Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment

An integrated analysis of Phases 2 and 3 trials

Masayoshi Harigai, Tsutomu Takeuchi, Josef S. Smolen, Kevin Winthrop, Atsushi Nishikawa, Terence P. Rooney, Chadi G. Saifan, Maher Issa, Yoshitaka Isaka, Naotsugu Akashi, Taeko Ishii, Yoshiya Tanaka

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: Baricitinib is a selective oral inhibitor of JAK1/JAK2 for patients with moderately-to-severely active rheumatoid arthritis (RA). Baricitinib’s safety profile in Japanese patients was evaluated using six studies (five Ph2/Ph3 trials, one long-term extension study through 01 September 2016) from an integrated database (nine RA studies). Methods: Incidence rates (IRs) or exposure-adjusted IRs (EAIRs) of adverse events (AEs) per 100 patient-years (PY) were calculated using data which included RA patients exposed to any baricitinib dose. Results: Five hundred and fourteen Japanese patients received baricitinib for 851.5 total PY of exposure (median 1.7 years, maximum 3.2). The EAIR of treatment-emergent AEs was 57.4/100PY. There were no deaths; 31 patients had serious infections (IR: 3.6/100PY), 55 herpes zoster (6.5), 0 tuberculosis, 10 malignancies (1.1) including two lymphomas, two major cardiovascular AEs (0.3), one gastrointestinal perforation (0.1), and four deep vein thrombosis (0.5). In Japanese patients, herpes zoster was more frequent than that of patients overall in the integrated database, but the events were considered manageable. Conclusion: In this analysis, baricitinib had acceptable safety profile in Japanese RA patients in the context of demonstrated efficacy. Aside from herpes zoster, baricitinib safety was not notably different between Japanese RA patients and those RA patients in the integrated database. Trial registration: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and NCT01885078 at https://clinicaltrials.gov/.

Original languageEnglish (US)
JournalModern Rheumatology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Rheumatoid Arthritis
Safety
Herpes Zoster
Therapeutics
Databases
baricitinib
Incidence
Venous Thrombosis
Lymphoma
Tuberculosis
Infection

Keywords

  • Baricitinib
  • Janus kinase (JAK)
  • Japanese
  • rheumatoid arthritis
  • safety

ASJC Scopus subject areas

  • Rheumatology

Cite this

Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment : An integrated analysis of Phases 2 and 3 trials. / Harigai, Masayoshi; Takeuchi, Tsutomu; Smolen, Josef S.; Winthrop, Kevin; Nishikawa, Atsushi; Rooney, Terence P.; Saifan, Chadi G.; Issa, Maher; Isaka, Yoshitaka; Akashi, Naotsugu; Ishii, Taeko; Tanaka, Yoshiya.

In: Modern Rheumatology, 01.01.2019.

Research output: Contribution to journalArticle

Harigai, Masayoshi ; Takeuchi, Tsutomu ; Smolen, Josef S. ; Winthrop, Kevin ; Nishikawa, Atsushi ; Rooney, Terence P. ; Saifan, Chadi G. ; Issa, Maher ; Isaka, Yoshitaka ; Akashi, Naotsugu ; Ishii, Taeko ; Tanaka, Yoshiya. / Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment : An integrated analysis of Phases 2 and 3 trials. In: Modern Rheumatology. 2019.
@article{9db8c9871f8445519f0cc9414f5edbb7,
title = "Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: An integrated analysis of Phases 2 and 3 trials",
abstract = "Objectives: Baricitinib is a selective oral inhibitor of JAK1/JAK2 for patients with moderately-to-severely active rheumatoid arthritis (RA). Baricitinib’s safety profile in Japanese patients was evaluated using six studies (five Ph2/Ph3 trials, one long-term extension study through 01 September 2016) from an integrated database (nine RA studies). Methods: Incidence rates (IRs) or exposure-adjusted IRs (EAIRs) of adverse events (AEs) per 100 patient-years (PY) were calculated using data which included RA patients exposed to any baricitinib dose. Results: Five hundred and fourteen Japanese patients received baricitinib for 851.5 total PY of exposure (median 1.7 years, maximum 3.2). The EAIR of treatment-emergent AEs was 57.4/100PY. There were no deaths; 31 patients had serious infections (IR: 3.6/100PY), 55 herpes zoster (6.5), 0 tuberculosis, 10 malignancies (1.1) including two lymphomas, two major cardiovascular AEs (0.3), one gastrointestinal perforation (0.1), and four deep vein thrombosis (0.5). In Japanese patients, herpes zoster was more frequent than that of patients overall in the integrated database, but the events were considered manageable. Conclusion: In this analysis, baricitinib had acceptable safety profile in Japanese RA patients in the context of demonstrated efficacy. Aside from herpes zoster, baricitinib safety was not notably different between Japanese RA patients and those RA patients in the integrated database. Trial registration: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and NCT01885078 at https://clinicaltrials.gov/.",
keywords = "Baricitinib, Janus kinase (JAK), Japanese, rheumatoid arthritis, safety",
author = "Masayoshi Harigai and Tsutomu Takeuchi and Smolen, {Josef S.} and Kevin Winthrop and Atsushi Nishikawa and Rooney, {Terence P.} and Saifan, {Chadi G.} and Maher Issa and Yoshitaka Isaka and Naotsugu Akashi and Taeko Ishii and Yoshiya Tanaka",
year = "2019",
month = "1",
day = "1",
doi = "10.1080/14397595.2019.1583711",
language = "English (US)",
journal = "Modern Rheumatology",
issn = "1439-7595",
publisher = "Springer Japan",

