Publications

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

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

Sustained Response Following Discontinuation of Methotrexate in Patients with Rheumatoid Arthritis Treated with Subcutaneous Tocilizumab

Arthritis Rheumatol 2018;70:1200–08 DOI 10.1002/art.40493

Kremer JM,

Rigby W,

Singer NG,

Birchwood C,

Gill D,

Reiss W,

Pei J,

Michalska M

The COMP-ACT study showed patients achieving low disease activity (LDA) with tocilizumab (TCZ) plus methotrexate (MTX) can discontinue MTX, while maintaining disease control for up to 16 weeks.Previous studies have shown TCZ to be efficacious as a monotherapy or in combination with MTX in patients with RA1,2. Patients frequently discontinue taking DMARDs, such as MTX, due to intolerance or adverse events.COMP-ACT is a randomised, double-blind, 52-week study evaluating the sustained efficacy of s...

Tocilizumab Discontinuation After Attaining Remission in Patients with Rheumatoid Arthritis who were Treated with Tocilizumab Alone or in Combination with Methotrexate: Results from a Prospective Randomised Controlled Study (the second year of the SURPRISE study)

Ann Rheum Dis 2018; 77:1268–1275 DOI: 10.1093/rheumatology/key121

Kaneko Y,

Kato M,

Tanaka Y,

Inoo M,

Kobayashi-Haraoka H,

Amano K,

Miyata M,

Murakawa Y,

Yasuoka H,

Hirata S,

Tanaka E,

Miyasaka N,

Yamanaka H,

Yamamoto K,

Takeuchi T,

the SURPRISE study group

The second-year results from the SURPRISE study show that low disease activity (LDA) can be maintained after discontinuation of tocilizumab with continued methotrexate after remission is achieved. Discontinuation of biologic agents in patients who have achieved remission or low disease activity (LDA) is desirable from a risk–benefit point of view. Compared with TNF inhibitors, little is known regarding TCZ-free remission or LDA, but studies indicate that only a small proportion of patients remai...

Keywords:

• IL-12,
• Tocilizumab,
• Phase 3,
• Persistence

Two Years of Sarilumab in Patients with Rheumatoid Arthritis and an Inadequate Response to MTX: Safety, Efficacy and Radiographic Outcomes

Rheumatology 2018;57:1423–1431 DOI: 10.1093/rheumatology/key121

Genovese MC,

van Adelsberg J,

Fan C,

Graham NMH,

van Hoogstraten H,

Parrino J,

Mangan EK,

Spindler A,

Huizinga TWJ,

van der Heijde D,

for the EXTEND study investigators

Two-year treatment of active, moderate-to-severe RA with sarilumab, along with dose reduction in the event of laboratory abnormalities, resulted in durable efficacy outcomes and a safety profile consistent with previous reports involving IL-6R inhibition. Durable long-term safety and efficacy, reduced joint damage progression, and conserving health-related quality of life and work productivity are important goals of therapy in RA.1 Sarilumab significantly reduced disease activity, improved physi...

Keywords:

• IL-6,
• Sarilumab,
• Phase 3,
• Safety,
• Radiographic

Safety and Efficacy of Upadacitinib in Patients with Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (SELECT-NEXT): a Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial

Lancet 2018;391:2503–12

Burmester GR,

Kremer JM,

Van den Bosch F,

Kivitz A,

Bessette L,

Li Y,

Zhou Y,

Othman AA,

Pangan AL,

Camp HS

Patients with moderate-to-severe active RA had significant improvements in clinical signs and symptoms with upadacitinib (UPA) compared with placebo.In Phase 2 studies, UPA showed favourable efficacy when administered twice daily as an immediate-release formulation at doses of 6–12 mg in patients with active RA who had TNFi-IR.1,2 An extended-release formulation allowing once-daily (QD) administration was developed for Phase 3 studies. SELECT-NEXT was a double-blind, multicentre, Phase 3 study t...

