Publications

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

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

Annals of the rheumatic diseases. 2021 Mar 1;80(3):312-20.

Mease PJ,

Lertratanakul A,

Anderson JK,

Papp K,

Van den Bosch F,

Tsuji S,

Dokoupilova E,

Keiserman M,

Wang X,

Zhong S,

McCaskill RM,

Zueger P,

Pangan AL,

Tillett W

In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA. Despite the availability of bDMARDs in PsA, only a small proportion of patients achieve the recommended target of minimal disease activity; as such, additional treatment options are needed. Upadacitinib is under evaluation for PsA. This paper reports the 24-week data ...

Keywords:

• JAK,
• Updacitinib,
• Phase 3

Tofacitinib in psoriatic arthritis patients: skin signs and symptoms and health-related quality of life from two randomized Phase 3 studies

J Eur Acad Dermatol Venereol 2020;34:2809–2820.

Merola JF,

Papp KA,

Nash P,

Gratacós J,

Boehncke W-H,

Thaçi D,

Graham D,

Hsu M-A,

Wang C,

Wu J,

Young P

Considering the multi-domain nature of PsA, effective treatments must demonstrate efficacy across a range of clinical and patient-reported outcomes. Dermatologic symptoms often precede rheumatic manifestations in people with PsA, typically by 10 years. Tofacitinib demonstrated significant improvements across a range of outcomes including burdensome dermatologic symptoms. This post hoc analysis included data from two double-blind, Phase 3 studies in patients with active PsA and an inadequate resp...

Keywords:

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

Highlights of 2020

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

McInnes. I

2020 unfolded apace, dominated by COVID-19 - we have all had to adapt in our practice and in our knowledge base. Amid this there have continued to be a constant flow of publications and science in cytokine signaling, and as in previous years as we come the end of 2020, I will highlight some of the notable papers of the year. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respective detailed summaries below:

Keywords:

• Review

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

Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data

Annals of the Rheumatic Diseases 05 August 2020 2020 Nov;79(11):1400-1413. doi: 10.1136/annrheumdis-2019-216761. Epub 2020 Aug 5.

Mease P,

Charles-Schoeman C,

Cohen S,

Fallon L,

Woolcott J,

Yun H,

Kremer J,

Greenberg J,

Malley W,

Onofrei A,

Kanik KS,

Graham D,

Wang C,

Connell C,

Valdez H,

Hauben M,

Hung E,

Madsen A,

Jones TV,

Curtis JR

Concerns surrounding increased rates of PE and cardiovascular associated deaths has led to black box warnings when prescribing JAK inhibitors. As such, ongoing investigations regarding cardiovascular and VTE event risks in JAK inhibitor therapies, both clinical and real-world, are vital. Mease and colleagues consider data from clinical tofacitinib development programmes, and the ongoing real-data study A3921133. Conclusions from data analysis state that those with pre-existing cardiovascular and...

Keywords:

• JAK,
• Tofacitinib,
• Safety

Infections in Baricitinib Clinical Trials for Patients with Active Rheumatoid Arthritis

Annals of the Rheumatic Diseases, May 2020

Winthrop KL,

Harigai M,

Genovese MC,

Lindsey S,

Takeuchi T,

Fleischmann R,

Bradley JD,

Byers NL,

Hyslop DL,

Issa M,

Nishikawa A,

Rooney TP,

Witt S,

Dickson CL,

Smolen JS,

Dougados M

Baricitinib, an oral selective JAK1 and JAK2 inhibitor,8 demonstrated significant clinical efficacy in phase 3 RA trials. Pooled data from these trials, including a long-term extension (LTE), inform the safety profile for baricitinib, mainly to evaluate the incidence of infection in patients with active rheumatoid arthritis (RA), with a focus on serious infection, tuberculosis (TB), herpes zoster (HZ) and opportunistic infection (OI). The data collected were from eight double-blind randomised tr...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Infections

Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-naïve Patients with Moderately to Severely Active Rheumatoid Arthritis (SELECT-EARLY): A Randomized, Double-blind, Active-comparator, Multi-center, Multi-country Trial

Arthritis Rheumatol 2020

van Vollenhoven R,

Takeuchi T,

Pangan AL,

Friedman A,

Mohamed MEF,

Chen S,

Rischmueller M,

Blanco R,

Xavier RM,

Strand V

Upadacitinib monotherapy demonstrated superior clinical, radiographic, and patient-reported outcomes versus methotrexate in methotrexate-naïve RA patients.This 48-week double-blind active comparator study investigated upadacitinib monotherapy in patients with early RA, who were either methotrexate-naïve, or who had very limited exposure. 947 patients were randomised to once-daily upadacitinib 15 or 30 mg, or weekly methotrexate. Unusually, there were two separate primary endpoints, selected for ...

Keywords:

• JAK,
• Updacitinib,
• 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