Publications

Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM

J Clin Med. 2019 Sep 5;8(9). pii: E1394

Fautrel B,

Kirkham B,

Pope JE,

Takeuchi T,

Gaich C,

Quebe A,

Zhu B,

de la Torre I,

De Leonardis F,

Taylor PC

Post hoc analyses from RA-BEAM concluded that BARI 4 mg QD or ADA 40 mg Q2W resulted in improvements in pain, physical function, fatigue and work productivity in patients with RA, independent of the treatment’s impact on inflammation. Among patients achieving remission or LDA, greater improvements in pain and physical function were seen with BARI than with ADA or PBO.Of 1010 patients included in the analysis at Week 24, 168 were in remission, 310 were in remission/LDA and 700 were not in remissi...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• Pain

Efficacy and Safety of Peficitinib (ASP015K) in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III Randomised, Double-Blind, Placebo-Controlled Trial (RAJ4) in Japan

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215164

Takeuchi T,

Tanaka Y,

Tanaka S,

Kawakami A,

Iwasaki M,

Katayama K,

Rokuda M,

Izutsu H,

Ushijima S,

Kaneko Y,

Shiomi T,

Yamada E,

van der Heijde D

Peficitinib (PEF) 100 and 150 mg demonstrated robust clinical and structural efficacy in patients with RA who have an inadequate response to MTX. In Japan, two JAK inhibitors, TOF and BARI are currently available for RA patients with an inadequate response to conventional therapies. This randomized phase 3 study (RAJ4), assessed the efficacy and safety of two PEF doses in combination with MTX compared to PBO, in Japanese MTX-IR. Patients were randomized 1:1:1 to PBO, PEF 100 mg and 150 mg with M...

Keywords:

• JAK,
• Peficitinib,
• Phase 3

Effect of Filgotinib vs Placebo on Clinical Response in Patients with Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial

JAMA 2019 322(4):315-325

Genovese MC,

Kalunian K,

Gottenberg JE,

Mozaffarian N,

Bartok B,

Matzkies F,

Gao J,

Guo Y,

Tasset C,

Sundy JS,

de Vlam K,

Walker D,

Takeuchi T

Among RA patients with an inadequate response or intolerance to bDMARDs, filgotinib (FIL) doses, compared to PBO resulted in significantly greater proportions achieving a clinical response at Wk12.Patients with active RA despite treatment with bDMARD therapy need treatment options. The FINCH 2 Phase 3 study compared the effects of FIL vs PBO for the treatment of RA patients with inadequate response or intolerance to ≥1 prior bDMARDs. Patients were randomized in a 1:1:1 ratio, receiving FIL 200 m...

Keywords:

• JAK,
• Filgotinib,
• Phase 3

Safety Profile of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis with Over 1.6 Years Median Time in Treatment: An Integrated Analysis of Phase 2 and 3 Trials

Mod Rheumatol. 2019 Feb 20:1-23. DOI: 10.1080/14397595.2019.1583711

Harigai M,

Takeuchi T,

Smolen JS,

Winthrop KL,

Nishikawa A,

Rooney TP,

Saifan CG,

Issa M,

Isaka Y,

Akashi N,

Ishii T,

Tanaka Y

In this integrated analysis, BARI showed an acceptable safety profile in Japanese patients with up to 3.2 years of exposure. Other than incidences of herpes zoster (HZ), no major differences were noted with BARI safety in Japanese patients with RA, compared to the patients in the integrated database.BARI has previously demonstrated significant clinical efficacy and acceptable safety. Japanese patients who participated in the BARI clinical development programme, were comparable to those from the ...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Phase 3

Cardiovascular Safety During Treatment with Baricitinib in Rheumatoid Arthritis

Arthritis Rheumatol. 2019 Jul;71(7):1042-1055.

Taylor PC,

Weinblatt ME,

Burmester GR,

Rooney TP,

Witt S,

Walls CD,

Issa M,

Salinas CA,

Saifan C,

Zhang X,

Cardoso A,

González-Gay MA,

Takeuchi T

This study indicates no association between exposure to BARI and MACE, arterial thrombotic events (ATE), or congestive heart failure (CHF). Overall IRs for venous thromboembolic event (VTE) in BARI-treated patients falls within the reported range for patients with RA.RA patients have a greater risk of cardiovascular (CV) diseases of arterial ischemic origin, and an increased risk of VTE. Studied frequencies of thromboembolic events in RA populations in the last decade has been reported as 2–3x h...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Cardiovascular

Professor Iain McInnes Reviews the Most Notable Papers from 2018

Please click the links below to go to the CSF review of each paper

McInnes. I

2018 brought a wealth of new data in cytokine signalling and IL-6 that helps inform current clinical practice and brings the promise of new options in the future. There was good data on the use of sub cutaneous tocilizumab as well as strategies in early RA and for methotrexate tapering. For the currently marketed JAK inhibitors, tofacitinib and baricitinib, continuous long-term efficacy and safety data further support its current use and applications. On the development side, the outcomes of the...

