Cytokine Signalling Forum

Publications





January 22

Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment

Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR.
Rheumatol Ther. 2021. Epub ahead of print. doi: 10.1007/s40744-021-00390-0

This post hoc analysis provides the first detailed description of the management and outcomes of HZ events in tofacitinib RA and PsA clinical studies. While prior studies have characterised the increased HZ risk with JAKinibs, the clinical management of these events has not been detailed. To this end, Winthrop, et al. analysed data from 21 RA and 3 PsA clinical studies to evaluate how HZ events and their sequelae were clinically managed during the RA and PsA tofacitinib clinical development pr...

November 21

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

Winthrop KL, Nash P, Yamaoka K, Mysler E, Khan N, Camp HS, Song Y, Suboticki JL, Curtis JR.
Ann Rheum Dis. 2021. Epub ahead of print. doi: 10.1136/annrheumdis-2021-220822.

JAKinibs have been linked with an increased risk of HZ in patients with RA. To this end, Winthrop, et al. evaluated data from six Phase III clinical trials to determine the incidence of HZ in the upadacitinib (UPA)-treated patients with RA and identify potential risk factors for the development of HZ in these patients. Analysis of data provides further support for the need for continued vigilance and monitoring for signs of herpes zoster (HZ) in patients receiving UPA, particularly in Asian popu...

November 17

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

Winthrop KL, Curtis JR, Lindsey S, Tanaka Y, Yamaoka K, Valdez H, Hirose T, Nduaka CI, Wang L, Mendelsohn AM, Fan H, Chen C, Bananis E.
Arthritis Rheumatol 2017;69(10):1960–68

The results of this analysis of patients with herpes zoster (HZ) within the global tofacitinib (TOF) RA programme suggest that there is likely to be a greater HZ risk in patients receiving TOF and glucocorticoids compared with patients receiving TOF monotherapy. The global TOF RA development programme comprised 2 Phase 1, 9 Phase 2, 6 Phase 3 and 2 long-term extension studies. These studies included 6192 patients; data were reviewed to identify cases of HZ. Crude incidence rates of number of pa...

May 17

Discontinuation of Tofacitinib after achieving Low Disease Activity in Patients with Rheumatoid Arthritis: a Multicentere, Observational Study

Kubo S, Yamaoka K, Amano K, Nagano S, Tohma S, Suematsu E, Nagasawa H, Iwata K and Tanaka Y.
Rheumatology. Doi 10.1093/rheumatology/kex068

This study showed that in patients who achieved low disease activity (LDA), it is possible to discontinue tofacitinib without flare in approximately one-third of patients. Patients from the tofacitinib Phase 3 programme and long-term extension study were enroled. Discontinuation was based on physician-patient decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib free at post-treatment Week 52. Of 64 patients treated with tofacitin...

February 14

Effects of tofacitinib on lymphocytes in rheumatoid arthritis: relation to efficacy and infectious adverse events

Sonomoto K, Yamaoka K, Kubo S et al.
Rheumatology doi:10.1093/rheumatology/ket466

Due to its function as a JAK1/3 inhibitor, tofacitinib has effects on a wide ranging variety of cells. The authors of this paper have previously reported a suppression in cytokine production by CD4+ T lymphocytes caused by tofacitinib, while others have reported reduced chemokine production from fibroblast-like synoviocytes. The effects of tofacitinib on other cells however remain largely unknown. This study focused on tofacitinib’s effects on CD4+ T lymphocyte proliferation and on subsets...

October 13

The JAK inhibitor, tofacitinib, reduces the t cell stimulatory capacity of human monocyte-derived dendritic cells

Kubo S, Yamaoka K, Kondo M, et al.
Ann Rheum Dis 2013. doi: 10.1136/annrheumdis-2013-203756

The role of JAKs is highly important in lymphocyte differentiation, but their function in dendritic cells in unknown. In this study, the authors used tofacitinib, a JAK inhibitor, to assess the function of these kinases in dendritic cell activity. The results show that tofacitinib reduced the expression of CD80/CD86 by suppressing the activation of interferon regulatory factor (IRF)-7 and production of type 1 interferon (IFN), and also decreased T cell stimulatory capability. This suggests a nov...