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SAT0247 Impact of glucocorticoids on efficacy and safety of tofacitinib with and without methotrexate and adalimumab with methotrexate for rheumatoid arthritis: results from a phase 3b/4 randomised trial
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  1. R. Fleischmann1,
  2. J. Wollenhaupt2,
  3. S. Cohen1,
  4. J. S. Smolen3,
  5. P. Dahl4,
  6. N. Iikuni5,
  7. H. Shi6,
  8. S. Tatulych7,
  9. L. Takiya6
  1. 1Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX, United States
  2. 2Schön-Klinik Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg, Germany
  3. 3Medical University of Vienna and Heitzing Hospital, Vienna, Austria
  4. 4Pfizer Inc, Ballerup, Denmark
  5. 5Pfizer Inc, New York, NY
  6. 6Pfizer Inc, Collegeville, PA
  7. 7Pfizer Inc, Groton, CT, United States

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Glucocorticoids (GC) are an established therapy in RA that are often used to rapidly reduce pain and inflammation while awaiting the effects of disease-modifying antirheumatic drugs.

Objectives: A post hoc analysis to describe the impact of background GC on the efficacy and safety of tofacitinib with and without methotrexate (MTX) and adalimumab (ADA) with MTX in ORAL Strategy.

Methods: ORAL Strategy (NCT02187055) was a 1-year, double-blind, Phase 3b/4, head-to-head, non-inferiority randomised controlled trial in adult patients (pts) with active RA despite MTX therapy. Pts were randomised 1:1:1 to receive tofacitinib 5 mg twice daily (BID; tofa mono), tofacitinib 5 mg BID + MTX (tofa+MTX) or subcutaneous ADA 40 mg every other week + MTX (ADA+MTX). Pts receiving low-dose GC (≤10 mg/day prednisone or equivalent) before enrolment maintained a stable dose throughout the study period. The following efficacy endpoints were assessed through Month 12 for pts receiving tofa mono, tofa+MTX and ADA+MTX with/without GC: ACR20, ACR50 and ACR70 response rates, proportions of patients achieving low disease activity (LDA; DAS28–4[ESR]≤3.2) and remission (DAS28–4[ESR]<2.6) and change from baseline (BL) in HAQ-DI (ΔHAQ-DI). Safety endpoints were evaluated throughout the study and included adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs and serious infection events (SIEs).

Results: 1146 patients were randomised and treated; low-dose BL GC were received by 228/384 (59.4%) pts receiving tofa mono (mean [SD] BL GC dose: 7.5 [13.7] mg/day), 215/376 (57.2%) pts receiving tofa+MTX (mean [SD] BL GC dose: 6.5 [2.5] mg/day) and 223/386 (57.8%) pts receiving ADA+MTX (mean [SD] BL GC dose: 6.4 [2.6] mg/day). BL demographics and disease characteristics were generally similar across treatment groups, regardless of BL GC use. Efficacy endpoints (ACR50 response rate, LDA and remission rates, ΔHAQ-DI) were generally similar for each treatment group when stratified by GC use (figure 1, table 1; similar results were seen for ACR20/70 response rates – data not shown). GC use did not appear to be associated with higher rates of AEs, discontinuations due to AEs, SIEs and SAEs; some AE rates were higher with MTX than without MTX (table 2). SIEs in pts using GC included herpes zoster (HZ; tofa mono, n=2) and tuberculous meningitis (tofa+MTX, n=1); in pts not using GC, there was 1 event each of cytomegalovirus chorioretinitis (tofa+MTX), pulmonary TB (tofa+MTX), HZ (ADA+MTX) and varicella (ADA+MTX).

Figure 1

Proportion of patients achieving ACR50 response according to treatment group and GC use (FAS, with imputation*)

Table 1

Response rates in patients over 12 months, with or without baseline GC (FAS)

Table 2

Summary of AEs, discontinuations due to AEs, SAEs and SIEs over 12 months

Conclusions: In pts with RA, concomitant stable GC use did not appear to impact the efficacy of tofacitinib 5 mg BID±MTX or ADA+MTX. The finding that GC use was not associated with higher AE rates was unexpected and of interest.

Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by C Viegelmann of CMC and funded by Pfizer Inc.

Disclosure of Interest: R. Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, J. Wollenhaupt Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, S. Cohen Grant/research support from: AbbVie, Amgen, Astellas, Bristol-Meyers Squibb, Eli Lilly, Genentech, Gilead, Janssen, Novartis, Pfizer Inc, Roche, Sandoz, Consultant for: AbbVie, Amgen, Astellas, Bristol-Meyers Squibb, Eli Lilly, Genentech, Gilead, Janssen, Novartis, Pfizer Inc, Roche, Sandoz, J. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celltrion, Eli Lilly, GSK, ILTOO, Janssen, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celltrion, Eli Lilly, GSK, ILTOO, Janssen, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, P. Dahl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Tatulych Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

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