Publications

Filgotinib, a Novel JAK1-Preferential Inhibitor for the Treatment of Rheumatoid Arthritis: An Overview from Clinical Trials

Mod Rheumatol. 2021 Mar 19:1-26. Epub ahead of print. DOI 10.1080/14397595.2021.1902617

Tanaka Y,

Kavanaugh A,

Wicklund J,

McInnes IB

Filgotinib is the latest JAKinib to enter the international market for the treatment of RA, receiving regulatory approval in Japan and Europe late last year. In this review paper, Tanaka Y et al. examine the clinical evidence supporting its use as a later-line treatment, in accordance with international RA management guidelines, and provide their expert opinions on JAKinibs from a clinical perspective.The core clinical programme evaluating filgotinib in patients with moderately-to-severely activ...

Keywords:

• JAK,
• Fenebrutinib,
• Review

Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program

Drug Saf. 2021 Feb 2. DOI: 10.1007/s40264-020-01036-w

Conaghan PG,

Mysler E,

Tanaka Y,

Da Silva-Tillmann B,

Shaw T,

Liu J,

Ferguson R,

Enejosa JV,

Cohen S,

Nash P,

Rigby W,

Burmester G

Upadacitinib 15 mg has a favourable benefit–risk profile according to an assessment of data from the phase III SELECT clinical trial programme.In this review of data for the once-daily, oral JAK inhibitor, Conaghan PG, et al. provided insights into the benefit–risk profile of upadacitinib in approximately 4400 patients with RA. Based on pooled data from five pivotal studies, benefits and risks were assessed up to the time of regulatory submission, and additional long-term integrated safety revie...

Keywords:

• JAK,
• Updacitinib,
• Phase 3,
• Review

Baricitinib Inhibits Structural Joint Damage Progression in Patients with Rheumatoid Arthritis – A Comprehensive Review

Arthritis Res Ther 2021;23(1):3.

Emery P,

Durez P,

Hueber AJ,

Ide la Torre I,

Larsson E,

Holzkämper T,

Tanaka Y

MRI studies have shown that BARI reduces joint inflammation and damage in patients with moderate-to-severe active RA. This review summarises the effects of BARI on structural joint damage progression and the mechanisms underlying these effects, using MRI data from across the clinical trial program. Early preclinical animal models showed a significant reduction in joint inflammation, ankle width, and bone resorption. Efficacy and safety of BARI have been confirmed in an extensive programme, inclu...

Keywords:

• JAK,
• Baricitinib,
• Radiographic,
• Review

Filgotinib Versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and Inadequate Response to Methotrexate: A Phase III Randomised Clinical Trial

Ann Rheum Dis. 2021 Jan 27:annrheumdis-2020-219214

Combe B,

Kivitz A,

Tanaka Y,

van der Heijde D,

Simon JA,

Baraf HSB,

Kumar U,

Matzkies F,

Bartok B,

Ye L,

Guo Y,

Tasset C,

Sundy JS,

Jahreis A,

Genovese MC,

Mozaffarian M,

Landewé RBM,

Bae S-C,

Keystone EC,

Nash P

Filgotinib improved RA signs and symptoms, physical function, and inhibited radiographic progression. FIL 200mg plus MTX, but not FIL 100mg plus MTX showed non-inferiority to ADA plus MTX, based on DAS28(CRP) low disease activity. FIL was also well tolerated in RA patients with inadequate response to MTX.This 52-week, phase 3 randomised clinical trial (FINCH 1) evaluated the efficacy and safety of FIL in patients with RA randomised to FIL 200 or 100mg, ADA 40mg, or placebo, all with background M...

