Publications

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

Points À Considérer Pour le Traitement des Maladies Inflammatoires Immunitaires par les Inhibiteurs de Janus Kinase : une Recherche Bibliographique Systématique

RMD Open 2020;6:e001374 doi:10.1136/rmdopen-2020-001374

Kerschbaumer A,

Smolen JS,

Nash P,

Doerner T,

Dougados M,

Fleischmann R,

Geissler K,

McInnes IM,

Takeuchi T,

Trauner M,

Winthrop K,

de Wit M,

Boehncke W-H,

Falzon L,

van der Heijde D

Trials of JAKi have been conducted in many therapy areas, including rheumatology, dermatology and gastroenterology. In 2019, a task force was set up to create a consensus to guide clinicians on how to use JAKi in clinical practice. This systematic literature review conducted in 2019 support this consensusIn line with EULAR’s standardised operating procedures for recommendations, a literature search was conducted in EMBASE, Medline and the Cochrane Library databases. To evaluate the efficacy of t...

Keywords:

• JAK,
• Review

Passage de l'Upadacitinib, un Inhibiteur de Janus Kinase, à l'Adalimumab Suite à une Réponse Insuffisante : Efficacité et Innocuité Chez les Patients Atteints de Polyarthrite Rhumatoïde

Ann Rheum Dis 2020; doi:10.1136/annrheumdis-2020-21841220

Fleischmann RM,

Blanco R,

Hall S,

Thomson GTD,

Van den Bosch FE,

Zerbini C,

Bessette L,

Enejosa J,

Li Y,

Song Y,

DeMasi R,

Song I-H

Both ACR and EULAR recommend adding a biologic or targeted synthetic DMARD in patients who do not achieve treatment goals at follow-up. Findings indicated that an immediate switch in mechanism of action (from JAKi to TNFi and vice versa) following treat-to-target principles is feasible with minimal risk of flare regardless of whether patients are switched due to non-response or incomplete-response.SELECT-COMPARE followed treat-to-target principles to examine the efficacy of switching in two pati...

Keywords:

• JAK,
• TNF,
• Upadacitinib,
• Adherence,
• Switching

Profil d'Innocuité de l'Upadacitinib Dans la Polyarthrite Rhumatoïde : Analyse Intégrée du Programme Clinique de Phase III SELECT

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,
• Upadacitinib,
• Safety,
• Phase 3

Caractérisation Préclinique de l'Itacitinib (INCB039110), un Nouvel Inhibiteur Sélectif de JAK1, Pour le Traitement des Maladies Inflammatoires

European Journal of Pharmacology. 2020 Oct 15;885:173505. doi: 10.1016/j.ejphar.2020.173505

Covington M,

He X,

Scuron M,

Li J,

Collins R,

Juvekar A,

Shin N,

Favata M,

Gallagher K,

Sarah S,

Xue CB,

Peel M,

Burke K,

Oliver J,

Fay B,

Yao W,

Huang T,

Scherle P,

Diamond S,

Newton R,

Zhang Y,

Smith

Itacitinib is an orally active JAK inhibitor and effectively delayed disease onset, reduced symptom severity, and accelerated recovery of inflammatory diseases in mouse models. Covington M et al demonstrated itacitinib’s high selectivity for JAK 1, its inhibition on IL-2 induced T cell proliferation and JAK/STAT signalling, its ability to also inhibit of the JAK/STAT pathway in response to IL-6 stimulation, and its effect on rat adjuvant induced arthritis model. The study used recombinant enzym...

Keywords:

• JAK,
• Itacitinib

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

Efficacité et Innocuité de l’Upadacitinib en Monothérapie Chez les Patients Méthotrexate-Naïfs Avec une Polyarthrite Rhumatoïde Modérément À Sévèrement Active (Select-early) : Un Essai Randomisé, en Double Aveugle, À Comparateur Actif, Multicentrique et Multinational

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,
• Upadacitinib,
• Phase 3

COVID-19 : Revisiter les Voies Inflammatoires de l'Arthrite

Nat Rev Rheumatol 2020 doi.org/10.1038/s41584-020-0451-z

Schett G,

Manger B,

Simon D,

Caporali R

This review investigates the potential implications of COVID-19 on the field of rheumatology. Common pathways in COVID-19 and RA have provided rationale for the trial of DMARD therapies in treatment of severe COVID-19 infections. Safety considerations of RA patients undergoing immunomodulatory treatments are reviewed. Recommendations suggest that RA patients should continue DMARD treatment, whereas glucocorticoid use could be deleterious in COVID-19 infection and should be considered carefully, ...

Fénébrutinib Versus Placebo ou Adalimumab Dans la Polyarthrite Rhumatoïde : un Essai de Phase II Randomisé, en Double Aveugle (Étude ANDES)

Arthritis Rheumatol. 2020 Sep; 72(9): 1435–1446.

Cohen S,

Tuckwell K,

Katsumoto TR,

Zhao R,

Galanter J,

Lee C,

Rae J,

Toth B,

Ramamoorthi N,

Hackney JA,

Berman A,

Damjanov N,

Fedkov D,

Jeka S,

Chinn LW,

Townsend MJ,

Morimoto AM,

Genovese MC

In this randomised phase II trial with MTX treatment-refractory RA patients, greater efficacy was observed with fenebrutinib 150 mg once daily or 200 mg twice daily compared to placebo, while response rates were numerically similar to those observed with adalimumab. BTK inhibitors have demonstrated clinical efficacy in B cell malignancies and multiple sclerosis, although there is limited clinical evidence of its efficacy in RA. Fenebrutinib (FEN) an orally active and selective non-covalent inhib...

Keywords:

• BTK,
• Fenebrutinib,
• Phase 2

L'Ostéo-Immunologie Dans La Polyarthrite Rhumatoïde Et Psoriasique : Effets Potentiels Du Tofacitinib Sur I‘Atteinte Osseuse

Clin Rheumatol. 2020

Orsolini G,

Bertoldi I,

Rossini M.

Data showing that TOF can inhibit unbalanced osteoclastogenesis in RA suggests that targeting the JAK-STAT pathway can halt bone erosion, as TOF has been shown to reduce articular bone erosion in RA and PsA.The authors in this review summarise current knowledge on the relationship between the immune system and the skeleton before examining the involvement of JAK-STAT signalling in bone homeostasis while discussing the evidence on the benefit of TOF on prevention of bone involvement in RA and PsA...

Keywords:

• JAK,
• Tofacitinib,
• Basic Science