}

TY - JOUR

T1 - Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment

T2 - An integrated analysis of Phases 2 and 3 trials

AU - Harigai, Masayoshi

AU - Takeuchi, Tsutomu

AU - Smolen, Josef S.

AU - Winthrop, Kevin

AU - Nishikawa, Atsushi

AU - Rooney, Terence P.

AU - Saifan, Chadi G.

AU - Issa, Maher

AU - Isaka, Yoshitaka

AU - Akashi, Naotsugu

AU - Ishii, Taeko

AU - Tanaka, Yoshiya

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: Baricitinib is a selective oral inhibitor of JAK1/JAK2 for patients with moderately-to-severely active rheumatoid arthritis (RA). Baricitinib’s safety profile in Japanese patients was evaluated using six studies (five Ph2/Ph3 trials, one long-term extension study through 01 September 2016) from an integrated database (nine RA studies). Methods: Incidence rates (IRs) or exposure-adjusted IRs (EAIRs) of adverse events (AEs) per 100 patient-years (PY) were calculated using data which included RA patients exposed to any baricitinib dose. Results: Five hundred and fourteen Japanese patients received baricitinib for 851.5 total PY of exposure (median 1.7 years, maximum 3.2). The EAIR of treatment-emergent AEs was 57.4/100PY. There were no deaths; 31 patients had serious infections (IR: 3.6/100PY), 55 herpes zoster (6.5), 0 tuberculosis, 10 malignancies (1.1) including two lymphomas, two major cardiovascular AEs (0.3), one gastrointestinal perforation (0.1), and four deep vein thrombosis (0.5). In Japanese patients, herpes zoster was more frequent than that of patients overall in the integrated database, but the events were considered manageable. Conclusion: In this analysis, baricitinib had acceptable safety profile in Japanese RA patients in the context of demonstrated efficacy. Aside from herpes zoster, baricitinib safety was not notably different between Japanese RA patients and those RA patients in the integrated database. Trial registration: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and NCT01885078 at https://clinicaltrials.gov/.

AB - Objectives: Baricitinib is a selective oral inhibitor of JAK1/JAK2 for patients with moderately-to-severely active rheumatoid arthritis (RA). Baricitinib’s safety profile in Japanese patients was evaluated using six studies (five Ph2/Ph3 trials, one long-term extension study through 01 September 2016) from an integrated database (nine RA studies). Methods: Incidence rates (IRs) or exposure-adjusted IRs (EAIRs) of adverse events (AEs) per 100 patient-years (PY) were calculated using data which included RA patients exposed to any baricitinib dose. Results: Five hundred and fourteen Japanese patients received baricitinib for 851.5 total PY of exposure (median 1.7 years, maximum 3.2). The EAIR of treatment-emergent AEs was 57.4/100PY. There were no deaths; 31 patients had serious infections (IR: 3.6/100PY), 55 herpes zoster (6.5), 0 tuberculosis, 10 malignancies (1.1) including two lymphomas, two major cardiovascular AEs (0.3), one gastrointestinal perforation (0.1), and four deep vein thrombosis (0.5). In Japanese patients, herpes zoster was more frequent than that of patients overall in the integrated database, but the events were considered manageable. Conclusion: In this analysis, baricitinib had acceptable safety profile in Japanese RA patients in the context of demonstrated efficacy. Aside from herpes zoster, baricitinib safety was not notably different between Japanese RA patients and those RA patients in the integrated database. Trial registration: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and NCT01885078 at https://clinicaltrials.gov/.

KW - Baricitinib

KW - Janus kinase (JAK)

KW - Japanese

KW - rheumatoid arthritis

KW - safety

UR - http://www.scopus.com/inward/record.url?scp=85063160012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063160012&partnerID=8YFLogxK

U2 - 10.1080/14397595.2019.1583711

DO - 10.1080/14397595.2019.1583711

M3 - Article

JO - Modern Rheumatology

JF - Modern Rheumatology

SN - 1439-7595

ER -