Cytokine Signalling Forum

Publications





February 19

Cardiovascular Safety During Treatment with Baricitinib in Rheumatoid Arthritis

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.
Arthritis Rheumatol 2019 DOI: 10. 1002/art.40841

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&nd...

Keywords: JAK, Baricitinib, Clinical, Safety

January 19

Characterization and Changes of Lymphocyte Subsets in Baricitinib-Treated Patients With Rheumatoid Arthritis: An Integrated Analysis.

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

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 s...

Keywords: JAK, Baricitinib, Clinical, Safety

November 18

Safety and Efficacy of Baricitinib in Patients Receiving Conventional Synthetic Disease-Modifying Antirheumatic Drugs or Corticosteroids

van Vollenhoven R, Helt C, Arora V, Zhong J, Correia AP, de la Torre I, Muram D.
Rheumatol Ther 2018 Dec;5(2):525-536. DOI 10.1007/s40744-018-0128-0

Baricitinib (BARI) in combination with MTX and concomitant csDMARDs was shown to be efficacious, regardless of corticosteroid use in RA patients. MTX is prescribed to most RA patients but concomitant csDMARDs and/or corticosteroids can be added. This study assessed the efficacy and safety of BARI in two arms; with/without corticosteroids and; with MTX only/MTX plus csDMARD/csDMARDs only. Baseline characteristics and adverse reactions were also compared. Data were pooled from two phase 3 studie...

Keywords: JAK, Baricitinib, Clinical, Phase 3

October 18

A Network Meta-Analysis Comparing Efficacy and Safety of Tofacitinib and Baricitinib

Bae SC and Lee YH.
Z Rheumatol. 2018 Sep 6. DOI 10.1007/s00393-018-0531-5

Tofacitinib (TOF) 10mg and baricitinib (BARI) 4mg, in combination with methotrexate (MTX), were the most efficacious treatments in RA patients with an inadequate response to DMARDs or biologics. Both combination treatments presented acceptable safety profiles and were not associated with a significant risk of serious adverse events. This study employed a Bayesian approach to Meta-Analysis; combining the available evidence across a network of Randomised Controlled trials (RCTs). Twelve RCTs cont...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

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

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

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...

Keywords: JAK, Baricitinib, Clinical, Phase 3

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

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

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-y...

Keywords: JAK, Baricitinib, Clinical, Phase 3

September 18

Structural Damage Progression in Patients with Early Rheumatoid Arthritis Treated with Methotrexate, Baricitinib, or Baricitinib plus Methotrexate Based on Clinical Response in the Phase 3 RA-BEGIN Study

van der Heijde D, Durez P, Schett G, Naredo E, Østergaard M, Meszros G, De Leonardis F, De La Torre I, López-Romero P, Schlichting D, Nantz E, Fleichmann R.
Clinical Rheumatology 2018;37:2381–90 DOI 10.1007/s10067-018-4221-0

Patients with active RA and little or no prior DMARD treatment, who achieved sustained clinical responses, were less likely to show structural damage progression, irrespective of treatment. RA-BEGIN was a 52-week double-blind, multicentre Phase 3 trial, which assessed the safety and efficacy of BARI as monotherapy or in combination with MTX versus MTX monotherapy, in RA patients with no or limited prior DMARDs use.1-4 This post-hoc analysis evaluated the structural damage progression in patients...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Lipid Profile and Effect of Statin Treatment in Pooled Phase II and Phase III Baricitinib Studies

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

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 o...

Keywords: JAK, Baricitinib, Real World, Cardiovascular

Efficacy of Monotherapy with Biologics and JAK inhibitors for the Treatment of Rheumatoid Arthritis: A Systematic Review

Emery P, Pope JE, Kruger K, Lippe R, DeMasi R, Lula S, Kola B.
ADV Ther 2018; 35(10):1525–63 DOI: 10.1007/s12325-018-0757-2

The b/tsDMARDs evaluated in this systematic literature review (SLR) were shown to be efficacious as monotherapies, although combination therapies usually achieved better treatment outcomes. Current treatment guidelines recommend combining b/tsDMARDs with MTX in the treatment of RA; however, up to a third of patients are treated with monotherapy. While previous SLRs1–3 have compared the efficacy of b/tsDMARD mono- versus MTX combination therapy they covered a limited number of randomised co...

