You are here

Article Text

Article menu
XML
Letter
Age-based (<65 vs ≥65 years) incidence of infections and serious infections with tofacitinib versus biological DMARDs in rheumatoid arthritis clinical trials and the US Corrona RA registry
  1. Kevin L Winthrop1,
  2. Gustavo Citera2,
  3. David Gold3,
  4. Dan Henrohn4,
  5. Carol A Connell5,
  6. Andrea B Shapiro6,
  7. Harry Shi7,
  8. Alina M Onofrei8,
  9. Dimitrios A Pappas9,
  10. Hendrik Schulze-Koops10
  1. 1 Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon, USA
  2. 2 Section of Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina
  3. 3 Pfizer Inc, Montreal, Quebec, Canada
  4. 4 Pfizer Inc, Sollentuna, Sweden
  5. 5 Pfizer Inc, Groton, Connecticut, USA
  6. 6 Pfizer Inc, Peapack, New Jersey, USA
  7. 7 Pfizer Inc, Collegeville, Pennsylvania, USA
  8. 8 Corrona LLC, Waltham, Massachusetts, USA
  9. 9 Department of Medicine, Columbia University, New York, New York, USA
  10. 10 Division of Rheumatology and Clinical Immunology, Department of Internal Medicine IV, University of Munich, Munich, Bayern, Germany
  1. Correspondence to Dr David Gold, Pfizer Inc, Montreal, QC H9J 2M5, Canada; David.Gold{at}pfizer.com

https://doi.org/10.1136/annrheumdis-2020-218992

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    A randomised, open-label, blinded endpoint post-authorisation safety study (Study A3921133; NCT02092467; database not locked and subject to change) evaluated the safety of tofacitinib 5 mg and 10 mg twice daily (BID) versus tumour necrosis factor inhibitors (TNFi) (adalimumab/etanercept) in rheumatoid arthritis (RA) patients aged ≥50 years with ≥1 cardiovascular risk factor. An ad hoc interim safety analysis of Study A3921133 reported incidence rates (IRs) per 100 patient-years (95% CIs) for fatal infections (within 28 days of treatment) and non-fatal serious infection events (SIEs), respectively: tofacitinib 5 mg BID, 0.18 (0.07 to 0.39) and 3.35 (2.78 to 4.01); tofacitinib 10 mg BID, 0.22 (0.09 to 0.46) and 3.51 (2.93 to 4.16); TNFi, 0.06 (0.01 to 0.22) and 2.79 (2.28 to 3.39).1 SIEs risk (fatal/non-fatal) was further increased with tofacitinib in patients aged >65 years versus younger patients; therefore, the European Medicines Agency recommended that older patients should receive tofacitinib when there is no suitable alternative treatment.2

    Further to these recommendations, we sought to assess age-based (<65 vs ≥65 years) SIE risk in RA patients receiving tofacitinib in Phase 2, 3 and 3b/4 tofacitinib studies with a TNFi control/comparator arm,3–5 and in the US Corrona RA registry.

    The clinical data set included 2180 patients (tofacitinib 5 mg BID, n=1064 (943.4 patient-years); tofacitinib 10 mg BID, n=306 (236.6 patient-years); adalimumab, n=643 (554.3 patient-years); placebo, n=167 (108.1 patient-years)). Overall, 1841 (84.4%) patients were aged <65 years and 339 (15.6%) ≥65 years. Crude IRs (patients with events/100 patient-years) and HRs were calculated for all first infections and first SIEs, overall and by age.

    For all infections (online supplemental figure S1), IRs and infection risk (by HRs) were higher with active treatments versus placebo, and similar across active treatments and age groups. For SIEs (figure 1), IRs were higher in older versus younger patients for active treatments, …

    View Full Text

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.