MTX csDMARD-IR population vs 2nd-line population.

Conclusions This analysis indicates that tofacitinib is associated with similar efficacy and safety outcomes between csDMARD-IR (including MTX-IR) pts and those who are csDMARD-IR but not MTX-IR. This suggests a favourable tofacitinib benefit/risk profile for RA pts who have a contraindication to or refuse treatment with MTX and failed other csDMARDs.

References

  1. Lopez-Olivo MA et al. Cochrane Database Syst Rev 2014; CD000957.

References

Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by K Nicholson of CMC and was funded by Pfizer Inc.

Disclosure of Interest J. Tesser Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, A. Gül Consultant for: AbbVie, Bristol-Myers Squibb, MSD, Novartis, Pfizer Inc, Roche, Servier, UCB, Xoma, E. Olech Grant/research support from: AbbVie, Amgen, Celgene, Genentech, Janssen, Regeneron, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Consultant for: AbbVie, Amgen, Celgene, Genentech, Janssen, Regeneron, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, K. Oelke Grant/research support from: Novartis, Consultant for: Novartis, Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb, Pfizer Inc, Crescendo Biosciences, UCB, T. Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Murray Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Consultant for: Pfizer Inc

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