Keywords: JAK, Baricitinib, Clinical, Efficacy

August 18

Adverse Events, Clinical Considerations and Management Recommendations in Rheumatoid Arthritis Patients Treated with JAK Inhibitors

Atzeni F, Talotta R, Nucera V, Marino F, Gerratana E, Sangari D, Masala IF, Sarzi-Puttini P.
Exp Rev Clin Immunol 2018 Nov;14(11):945-956. DOI: 10.1080/1744666X.2018.1504678

Janus kinase (JAK) inhibitors are efficacious in patients with moderate-to-severe RA and have a favourable safety profile. However adverse events (AE), in particular infections, are associated with the use of JAK inhibitors. This paper reviews the mechanism behind JAK inhibitors, the AEs associated with them, and provides consideration in the management of AEs in clinical practice. Data on two RA approved JAK inhibitors – tofacitinib (TOF) and baricitinib (BARI) – was obtained usin...

Keywords: JAK, Tofacitinib, Clinical, Safety

July 18

Thromboembolism with Janus Kinase (JAK) Inhibitor for Rheumatoid Arthritis: How Real is the Risk?

Scott IC, Hider SL, Scott DL.
Drug Safety 2018 Jul;41(7):645–53

Current data suggests that JAK inhibitors may increase the risk of thromboembolism and pulmonary thrombosis (PT) in RA. Two JAK inhibitors – baricitinib (BARI) and tofacitinib (TOF) – are considered effective treatments for RA, however, there are concerns about the thromboembolic risks associated with them. In August 2017, the summary of product characteristics for BARI was revised to include a warning of developing DVT and pulmonary embolism (PE), with recommendations that BARI sho...

Keywords: JAK, Baricitinib, Clinical, Safety

June 18

Effects of Baricitinib on Radiographic Progression of Structural Joint Damage at 1 year in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Synthetic Disease-modifying Antirheumatic Drugs

van der Heijde D, Dougados M, Chen YC, Greenwald M, Drescher E, Klar R, Xie L, de la Torre I, Rooney TP, Witt SL, Schlichting DE, de Bono S, Emery P.
RMD Open. 2018 May 8;4(1):e000662. DOI: 10.1136/rmdopen-2018-000662

Once daily baricitinib (BARI) inhibited radiographic progression of structural joint damage in patients with an inadequate response or intolerance to csDMARDs over 48 weeks. Current treatment goals aim to use DMARDs to inhibit structural joint damage and prevent long-term functional disability. In RA-BUILD¹, BARI was shown to significantly reduce radiographic joint damage progression in patients with active RA, with an intolerance or inadequate response to csDMARDs. Here, the authors repor...

Keywords: JAK, Baricitinib, Clinical, Radiographic

May 18

Analysis of Spontaneous Postmarket Case Reports Submitted to the FDA Regarding Thromboembolic Adverse Events and JAK Inhibitors

Verden A, Dimbil M, Kyle R, Overstreet B, Hoffman KB.
Drug Saf 2018 Apr; 41(4):357–61 DOI: 10.1007/s40264-017-0622-2

Thromboembolic-related adverse events (AEs) were, in general, not considered a class-wide safety concern after analysis of tofacitinib (TOF) and ruxolitinib (RUX) clinical data, though pulmonary thrombosis is considered a potential class-wide safety issue and portal vein thrombosis was considered a potential safety issue for RUX. During analysis of baricitinib (BARI) clinical trial data, the FDA expressed concerns regarding thromboembolic events. Following this, the CHMP have recently added a ...

Keywords: JAK, Tofacitinib, Clinical, Safety

April 18

Baricitinib for Previously Treated Moderate or Severe Rheumatoid Arthritis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Ren S, Bermejo I, Simpson E, Wong R, Scott DL, Young A, Stevenson M.
Pharmacoeconomics 2018 Jul; 36(7):769–78

In this National Institute for Health and Care (NICE) single technology appraisal of baricitinib (BARI) monotherapy and combination therapy with methotrexate (MTX), BARI efficacy was considered comparable to bDMARDs and a cost-effective use of National Health Service (NHS) resources. NICE is an independent organisation responsible for providing national guidance on health technologies in England. To be recommended by NICE, the company must provide evidence to prove BARI’s effectiveness, b...

Keywords: JAK, Baricitinib, Clinical, Phase 3

March 18

Response to Baricitinib based on Prior Biologic Use in Patients with Refractory Arthritis

Genovese MC, Kremer JM, Kartman CE, Schlichting DE, Xie L, Carmack T, Pantojas C, Burston JS, Tony HP, Macias WL, Rooney TP, Smolen JS.
Rheumatology (Oxford) 2018 May; 57(5):900-908

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...

