Comparaison du Baricitinib, Upadacitinib et Tofacitinib médié par la régulation de la signalisation des cytokines dans les sous-populations de leucocytes humains

Arthritis Res Ther. 2019 Aug 2;21(1):183

McInnes IB,

Byers NL,

Higgs RE,

Lee J,

Macias WL,

Na S,

Ortmann RA,

Rocha G,

Rooney TP,

Wehrman T,

Zhang X,

Zuckerman SH,

Taylor PC

Different JAKinibs modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signalling pathway throughout the dosing interval. This study aimed to compare the in vitro cellular pharmacology of BARI, TOF and UPA across relevant leukocyte subpopulations, coupled with their in vivo PK, to determine their effects on distinct cytokine pathways. Peripheral blood mononuclear cells from healthy donors were incubated with different JA...

Keywords:

• JAK,
• Baricitinib,
• Tofacitinib,
• Upadacitinib,
• MOA

Caractérisation et Modifications des Sous-Types de Lymphocytes chez les patients traités au Baricitinib avec une Polyarthrite Rhumatoïde: Une Analyse Intégrée

Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680

Tanaka Y,

McInnes IB,

Taylor PC,

Byers NL,

Chen L,

de Bono S,

Issa M,

Macias WL,

Rogai V,

Rooney TP,

Schlichting DE,

Zuckerman SH,

Emery P

This review shows that changes in lymphocyte subsets were largely within normal reference ranges and were not associated with efficacy or safety end points. BARI is a selective JAK1/JAK2 inhibitor, approved for the treatment of moderate to severe RA. BARI treatment is associated with changes to circulating lymphocyte and lymphocyte subsets, however detailed analyses of these effects, and their relevance to efficacy and safety is lacking. This study investigated the changes in lymphocyte cell sub...

Keywords:

• JAK,
• Baricitinib,
• Basic Science,
• MOA

Profil d'innocuité du Baricitinib chez les patients atteints de polyarthrite rhumatoïde active, traités plus de 2 ans en moyenne

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

Profil Lipidique et Effet du Traitement aux Statines dans des Études Groupées de Phase II et Phase III sur le Baricitinib

Ann Rheum Dis. 2018 Jul;77(7):988-995. DOI 10.1136/annrheumdis-2017-212461

Taylor PC,

Kremer JM,

Emery P,

Zuckerman SH,

Ruotolo G,

Zhong J,

Chen L,

Witt S,

Saifan C,

Kurzawa M,

Otvos JD,

Connelly MA,

Macias WL,

Schlichting DE,

Rooney TP,

de Bono S,

McInnes IB

Baricitinib (BARI) was associated with increased lipid levels; baseline statins did not alter these profiles. The introduction of statins during treatment reduced total cholesterol and LDL-C.The use of anti-inflammatory drugs in RA patients has been shown to alter lipid levels and is associated with reduced atherogenic risk. Increases in lipid levels, specifically HDL-C and LDL-C, have been observed in Phase 2 BARI studies1.This study analysed data from seven randomised RA Phase 2/3 studies of ...

Keywords:

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

Réponse à Baricitinib Basée sur l’Utilisation de Traitements Biologiques Antérieurs chez les Patients avec une Arthrite Réfractaire

Rheumatology (Oxford) 2018 May; 57(5):900-908

Genovese MC,

Kremer JM,

Kartman CE,

Schlichting DE,

Xie L,

Carmack T,

Pantojas C,

Burston JS,

Tony HP,

Macias WL,

Rooney TP,

Smolen JS

Baricitinib (BARI) 2 or 4 mg had a beneficial treatment effect on patients with moderate to severe RA compared with placebo (PBO), irrespective of the number or nature of prior patient bDMARD use. The current therapeutic target for patients with established RA is low disease activity, but many patients fail to achieve this due to inadequate responses to DMARD therapies. With this patient population growing, therapies for these patients are considered one of the greatest unmet needs in RA. This s...

Keywords:

• JAK,
• Baricitinib

Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase 2b Study in Patients with Active Rheumatoid Arthritis

Arthritis Rheumatol 2017. DOI 10.1002/art.40036.

Kremer J,

Genovese MC,

Keystone E,

Taylor PC,

Zuckerman SH,

Ruotolo G,

Schlichting DE,

Crotzer VL,

Nantz E,

Beattie SD and Macias WL

In this analysis of the effect of baricitinib on changes in lipid profile, lipoprotein particle size and apolipoprotein content, increases in serum lipids were observed with HDL-C increases correlating with improved clinical outcomes.Eligible patients (N=301) met the inclusion criteria for the Phase 2b randomised, double-blind, placebo-controlled study.1 Patients were assigned in a 2:1:1:1:1 ratio to once-daily doses of placebo or baricitinib 1, 2, 4, or 8 mg, respectively. Those receiving 2 mg,...

Keywords:

• JAK,
• Baricitinib,
• Phase 2

Baricitinib, Methotrexate, or Combination in Patients with Rheumatoid Arthritis and no or Limited Prior Disease-Modifying Antirheumatic Drug Treatment

Arthritis Rheumatol 2016. DOI 10.1002/art.39953. Accepted article

Fleischmann F,

Schiff M,

van der Heijde D,

Ramos-Remus C,

Spindler A,

Stanislav M,

Zerbini CAF,

Gurbuz S,

Dickson C,

de Bono S,

Schlichting D,

Beattie S,

Kuo W-L,

Rooney T,

Macias W,

Takeuchi T

In this 52-week study of patients receiving initial therapy for RA, baricitinib alone or in combination with MTX demonstrated superior efficacy compared with MTX alone.Patients naïve to csDMARD (no or <3 doses of MTX) or bDMARD were randomised 4:3:4 (N=588) toMTX QW, baricitinib 4 mg QD or baricitinib 4 mg QD + MTX QW. The primary endpoint assessment was noninferiority of baricitinib monotherapy to MTX based on ACR20 response at Week 24.Not only was the primary endpoint met, baricitinib monother...

Keywords:

• JAK,
• Baricitinib,
• Phase 3

Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate

Ann Rheum Dis. 2015;74(2):333–340

Keystone EC,

Taylor PC,

Drescher E,

Schlichting DE,

Beattie SD,

Berclaz PY,

Lee CH,

Fidelus-Gort RK,

Luchi ME,

Rooney TP,

Macias WL,

Genovese MC.

Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies.

This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitin...

Keywords:

• JAK,
• Baricitinib,
• Phase 2