title: Efficacy and safety of tofacitinib in older and younger patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the efficacy and safety of tofacitinib 5 or 10 mg twice daily (BID), in patients with moderate to severe RA, aged ≥65 and <65 years.
  
  
  METHODS
  Data were pooled from five Phase 3 trials and, separately, from two open-label long-term extension (LTE) studies (data cut-off April, 2012). Patients received tofacitinib, or placebo (Phase 3 only), with/without conventional synthetic DMARDs (mainly methotrexate). Clinical efficacy outcomes from Phase 3 studies were evaluated at Month 3. Safety evaluations using pooled Phase 3 data (Month 12) and pooled LTE data (Month 24) compared exposure-adjusted incidence rates (IRs; with 95% confidence intervals [CIs]), in older versus younger patients.
  
  
  RESULTS
  In Phase 3 and LTE studies, 15.3% (475/3111) and 16.1% (661/4102) of patients, respectively, were aged ≥65 years. Consequently, exposure to tofacitinib was lower in older versus younger patients in Phase 3 (259.2 vs. 1554.9 patient years [pt-yrs]) and LTE (962.1 vs. 5071.7 pt-yrs) studies. Probability ratios for ACR responses and HAQ-DI improvement from baseline ≥0.22 (Month 3) favoured tofacitinib and were similar in older and younger patients, with overlapping CIs. IRs for SAEs and discontinuations due to AEs were generally numerically higher in older versus younger patients, irrespective of treatment.
  
  
  CONCLUSIONS
  Older patients receiving tofacitinib 5 or 10 mg BID had a similar probability of ACR20 or ACR50 response and, due to comorbidities, a numerically higher risk of SAEs and discontinuations due to AEs compared with younger patients.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine IV, University of Munich, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schulze-Koops
authors.affiliation: Pfizer Inc, Collegeville, PA, USA. liza.takiya@pfizer.com.
authors.forename: Liza
authors.initials: L
authors.lastname: Takiya
authors.affiliation: Pfizer, Inc, Groton, CT, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mebus
authors.affiliation: Pfizer, Inc, Groton, CT, USA.
authors.forename: Ketti K
authors.initials: KK
authors.lastname: Terry
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Biswas
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Jones
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D017326:Clinical Trials, Phase III as Topic; D015897:Comorbidity; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053612:Janus Kinases