PMID- 34563243
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 23
IP  - 1
DP  - 2021 Sep 25
TI  - Long-term efficacy, safety, and immunogenicity of the adalimumab biosimilar, 
      PF-06410293, in patients with rheumatoid arthritis after switching from reference 
      adalimumab (Humira(R)) or continuing biosimilar therapy: week 52-92 data from a 
      randomized, double-blind, phase 3 trial.
PG  - 248
LID - 10.1186/s13075-021-02626-4 [doi]
LID - 248
AB  - BACKGROUND/OBJECTIVE: REFLECTIONS B538-02 is a randomized, double-blind 
      comparative study of the adalimumab (ADL) biosimilar PF-06410293, (ADL-PF), and 
      reference ADL sourced from the European Union (ADL-EU) in patients with active 
      RA. Therapeutic equivalence was demonstrated based on ACR20 responses at week 12 
      (primary endpoint). We report long-term safety, immunogenicity, and efficacy of 
      ADL-PF in patients who continued ADL-PF treatment throughout 78 weeks or who 
      switched from ADL-EU to ADL-PF at week 26 or week 52. METHODS: Eligible patients 
      (2010 ACR/EULAR RA diagnosis criteria for >/= 4 months; inadequate response to MTX, 
      </= 2 doses non-ADL biologic), stratified by geographic regions were initially 
      randomized (1:1) in treatment period 1 (TP1) to ADL-PF or ADL-EU (40 mg 
      subcutaneously, biweekly), both with MTX (10-25 mg/week). At week 26 (start of 
      TP2), patients receiving ADL-EU were re-randomized to remain on ADL-EU or 
      transition to ADL-PF for 26 weeks. At week 52 (start of TP3), all patients 
      received open-label treatment with ADL-PF for 26 weeks and were followed after 
      last treatment dose to week 92. To evaluate maintenance of response after 
      switching or remaining on ADL-PF, ACR20, DAS28-4(CRP), and other measures of 
      clinical response/remission were assessed through week 78 as secondary endpoints. 
      Three groups were evaluated: biosimilar, week 26 switch, and week 52 switch. 
      RESULTS: Overall, 507 patients participated in TP3. ACR20 response rates at week 
      52 were 88.4%, 88.2%, and 87.6% for the biosimilar, week 26, and week 52 switch 
      groups, respectively. ACR20 response rates and DAS28-4(CRP) scores were sustained 
      and comparable across groups in TP3. Incidence of treatment-emergent adverse 
      events (AEs) during TP3 and follow-up was 42.6% (biosimilar), 37.0% (week 26 
      switch), and 50.8% (week 52 switch); 3 (0.6%) patients (all week 52 switch) 
      reported treatment-related serious AEs. ADL-PF was generally well tolerated, with 
      a comparable safety profile across groups. Overall, incidences of patients with 
      anti-drug antibodies in TP3 and follow-up were comparable among groups (46.1%, 
      46.5%, and 54.2%, respectively). CONCLUSIONS: There were no clinically meaningful 
      differences in safety, immunogenicity, and efficacy for patients who were 
      maintained on ADL-PF for 78 weeks and those who had switched from ADL-EU at week 
      26 or week 52. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02480153. First posted 
      on June 24, 2015; EU Clinical Trials Register; EudraCT number: 2014-000352-29. 
      Start date, October 27, 2014.
CI  - (c) 2021. The Author(s).
FAU - Fleischmann, Roy M
AU  - Fleischmann RM
AUID- ORCID: 0000-0002-6630-1477
AD  - University of Texas Southwestern Medical Center at Dallas, Metroplex Clinical 
      Research Center, Dallas, TX, USA. RFleischmann@arthdocs.com.
FAU - Alvarez, Daniel F
AU  - Alvarez DF
AD  - Pfizer Inc., Collegeville, PA, USA.
FAU - Bock, Amy E
AU  - Bock AE
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Cronenberger, Carol
AU  - Cronenberger C
AD  - Pfizer Inc., Collegeville, PA, USA.
FAU - Vranic, Ivana
AU  - Vranic I
AD  - Pfizer, Tadworth, UK.
FAU - Zhang, Wuyan
AU  - Zhang W
AD  - Pfizer Inc., Lake Forest, IL, USA.
FAU - Alten, Rieke
AU  - Alten R
AD  - Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT02480153
SI  - EudraCT/2014-000352-29
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210925
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Biosimilar Pharmaceuticals)
RN  - 0 (PF-06410293)
RN  - FYS6T7F842 (Adalimumab)
SB  - IM
MH  - Adalimumab/adverse effects
MH  - *Antirheumatic Agents/adverse effects
MH  - *Arthritis, Rheumatoid/diagnosis/drug therapy
MH  - *Biosimilar Pharmaceuticals/adverse effects
MH  - Double-Blind Method
MH  - Humans
MH  - Treatment Outcome
PMC - PMC8464121
OTO - NOTNLM
OT  - Adalimumab
OT  - Adalimumab-afzb
OT  - Biosimilar
OT  - Long-term
OT  - PF-06410293
OT  - Rheumatoid arthritis
OT  - Safety
OT  - Switch
COIS- DFA, AEB, and IV are full-time employees of, and declare shareholdings, stock 
      holdings, and/or stock options from, Pfizer. CC was a full-time employee of 
      Pfizer at the time of data generation and manuscript development and declares 
      shareholdings, stock holdings, and/or stock options from Pfizer. WZ is a 
      full-time employee of Pfizer and declares shareholdings, stock holdings, and/or 
      stock options from Pfizer, AbbVie, and Abbott. RMF has received research 
      grants/support and consulting fees from Pfizer. RA has received research 
      grants/support and consulting fees from AbbVie, Bristol-Myers Squibb, Gilead, 
      Lilly, Novartis, Pfizer, and UCB.
EDAT- 2021/09/27 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/09/25
CRDT- 2021/09/26 20:28
PHST- 2021/04/09 00:00 [received]
PHST- 2021/09/12 00:00 [accepted]
PHST- 2021/09/26 20:28 [entrez]
PHST- 2021/09/27 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/09/25 00:00 [pmc-release]
AID - 10.1186/s13075-021-02626-4 [pii]
AID - 2626 [pii]
AID - 10.1186/s13075-021-02626-4 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2021 Sep 25;23(1):248. doi: 10.1186/s13075-021-02626-4.