Keywords: JAK, Baricitinib, Clinical, Efficacy

December 17

JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases

Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ.
Nat Rev Drug Discov 2017;16:843–62 DOI: 10.1038/nrd.2017.201

Janus kinases (JAKs) are essential mediators of downstream signaling pathways in many inflammatory and autoimmune diseases. This review summarizes current clinical data on first- and second-generation JAK inhibitors (jakinibs) and discusses their use for the treatment of immune and inflammatory conditions. First generation jakinibs such as tofacitinib, baricitinib, and ruxolitinib, non-selectively inhibit JAK-dependent pro-inflammatory cytokines, which are major contributors to immunopathology. ...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

November 17

Safety and Efficacy of Baricitinib in Elderly Patients with Rheumatoid Arthritis

Fleischmann R, Alam J, Arora V, Bradley J, Schlichting DE, Muram D, Smolen JS.
RMD Open. 2017; 3(2): e000546. doi: 10.1136/rmdopen-2017-000546

In this post hoc analysis of pooled data from two randomised controlled trials, RA-BUILD and RA-BEAM, age was shown not to be a contraindication for use of baricitinib. Patients in RA-BUILD were csDMARD-inadequate responder(IR) patients who received an oral placebo or 2 mg or 4 mg baricitinib once daily. Patients in RA-BEAM were MTX-IR patients and received an oral placebo, 4 mg baricitinib once daily or subcutaneous adalimumab every 2 weeks. Efficacy and safety of baricitinib in elderly patie...

Keywords: JAK, Baricitinib, Clinical, Phase 3

October 17

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

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

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, mode...

Keywords: JAK, Baricitinib, Clinical, PRO

September 17

Patient-reported Outcomes from a Phase 3 Study of Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis: Secondary Analyses from the RA-BEAM Study

Keystone EC, Taylor PC, Tanaka Y, Gaich C, DeLozier AM, Dudek A, Velasco Zamora J, Covarrubias Cobos JA, Rooney T, de Bono S, Arora V, Linetzky B, Weinblatt ME.
Ann Rheum Dis 2017;76(11):1853-1861. doi: 10.1136/annrheumdis-2017-211259

This paper describes the patient-reported outcome (PRO) data collected in RA-BEAM, a Phase 3 study of baricitinib compared with both placebo and adalimumab in patients with RA and an inadequate response to MTX. PRO measures evaluated include health-related quality of life (HRQOL), physical function, disability, fatigue, sleep, mental health status, work productivity and work activity impairment. The RA-BEAM study demonstrated that patients treated with baricitinib experienced a greater impro...

Keywords: JAK, Baricitinib, Clinical, PRO

Safety and Efficacy of Baricitinib through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis

Keystone EC, Genovese MC, Schlichting DE, de la Torre I, Beattie SD, Rooney TP, Taylor PC.
J Rheumatol. 2018 Jan;45(1):14-21. doi: 10.3899/jrheum.161161

This open-label extension (OLE) of a Phase 2b randomised controlled trial (RCT) found that safety data collected over 2 years of treatment were generally consistent with previous findings for baricitinib in RA. In the RCT, baricitinib demonstrated significant improvement in disease activity compared with placebo and an acceptable safety profile in patients with RA and an inadequate response to MTX. Patients who completed the 24-week double-blind period of the study were eligible for the OLE. Ra...

Keywords: JAK, Baricitinib, Clinical, Phase 2

April 17

EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-modifying Antirheumatic Drugs: 2016 Update

EULAR RA Management Task Force Smolen J, Landewé R, Bijlsma J, et al.
Ann Rheum Dis Published Online First: 06March2017. doi:10.1136/annrheumdis-2016-210715

The EULAR 2016 recommendations update, based on three systematic literature reviews (SLRs) and expert opinion, comprises four overarching principles and 12 recommendations compared with 14, respectively, in 2013. These recommendations intend to inform regarding EULAR’s most recent consensus on the management of RA, with the aim of attaining the best outcomes with current therapies. All DMARD types: csDMARDs, bDMARDs, tsDMARD and bsDMARD are addressed, and cost aspects are taken into consi...

February 17

Baricitinib in Patients with Inadequate Response or Intolerance to Conventional Synthetic DMARDs: Results from the RA-BUILD Study

Dougados M, van der Heijde D, Chen Y-C, Greenwald M, Drescher E, Liu J, Beattie S, Witt S, de la Torre I, Gaich C, Rooney T, Schlichting D, de Bono S, Emery P.
Ann Rheum Dis 2017;76:88–95.