Keywords:

• Review

Dose Reduction of Baricitinib in Patients with Rheumatoid Arthritis Achieving Sustained Disease Control: Results of a Prospective Study

Ann Rheum Dis. 2019 Feb;78(2):171-178. DOI 10.1136/annrheumdis-2018-213271

Takeuchi T,

Genovese MC,

Haraoui B,

Li Z,

Xie L,

Klar R,

Pinto Correia A,

Otawa S,

Lopez-Romero P,

de la Torre I,

Rooney TP,

Smolen JS

In active RA patients, with an inadequate response (IR) to DMARDs who achieve low disease activity (LDA) following baricitinib (BARI) 4 mg treatment, disease control is better maintained with continued BARI 4 mg compared to tapering to 2 mg.The objective of this study was to investigate the effect of BARI tapering in patients achieving sustained disease control with BARI 4 mg.In the long-term extension study RA-BEYOND, patients receiving BARI 4 mg who achieved sustained LDA or remission at two c...

Keywords:

• JAK,
• Baricitinib

Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment

J Rheumatol. 2019 Jan;46(1):7-18. DOI: 10.3899/jrheum.171361

Smolen J,

Genovese M,

Takeuchi T,

Hyslop D,

Macias W,

Rooney T,

Chen L,

Dickson C,

Riddle Camp J,

Cardillo T,

Ishii T and Winthrop K

Baricitinib (BARI) showed an acceptable 5.5-year safety profile in this integrated analysis of patients with moderate-to-severe, active RA.This study evaluated the safety profile of the oral, once daily Janus kinase inhibitor, BARI, in adults with moderately to severely active RA. Data from eight randomised clinical trials and one long-term extension study were pooled and analysed for placebo comparison and dose response.There were 3492 patients who received BARI for a total of 6637 patient-yea...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Review

Tocilizumab Discontinuation After Attaining Remission in Patients with Rheumatoid Arthritis who were Treated with Tocilizumab Alone or in Combination with Methotrexate: Results from a Prospective Randomised Controlled Study (the second year of the SURPRISE study)

Ann Rheum Dis 2018; 77:1268–1275 DOI: 10.1093/rheumatology/key121

Kaneko Y,

Kato M,

Tanaka Y,

Inoo M,

Kobayashi-Haraoka H,

Amano K,

Miyata M,

Murakawa Y,

Yasuoka H,

Hirata S,

Tanaka E,

Miyasaka N,

Yamanaka H,

Yamamoto K,

Takeuchi T,

the SURPRISE study group

The second-year results from the SURPRISE study show that low disease activity (LDA) can be maintained after discontinuation of tocilizumab with continued methotrexate after remission is achieved. Discontinuation of biologic agents in patients who have achieved remission or low disease activity (LDA) is desirable from a risk–benefit point of view. Compared with TNF inhibitors, little is known regarding TCZ-free remission or LDA, but studies indicate that only a small proportion of patients remai...

Keywords:

• IL-12,
• Tocilizumab,
• Phase 3,
• Persistence

Patient-reported Outcomes of Baricitinib in Patients with Rheumatoid Arthritis and No or Limited Prior Disease-modifying Antirheumatic Drug Treatment

Arthritis Res Ther. 2017 Sep 18;19(1):208

Schiff M,

Takeuchi T,

Fleischmann R,

Gaich CL,

DeLozier AM,

Schlichting D,

Kuo W,

Won J,

Carmack T,

Rooney T,

Durez P,

Shaikh S,

Hidalgo RP,

van Vollenhoven R,

Zerbini C

RA-BEGIN was a Phase 3, double-blind randomised active comparator-controlled study to evaluate baricitinib as monotherapy or in combination with MTX in patients with active RA who were naïve to csDMARDS and bDMARDS. In this analysis of the RA-BEGIN study, baricitinib alone or with MTX when used as initial therapy resulted in significant improvements in most patient-reported outcome measures compared with MTX. At baseline, study participants had active RA, impaired physical function, moderate le...

Keywords:

• JAK,
• Baricitinib,
• PRO / QoL