Keywords:

• JAK,
• Fenebrutinib,
• Phase 3

Efficacy of baricitinib in patients with moderate-to-severe rheumatoid arthritis with 3 years of treatment: results from a long-term study

Rheumatology 2020; doi:10.1093/rheumatology/keaa576

Smolen JS,

Xie L,

Jia B,

Taylor PC,

Burmester G,

Tanaka Y,

Elias A,

Cardoso A,

Ortmann R,

Walls C,

Dougados M

Three year follow up data for baricitinib demonstrated efficacy in populations that span the clinical disease continuum in RA, including DMARD-naïve, MTX-IR, csDMARD-IR, and bDMARD-IR and was well tolerated. This study evaluated achievement and maintenance of LDA, remission and physical functioning in patients treated with baricitinib for up to 3 years. Data were analysed from two 52-week, Phase 3 studies (RA-BEAM and RA-BEGIN), and one ongoing long-term extension (RA-BEYOND). Patients completin...

Keywords:

• JAK,
• Baricitinib,
• LTE,
• Efficacy

Safety Profile of Upadacitinib in Rheumatoid Arthritis: Integrated Analysis from the SELECT Phase III Clinical Programme

Ann Rheum Dis 2020 DOI:10.1136/annrheumdis-2020-218510

Cohen SB,

van Vollenhoven RF,

Winthrop KL,

Zerbini CAF,

Tanaka Y,

Bessette L,

Zhang Y,

Khan N,

Hendrickson B,

Enejosa JV,

Burmester GR.

This integrated Phase III safety analysis of UPA showed that UPA had a similar profile to ADA and MTX for serious infections, malignancies, and thromboembolic events. Patients receiving UPA had increased risk of HZ and creatine phosphokinase elevation versus ADA.This integrated Phase III safety analysis of UPA examined >3500 RA patients and 4000 patient-years of exposure. Data were pooled from 3834 patients in SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY studie...

Keywords:

• JAK,
• Updacitinib,
• Safety,
• Phase 3

Temporary Interruption of Baricitinib: Characterization of Interruptions and Effect on Clinical Outcomes in Patients With Rheumatoid Arthritis

Arth Res Ther 2020;22:115 doi.org/10.1186/s13075-020-02199-8

Emery P,

Tanaka Y,

Cardillo T,

Schlichting D,

Rooney T,

Beattie S,

Helt C,

Smolen JS

This study aimed to characterize temporary interruptions of baricitinib and describe their impact on efficacy and safety. Brief interruptions during phase 3 baricitinib trials were associated with minor increases in symptoms which were resolved following treatment. In life-long, chronic conditions such as RA, interruption of therapy is common for various reasons, such as side effects, non-compliance, or because a patient requires surgery. Concerns have been raised that these treatment breaks cou...

Keywords:

• JAK,
• Baricitinib,
• Efficacy

Tofacitinib in Combination with Methotrexate in Patients with Rheumatoid Arthritis: Patient-reported Outcomes from the 24-month Phase 3 ORAL Scan study

Clin Exp Rheumatol . Sep-Oct 2020;38(5):848-857. Epub 2019 Dec 19.

Strand V,

van der Heijde D,

Tanaka Y,

Keystone E,

Kremer J,

Zerbini C A F,

Cardiel M H,

Cohen S,

Nash P,

Song Y-W,

Tegzová D,

Gruben D,

Wallenstein G,

Connell C A,

Fleischmann R

In the ORAL SCAN study, patients receiving TOF 5 mg or 10 mg BID reported significant improvements in patient-reported outcomes at month 3 compared with placebo, which were maintained through 24 months of treatment.RA causes a significant health and socioeconomic burden and affects all aspects of health related quality of life. ORAL Scan included patients with active RA and inadequate response to MTX who were randomised to receive TOF 5 mg or 10 mg BID plus MTX or PBO. This study evaluated the i...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• PRO / QoL

Highlights of 2019

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

McInnes. I

2019 was another remarkable year in cytokine signalling. We can be optimistic that clinical practice for inflammatory arthritis will continue to improve, with promising long-term safety data supporting the use of established JAK inhibitors; tofacitinib and baricitinib, in addition to exciting phase III clinical data for filgotinib and newly approved upadacitinib. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respecti...

Keywords:

• Review

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