Baricitinib improved symptoms of RA in the RA-BUILD trial, a Phase 3 study of baricitinib in patients with moderately to severely active RA, refractory to or intolerant to csDMARDs. As well as providing a short-term (24 weeks) benefit, there appeared to be joint damage benefit, considered a marker of long-term disability. RA-BUILD was a 24-week randomised, double-blind, placebo-controlled parallel-group study. Patients were randomised 1:1:1 to receive once-daily doses of placebo (n=228) or bari...

Keywords: JAK, Baricitinib, Clinical, Phase 3

January 17

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

Kremer J, Genovese MC, Keystone E, Taylor PC, Zuckerman SH, Ruotolo G, Schlichting DE, Crotzer VL, Nantz E, Beattie SD and Macias WL.
Arthritis Rheumatol 2017. DOI 10.1002/art.40036.

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 m...

Keywords: JAK, Baricitinib, Clinical, Phase 2

December 16

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

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

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) to MTX 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, baricit...

Keywords: JAK, Baricitinib, Clinical, Phase 3

July 16

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

Tanaka Y, Emoto K, Cai Z, et al.
J Rheumatol. 2016;43(3):504–511.

Clinical trials have shown baricitinib once daily to be effective in patients with RA. However, this Janus kinase (JAK) 1/JAK2 inhibitor has not been evaluated in a Japanese population. In this 12-week, placebo-controlled study, 145 Japanese patients were enrolled and received placebo, 1 mg, 2 mg, 4 mg or 8 mg oral baricitinib daily. Efficacy results were encouraging and consistent with earlier trials. Significantly more baricitinib patients achieved ACR20 response at Week 12 of treatment compa...

Keywords: JAK, Baricitinib, Clinical, Phase 3

May 16

Baricitinib in Patients with Refractory Rheumatoid Arthritis

Genovese et al.
N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247

For patients who have an inadequate response or unacceptable side effects associated with biologic DMARDs, the options for treatment beyond conventional DMARDs are limited. This phase 3 trial of the JAK 1/2 inhibitor, baricitinib, studied its efficacy in bDMARD-IR patients. 527 patients were randomized to either baricitinib 2mg, 4mg or placebo for up to 24 weeks. At week 12 the primary endpoints were tested hierarchically to control type 1 error; these endpoints were ACR20, HAQ-DI score, DAS28...

Keywords: JAK, Baricitinib, Clinical, Phase 3

January 15

The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers

Shi JG, Chen X, Lee F, Emm T, Scherle PA, Lo Y, Punwani N, Williams WV, Yeleswaram S.
Mod J Clin Pharmacol. 2014 Dec;54(12):1354-61. doi: 10.1002/jcph.354.

Current biologic therapies for RA, such as biologic cytokine inhibitors, which selectively target inflammatory molecules with an exquisite degree of specificity, are not clinically effective in all patients with rheumatoid arthritis. As such, there remains an unmet clinical need for more effective and better tolerated therapies. Baricitinib (LY3009104, also previously known as INCB028050) is a potent and selective small molecule inhibitor of JAK1/2, which play an important role in cytokine signa...

Keywords: JAK, Baricitinib, Preclinical, PK-PD

December 14

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

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.
Ann Rheum Dis. 2015;74(2):333–340

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 baricitinib, fo...

Keywords: JAK, Baricitinib, Clinical, Phase 2

October 13

Proposal for a new nomenclature of disease-modifying antirheumatic drugs

Smolen JS et al.
Ann Rheum Dis 2013. doi: 10.1136/annrhuemdis-2013-204317

With the recent emergence of new therapeutics for rheumatoid arthritis, new nomenclature for disease-modifying antirheumatic drugs (DMARDs) may be needed to more accurately describe the new agents. Currently, DMARDs are divided into two broad groups: synthetic DMARDs (sDMARDs) and biological DMARDs (bDMARDs). The authors propose dividing synthetic DMARDs into conventional synthetic DMARDs (csDMARDs) which would encompass traditional DMARDs (e.g. methotrexate, leflunomide), and targeted synthetic...

Keywords: Cytokine Signalling

June 13

Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050

Fridman JS, Scherle PA, Collins R, et al.
Journal of Immunology 2010; 184(9):5298-307

This preclinical characterisation study examined the efficacy and tolerability of the small molecule INCB028050 (now known as baricitinib), an orally bioavailable, selective Janus kinase (JAK) 1/JAK2 inhibitor, in rodent models of arthritis. The decision to investigate its effects of INCB028050 followed positive evidence for the related compound ruxolitinib, the JAK inhibitor tofacitinib and the IL-6 inhibitor tocilizumab in rheumatoid arthritis (RA). In this preclinical study, INCB028050 was sh...

Keywords: JAK, Baricitinib, Preclinical, Selectivity