Article Text

Extended report
Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs
  1. Christina Charles-Schoeman1,
  2. Gerd Burmester2,
  3. Peter Nash3,4,
  4. Cristiano A F Zerbini5,
  5. Koshika Soma6,
  6. Kenneth Kwok7,
  7. Thijs Hendrikx8,
  8. Eustratios Bananis8,
  9. Roy Fleischmann9
  1. 1University of California, Los Angeles, California, USA
  2. 2Charité—University Medicine Berlin, Berlin, Germany
  3. 3Rheumatology Research Unit, Nambour Hospital, Sunshine Coast, Australia
  4. 4Department of Medicine, University of Queensland, Queensland, Australia
  5. 5Centro Paulista de Investigação Clinica, São Paulo, Brazil
  6. 6Pfizer Inc, Groton, Connecticut, USA
  7. 7Pfizer Inc, New York, New York, USA
  8. 8Pfizer Inc, Collegeville, Pennsylvania, USA
  9. 9Department of Medicine, Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  1. Correspondence to Dr Eustratios Bananis, US Medical Affairs, Inflammation & Immunology, Global Innovative Pharma, Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426, USA; stratis.bananis{at}


Objectives Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR).

Methods Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed.

Results 2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs).

Conclusions Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations.

  • DMARDs (biologic)
  • DMARDs (synthetic)
  • Rheumatoid Arthritis
  • Anti-TNF
  • Treatment

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