Keywords:

• JAK,
• Upadacitinib,
• Phase 3

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis

Rheumatol Ther 2018 Jun; 5(1):203–14. DOI: 10.1007/s40744-018-0093-7

Fleischmann R,

Wollenhaupt J,

Cohen S,

Wang L,

Fan H,

Bandi V,

Andrews J,

Takiya L,

Bananis E,

Weinblatt ME

Methotrexate (MTX) or Glucocorticoid (GC) discontinuation has little effect on CDAI response in patients given tofacitinib (TOF) for up to 3 years. Patients receiving TOF who showed initial improvements benefitted from initiation of MTX or GCs. Concomitant treatments such as MTX or GC are commonly used in combination with RA therapies to improve or accelerate clinical responses. However, their use is associated with many adverse events so clinicians aim to use them for a minimal duration.This po...

Keywords:

• JAK,
• Tofacitinib

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

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

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

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, moderate le...

Keywords:

• JAK,
• Baricitinib,
• PRO / QoL

The Safety and Immunogenicity of Live Zoster Vaccination in Rheumatoid Arthritis Patients Before Starting Tofacitinib: A Randomized Phase II Trial

Arthritis Rheumatol. 2017 Oct;69(10):1969-1977. doi: 10.1002/art.40187

Winthrop KL,

Wouters A,

Choy E,

Soma K,

Hodge J,

Nduaka C,

Biswas P,

Needle E,

Passador MS,

Mojcik C,

Rigby W

Patients with RA who started treatment with tofacitinib 2–3 weeks after being vaccinated against herpes zoster had similar varicella zoster virus (VZV)-specific humoral and cell-mediated responses to the live vaccine compared to patients who received placebo.In this Phase 2 study, humoral and cell-mediated immune responses were evaluated before receipt of live zoster vaccine (LZV) and at 2, 6 and 14 weeks after vaccination, having been randomised to tofacitinib 5 mg BID or placebo, 2–3 weeks aft...

Keywords:

• JAK,
• Tofacitinib,
• Vaccination,
• Infections

A Comparison of Discontinuation Rates of Tofacitinib and Biologic Disease-modifying Anti-rheumatic Drugs in Rheumatoid Arthritis: a Systematic Review and Bayseian Network Meta-analysis Regression

Clin Exp Rheumatol 2017;35:689–99

Park JS-K,

Lee MY,

Jang E-J,

Kim H-L,

Ha D-M,

Lee E-K

Based on a Bayesian network meta-analysis (NMA) in patients with RA who previously showed failure with csDMARDs or biologics, discontinuation rates between tofacitinib (TOF) and biologics (TNFis, abatacept [ABT], rituximab [RTX] and tocilizumab [TCZ]) differed based on previous treatments and reasons for discontinuation.Data were collected from randomised controlled trials (RCT) found from literature searches from the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE. Disconti...

Keywords:

• JAK,
• Tofacitinib,
• Meta analysis,
• Persistence

Efficacy and Safety of Tofacitinib Monotherapy, Tofacitinib with Methotrexate, and Adalimumab with Methotrexate in Patients with Rheumatoid Arthritis (ORAL Strategy): A Phase 3b/4, Double-Blind, Head-To-Head, Randomised Controlled Trial

Lancet. 2017 Jul 29;390(10093):457-468. doi: 10.1016/S0140-6736(17)31618-5

Fleischmann R,

Mysler E,

Hall S,

Kivitz A,

Moots R,

Luo Z,

DeMasi R,

Soma K,

Zhang R,

Takiya L,

Tatulych S,

Mojcik C,

Krishnaswami S,

Menon S,

Smolen J,

on behalf of the ORAL Strategy investigators

In this first head-to-head non-inferiority trial assessing a JAKi ± MTX directly compared with a TNFi + MTX in patients with RA, tofacitinib (TOF) + MTX showed non-inferiority to adalimumab (ADA) + MTX. Non-inferiority was not shown for TOF monotherapy versus TOF + MTX, or versus ADA + MTX.In this 52-week study, MTX-inadequate responder (IR) patients were randomised 1:1:1 to receive TOF 5 mg BID monotherapy, TOF 5 mg BID + MTX or ADA 40 mg every other week + MTX. The primary endpoint, ACR50 resp...

Keywords:

• JAK,
• Tofacitinib,
• Phase 4,
• Phase 3