PMID- 32710493
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2578-5745 (Electronic)
IS  - 2578-5745 (Linking)
VI  - 2
IP  - 8
DP  - 2020 Aug
TI  - Long-Term Safety and Tolerability of Apremilast Versus Placebo in Psoriatic 
      Arthritis: A Pooled Safety Analysis of Three Phase III, Randomized, Controlled 
      Trials.
PG  - 459-470
LID - 10.1002/acr2.11156 [doi]
AB  - OBJECTIVE: Psoriatic arthritis (PsA) requires long-term treatment, yet safety 
      concerns and monitoring requirements make maintenance a challenge. This analysis 
      of pooled Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) 
      1, 2, and 3 data describes 3-year apremilast safety and tolerability in PsA. 
      METHODS: Patients with active PsA were randomized (1:1:1) to placebo, apremilast 
      30 mg twice daily, or apremilast 20 mg twice daily. Placebo patients were 
      re-randomized to apremilast 30 mg twice daily or 20 mg twice daily at week 16 
      (early escape) or 24. Double-blind treatment continued to week 52; patients could 
      continue apremilast during an open-label, long-term treatment phase. RESULTS: In 
      total, 1493 patients received at least one dose of study medication and were 
      included in the safety population (placebo: n = 495; apremilast 30 mg: n = 497; 
      apremilast 20 mg: n = 501). Among patients receiving apremilast, 53.2% (767/1441) 
      completed 3 years of treatment. Greater rates of adverse events (AEs) were 
      reported with apremilast (61.1%; exposure-adjusted incidence rate [EAIR]/100 
      patient-years, 265.1) versus placebo (47.5%; EAIR/100 patient-years, 200.7) in 
      the placebo-controlled period. During weeks 0 to </=52, the most common AEs 
      occurring in apremilast-exposed patients were diarrhea (13.9%; EAIR/100 
      patient-years, 18.6), nausea (12.3%; EAIR/100 patient-years, 16.0), headache 
      (9.4%; EAIR/100 patient-years, 12.1), upper respiratory tract infection (9.1%; 
      EAIR/100 patient-years, 11.5), and nasopharyngitis (6.2%; EAIR/100 patient-years, 
      7.7). Most AEs were mild/moderate with apremilast exposure </=156 weeks. Rates of 
      depression remained low (EAIR/100 patient-years, 1.8). Major adverse cardiac 
      events (EAIR/100 patient-years, 0.5), malignancies (EAIR/100 patient-years, 0.9), 
      and serious opportunistic infections (EAIR/100 patient-years, 0.0) were 
      infrequent over the 3-year exposure period. Discontinuation rates due to AEs were 
      low (<7.5%) across all apremilast-exposure periods. Incidences of clinically 
      meaningful abnormalities in postbaseline laboratory values was low; most values 
      returned to baseline levels with continued treatment and without intervention. 
      CONCLUSION: Apremilast demonstrated a favorable safety profile and was well 
      tolerated up to 156 weeks.
CI  - (c) 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on 
      behalf of American College of Rheumatology.
FAU - Mease, Philip J
AU  - Mease PJ
AD  - Swedish Medical Center/Providence St. Joseph Health, Seattle, Washington and 
      University of Washington School of Medicine, Seattle.
FAU - Gladman, Dafna D
AU  - Gladman DD
AD  - Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada.
FAU - Gomez-Reino, Juan J
AU  - Gomez-Reino JJ
AD  - Fundacion Dominguez, Hospital Clinico Universitario, Santiago, Spain.
FAU - Hall, Stephen
AU  - Hall S
AD  - Monash University, Cabrini Health, Melbourne, Australia.
FAU - Kavanaugh, Arthur
AU  - Kavanaugh A
AD  - University of California San Diego School of Medicine, La Jolla.
FAU - Lespessailles, Eric
AU  - Lespessailles E
AD  - Regional Hospital, University of Orleans, Orleans, France.
FAU - Schett, Georg
AU  - Schett G
AUID- ORCID: 0000-0001-8740-9615
AD  - Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany und 
      Universitatsklinikum Erlangen, Erlangen, Germany.
FAU - Paris, Maria
AU  - Paris M
AD  - Amgen Inc, Thousand Oaks, California.
FAU - Delev, Nikolay
AU  - Delev N
AD  - Celgene Corporation, Summit, New Jersey.
FAU - Teng, Lichen
AU  - Teng L
AD  - Amgen Inc, Thousand Oaks, California.
FAU - Wollenhaupt, Jurgen
AU  - Wollenhaupt J
AD  - Jurgen Wollenhaupt: Schon Klinik Hamburg Eilbek, Hamburg, Germany.
LA  - eng
GR  - Celgene/
PT  - Journal Article
DEP - 20200725
PL  - United States
TA  - ACR Open Rheumatol
JT  - ACR open rheumatology
JID - 101740025
PMC - PMC7437129
EDAT- 2020/07/28 06:00
MHDA- 2020/07/28 06:01
PMCR- 2020/07/25
CRDT- 2020/07/26 06:00
PHST- 2019/07/30 00:00 [received]
PHST- 2020/03/23 00:00 [accepted]
PHST- 2020/07/28 06:00 [pubmed]
PHST- 2020/07/28 06:01 [medline]
PHST- 2020/07/26 06:00 [entrez]
PHST- 2020/07/25 00:00 [pmc-release]
AID - ACR211156 [pii]
AID - 10.1002/acr2.11156 [doi]
PST - ppublish
SO  - ACR Open Rheumatol. 2020 Aug;2(8):459-470. doi: 10.1002/acr2.11156. Epub 2020 Jul 
      25.