PMID- 33628334
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231110
IS  - 1756-2856 (Print)
IS  - 1756-2864 (Electronic)
IS  - 1756-2856 (Linking)
VI  - 14
DP  - 2021
TI  - Bioequivalence of intramuscular and subcutaneous peginterferon beta-1a: results 
      of a phase I, open-label crossover study in healthy volunteers.
PG  - 1756286420975227
LID - 10.1177/1756286420975227 [doi]
LID - 1756286420975227
AB  - BACKGROUND: Peginterferon beta-1a administered every 2 weeks via subcutaneous 
      (SC) injection is approved to treat adult patients with relapsing-remitting 
      multiple sclerosis (RRMS) and relapsing forms of multiple sclerosis (RMS). 
      However, associated injection site reactions (ISRs) can lead to treatment 
      discontinuation. Prior studies with interferon beta-1a reported a lower frequency 
      of ISRs with intramuscular (IM) administration than with SC administration. IM 
      administration of peginterferon beta-1a may therefore represent a useful 
      alternative treatment option. METHODS: A phase I, open-label, two-period 
      crossover study randomized healthy volunteers to receive a single dose of 
      peginterferon beta-1a 125 mcg administered IM followed by a single 125 mcg dose 
      administered SC after a 28-day washout or vice versa. Blood samples were 
      collected up to 504 h post dose to determine pharmacokinetic (PK) and 
      pharmacodynamic (PD) profiles. The primary endpoint was assessment of 
      bioequivalence based on maximum serum concentration (C(max)) and area under the 
      curve from time zero extrapolated to infinity (AUC(inf)). Other PK parameters, as 
      well as PD (serum neopterin) and safety profiles, were also evaluated. RESULTS: 
      The study enrolled 136 participants. Bioequivalence of IM and SC peginterferon 
      beta-1a was established for both C(max) ([least squares (LS)] mean IM/SC ratio: 
      1.083 [90% confidence interval (CI), 0.975-1.203]) and AUC(inf) (LS mean IM/SC 
      ratio: 1.089 [90% CI, 1.020-1.162]). Other PK and PD parameters were similar 
      between administration routes, although moderate to high inter-subject 
      variability was observed for IM and SC. Safety profiles were generally balanced 
      between IM and SC administration. ISRs occurred at a lower frequency with IM 
      [14.4% (95% CI, 8.89-21.56%)] than with SC [32.1% (95% CI, 24.29-40.70%)] 
      administration (p = 0.0005). CONCLUSIONS: These results demonstrate 
      bioequivalence between peginterferon beta-1a IM and SC and support the 
      consideration of IM injection of peginterferon beta-1a as a viable treatment 
      option in patients with RRMS and RMS.
CI  - (c) The Author(s), 2021.
FAU - Zhao, Yuan
AU  - Zhao Y
AD  - Biogen, Cambridge, MA, USA.
FAU - Chen, Kun
AU  - Chen K
AD  - Biogen, Cambridge, MA, USA.
FAU - Ramia, Nancy
AU  - Ramia N
AD  - Biogen, Cambridge, MA, USA.
FAU - Sahu, Sangeeta
AU  - Sahu S
AD  - Biogen, Cambridge, MA, USA.
FAU - Kumar, Achint
AU  - Kumar A
AD  - Biogen, Cambridge, MA, USA.
FAU - Naylor, Maria L
AU  - Naylor ML
AD  - Biogen, Cambridge, MA, USA.
FAU - Zhu, Li
AU  - Zhu L
AD  - Biogen, Cambridge, MA, USA.
FAU - Naik, Himanshu
AU  - Naik H
AD  - Biogen, Cambridge, MA, USA.
FAU - Butts, Cherie L
AU  - Butts CL
AD  - Biogen, 225 Binney St., Cambridge, MA 02142, USA.
LA  - eng
PT  - Journal Article
DEP - 20210122
PL  - England
TA  - Ther Adv Neurol Disord
JT  - Therapeutic advances in neurological disorders
JID - 101480242
PMC - PMC7883310
OTO - NOTNLM
OT  - administration route
OT  - bioequivalence
OT  - interferon beta
OT  - multiple sclerosis
OT  - peginterferon beta-1a
OT  - pegylated interferon
OT  - relapsing-remitting multiple sclerosis
COIS- Conflict of interest statement: YZ, NR, SS, AK, MLN, LZ, HN, and CLB are 
      employees of and may hold stock and/or stock options in Biogen. KC was an 
      employee of Biogen at the time of these analyses and may hold stock and/or stock 
      options in Biogen.
EDAT- 2021/02/26 06:00
MHDA- 2021/02/26 06:01
PMCR- 2021/01/22
CRDT- 2021/02/25 05:45
PHST- 2020/03/13 00:00 [received]
PHST- 2020/10/25 00:00 [accepted]
PHST- 2021/02/25 05:45 [entrez]
PHST- 2021/02/26 06:00 [pubmed]
PHST- 2021/02/26 06:01 [medline]
PHST- 2021/01/22 00:00 [pmc-release]
AID - 10.1177_1756286420975227 [pii]
AID - 10.1177/1756286420975227 [doi]
PST - epublish
SO  - Ther Adv Neurol Disord. 2021 Jan 22;14:1756286420975227. doi: 
      10.1177/1756286420975227. eCollection 2021.