PMID- 32506317
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2198-6576 (Print)
IS  - 2198-6584 (Electronic)
IS  - 2198-6576 (Linking)
VI  - 7
IP  - 3
DP  - 2020 Sep
TI  - Safety and Efficacy of Tofacitinib in Patients with Active Psoriatic Arthritis: 
      Interim Analysis of OPAL Balance, an Open-Label, Long-Term Extension Study.
PG  - 553-580
LID - 10.1007/s40744-020-00209-4 [doi]
AB  - INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of 
      psoriatic arthritis (PsA). We report the interim safety, tolerability, and 
      efficacy of tofacitinib in PsA patients in OPAL Balance, a 3-year, open-label, 
      long-term extension study (data cut-off: August 2017; database not locked, data 
      may change). METHODS: Eligible patients from two phase (P) 3 (P3) tofacitinib PsA 
      studies (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) entered OPAL 
      Balance </= 3 months after completing the P3 study or discontinuing for reasons 
      other than study-drug-related adverse events (AEs). Patients received open-label 
      tofacitinib 5 mg twice daily (BID), with adjustments to 10 mg BID permitted 
      post-month (M) 1. Certain concomitant conventional synthetic disease-modifying 
      antirheumatic drugs were allowed. Primary endpoints were incidence/severity of 
      AEs and laboratory abnormalities, and changes from baseline in laboratory 
      parameters (reported up to M36 and M30, respectively). Efficacy 
      (clinical/patient-reported outcomes) was reported through M30. RESULTS: A total 
      of 686 patients were treated; at data cut-off, 68.2% remained in the study. Mean 
      (range) treatment duration was 641 (1-1032) days; total treatment duration was 
      1153.2 patient-years. By M36, 79.6, 13.8, and 8.6% of patients reported AEs, 
      serious AEs, and discontinuations due to AEs, respectively. Five deaths occurred; 
      one within the risk period (incidence rate [IR; patients with events/100 
      patient-years] 0.1). IRs for AEs of special interest were: all (non-serious and 
      serious) herpes zoster, 1.7; serious infections, 0.9; opportunistic infections, 
      0.3 (all disseminated/multi-dermatomal herpes zoster); malignancies excluding 
      non-melanoma skin cancer (NMSC), 0.8; NMSC, 1.0; major adverse cardiovascular 
      events, 0.3; pulmonary embolisms, 0.1; and arterial thromboembolisms, 0.4. No 
      patients had deep vein thrombosis. Alanine aminotransferase and aspartate 
      aminotransferase levels were elevated  >/=  3-fold the upper limit of normal in 4.0 
      and 2.2% of patients, respectively. Changes in laboratory parameters were 
      generally stable over time, although lymphocyte counts decreased slightly. 
      Efficacy was maintained through M30. CONCLUSIONS: In this interim analysis of 
      OPAL Balance, tofacitinib safety and efficacy in patients with PsA appeared to be 
      consistent with those of the P3 studies. Efficacy was maintained over time. TRIAL 
      REGISTRATION: ClinicalTrials.gov identifier: NCT01976364.
FAU - Nash, Peter
AU  - Nash P
AD  - School of Medicine, Griffith University, Brisbane, QLD, Australia.
FAU - Coates, Laura C
AU  - Coates LC
AD  - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, 
      University of Oxford, Oxford, UK.
FAU - Kivitz, Alan J
AU  - Kivitz AJ
AD  - Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, 
      PA, USA.
FAU - Mease, Philip J
AU  - Mease PJ
AD  - Swedish Medical Center/Providence St Joseph Health and University of Washington, 
      Seattle, WA, USA.
FAU - Gladman, Dafna D
AU  - Gladman DD
AD  - Department of Medicine, University of Toronto and Krembil Research Institute, 
      Toronto Western Hospital, Toronto, ON, Canada.
FAU - Covarrubias-Cobos, Jose A
AU  - Covarrubias-Cobos JA
AD  - Unidad Rheumatologica Las Americas S.C.P, Merida, Mexico.
FAU - FitzGerald, Oliver
AU  - FitzGerald O
AD  - Conway Institute for Biomolecular Research, School of Medicine, University 
      College Dublin, Dublin, Ireland.
FAU - Fleishaker, Dona
AU  - Fleishaker D
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Wang, Cunshan
AU  - Wang C
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Wu, Joseph
AU  - Wu J
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Hsu, Ming-Ann
AU  - Hsu MA
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Menon, Sujatha
AU  - Menon S
AD  - Pfizer Inc, Groton, CT, USA.
FAU - Fallon, Lara
AU  - Fallon L
AD  - Pfizer Inc, Montreal, QC, Canada. lara.fallon@pfizer.com.
FAU - Romero, Ana Belen
AU  - Romero AB
AD  - Pfizer Inc, Barcelona, Spain.
FAU - Kanik, Keith S
AU  - Kanik KS
AD  - Pfizer Inc, Groton, CT, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01976364
PT  - Journal Article
DEP - 20200606
PL  - England
TA  - Rheumatol Ther
JT  - Rheumatology and therapy
JID - 101674543
PMC - PMC7410915
OAB - In many countries, tofacitinib is an approved medicine that can be used to treat 
      psoriatic arthritis (PsA). In the study reported here (OPAL Balance), adult 
      patients with PsA took tofacitinib for up to 3 years. We report a planned interim 
      analysis, i.e., an analysis of information collected before the study finished. 
      This early information suggests that the safety of tofacitinib, and how well it 
      improved symptoms and quality of life (efficacy), was similar in this long study 
      as in shorter studies. Information from the finished study will be reported 
      later. OPAL Balance started on 17 February 2014. This interim analysis includes 
      information collected by 31 August 2017. Before joining, patients had finished a 
      6-month or 12-month tofacitinib study (OPAL Broaden or OPAL Beyond). Patients in 
      OPAL Balance took a 5 mg tofacitinib pill twice a day, but if PsA symptoms did 
      not improve after 1 month, they could take a 10 mg pill twice a day. They could 
      also take other medicines (including methotrexate or corticosteroids). Of the 686 
      patients who took tofacitinib, 546 (80%) experienced side effects over 3 years. 
      These were considered serious for 95 patients (14%) and caused 59 patients (9%) 
      to leave the study. Five patients died from causes not related to tofacitinib. 
      Known tofacitinib side effects, including shingles (herpes zoster), serious 
      infections (needing hospitalization), infections in patients with weakened immune 
      systems, cancer, heart (cardiovascular) problems, and vein blockages (embolisms), 
      were each reported by fewer than 20 patients. Most blood test results and 
      tofacitinib efficacy were stable over 2.5 years.
OABL- eng
OTO - NOTNLM
OT  - Long-term extension
OT  - Psoriatic arthritis
OT  - Tofacitinib
EDAT- 2020/06/09 06:00
MHDA- 2020/06/09 06:01
PMCR- 2020/06/06
CRDT- 2020/06/08 06:00
PHST- 2020/02/21 00:00 [received]
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2020/06/09 06:01 [medline]
PHST- 2020/06/08 06:00 [entrez]
PHST- 2020/06/06 00:00 [pmc-release]
AID - 10.1007/s40744-020-00209-4 [pii]
AID - 209 [pii]
AID - 10.1007/s40744-020-00209-4 [doi]
PST - ppublish
SO  - Rheumatol Ther. 2020 Sep;7(3):553-580. doi: 10.1007/s40744-020-00209-4. Epub 2020 
      Jun 6.