Publications

Pain Reduction in Rheumatoid Arthritis Patients Who Use Opioids: A Post Hoc Analysis of Phase 3 Trials of Baricitinib

ACR Open Rheumatol. 2021. Epub ahead of print. doi: 10.1002/acr2.11380

Pope JE,

Lee YC,

Curtis JR,

Mo D,

Xie L,

Dickson CL,

Schlichting DE,

Cardoso A,

Simon LS,

Taylor PC

This post hoc analysis shows that pain reduction was similar between opioid users and nonusers with baricitinib 2 mg and 4 mg, but not adalimumab.Use of opioids to treat RA-related pain has increased, yet long-term use has been associated with reduced efficacy and safety concerns. In addition, the misuse of opioids has resulted in a public health crisis in the United States and highlights the need for safe, effective nonaddictive alternatives for pain management. As such, Pope, et al. assessed p...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Pain

Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database

Ann Rheum Dis. 2021. Epub ahead of print. doi: 10.1136/annrheumdis-2021-221276.

Taylor PC,

Takeuchi T,

Burmester GR,

Durez P,

Smolen JS,

Deberdt W,

Issa M,

Terres JR,

Bello N,

Winthrop KL

Analysis of data from the highest level of patient exposure to baricitinib across the spectrum of the RA population demonstrates that baricitinib maintained a similar safety profile to earlier analyses, with no new safety signals identified.Using integrated data from nine randomised controlled trials, Taylor, et al. assessed the safety of baricitinib 2 mg and 4 mg once-daily. Analysis of data from 3770 patients (median 4.6 years, up to 9.3 years) with active RA showed that baricitinib maintained...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• LTE

Median Time to Pain Improvement and the Impact of Baseline Pain Severity on Pain Response in Patients with Psoriatic Arthritis Treated with Tofacitinib

RMD Open. 2021;7(2):e001609.

de Vlam K,

Ogdie A,

Bushmakin AG,

Cappelleri JC,

Fleischmann R,

Taylor PC,

Azevedo V,

Fallon L,

Woolcott J,

Mease PJ.

Tofacitinib 5 mg twice daily provides clinically meaningful improvements in pain for patients with PsA.Reducing pain is a primary treatment concern for patients with PsA. As such, de Vlam, et al. set out to evaluate the time to pain improvement and the impact of baseline pain severity on pain response in patients with PsA receiving tofacitinib.Using data from the OPAL Broaden and OPAL Beyond trials, they discovered that clinically important improvements in pain were experienced by more patients,...

Keywords:

• JAK,
• Tofacitinib,
• PRO / QoL,
• Pain

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

Rheumatology (Oxford). 2021;60(5):2256-2266.

Smolen JS,

Xie L,

Jia B,

Taylor PC,

Burmester G,

Tanaka Y,

Elias A,

Cardoso A,

Ortmann R,

Walls C,

Dougados M.

Baricitinib 4mg may be considered for long-term treatment of early and refractory rheumatoid arthritis following results demonstrating efficacy and tolerability for up to 3 years.Smolen JS, et al. analysed data from two completed 52-week, phase III studies, RA-BEGIN (DMARD-naïve) and RA-BEAM (MTX-IR), and one ongoing long-term extension study (RA-BEYOND) – providing data for 148 weeks in total. Results demonstrated that the long-term maintenance of clinically relevant treatment goals, including ...

Keywords:

• JAK,
• Baricitinib,
• LTE,
• Efficacy

The JAK/STAT Pathway: A Focus on Pain in Rheumatoid Arthritis

Semin Arthritis Rheum. 2021 Feb;51(1):278-284

Simon LS,

Taylor PC,

Choy EH,

Sebba A,

Quebe A,

Knopp KL,

Porreca F

Many cytokines associated with RA pathogenesis and pain are affected directly or indirectly by the JAK/STAT pathway, therapeutic targeting may offer promise. Having better understanding of these mechanisms can help clinicians make treatment decisions that optimise the control of inflammation and pain. However, pain in patients with RA is complex and involves multiple driving mechanisms that may differentially occur over time in different people. Although one known constant is that nociceptive ac...

Keywords:

• JAK,
• Basic Science,
• 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

Filgotinib, a JAK1 Inhibitor, Modulates Disease Related Biomarkers in Rheumatoid Arthritis: Results from Two Randomized, Controlled Phase 2b Trials

Rheumatol Ther. 2020 DOI: 10.1007/s40744-019-00192-5

Tarrant JM,

Galien R,

Wanying L,

Goyal L,

Pan Y,

Hawtin R,

Zhang W,

Van der Aa A and Taylor PC

In this study examining the effect of FIL on a panel of biomarkers, FIL down-modulated several key inflammatory mediators of signalling pathways in RA - independent of MTX background therapy. This confirmed the strong network effects of the JAK1 node in autoimmunity, matrix and cartilage degradation, angiogenesis, and leukocyte adhesion and recruitment. Biomarkers key to RA pathophysiology were measured at baseline, Wk4 and Wk12 in FIL 100 mg, FIL 200 mg or PBO treatment groups from two phase 2b...

Keywords:

• JAK,
• Filgotinib,
• Phase 2,
• MOA,
• Biomarkers

Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM

J Clin Med. 2019 Sep 5;8(9). pii: E1394

Fautrel B,

Kirkham B,

Pope JE,

Takeuchi T,

Gaich C,

Quebe A,

Zhu B,

de la Torre I,

De Leonardis F,

Taylor PC

Post hoc analyses from RA-BEAM concluded that BARI 4 mg QD or ADA 40 mg Q2W resulted in improvements in pain, physical function, fatigue and work productivity in patients with RA, independent of the treatment’s impact on inflammation. Among patients achieving remission or LDA, greater improvements in pain and physical function were seen with BARI than with ADA or PBO.Of 1010 patients included in the analysis at Week 24, 168 were in remission, 310 were in remission/LDA and 700 were not in remissi...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• Pain

Comparison of Baricitinib, Upadacitinib, and Tofacitinib Mediated Regulation of Cytokine Signalling in Human Leukocyte Subpopulations

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,
• Updacitinib,
• MOA

Clinical Outcomes in Patients Switched from Adalimumab to Baricitinib Due to Non-Response and/or Study Design: Phase III Data in Patients with Rheumatoid Arthritis

Ann Rheum Dis. 2019 Jul;78(7):890-898.

Tanaka Y,

Fautrel B,

Keystone EC,

Ortmann RA,

Xie L,

Zhu B,

Issa M,

Patel H,

Gaich CL,

de Bono S,

Rooney TP,

Taylor PC

Switching from ADA to BARI without a lengthy washout period can be executed with acceptable safety and tolerability and was associated with maintained disease control. Switching therapies in RA is commonplace in myriad scenarios including inadequate responses, intolerances and patient preference. Assessing the safety and efficacy of new treatments such as BARI, in the context of use as a replacement therapy, is beneficial. A previous study (RA-BEACON) has demonstrated that safely switching from ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3