Publications

Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a Phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT)

J Am Acad Dermatol 2018;79:266–76. doi: 10.1016/j.jaad.2018.04.013

Lebwohl M,

Blauvelt A,

Paul C,

Sofen H,

Węgłowska J,

Piguet V,

Burge D,

Rolleri R,

Drew J,

Peterson L,

Augustin M

In this phase 3 study, both 200mg and 400mg certolizumab pegol doses improved psoriasis symptoms at Week 12 measured via PASI 75. Improvement was maintained, after rerandomisation, through Week 48, with a safety profile consistent with its drug class. This Phase 3 CIMPACT trial by Lebwohl et al., assessed the safety and efficacy of certolizumab pegol for the treatment of moderate-to-severe chronic plaque psoriasis.

Keywords:

• Efficacy,
• Phase 3,
• Safety,
• TNF

Professor Iain McInnes Reviews the Most Notable Papers from 2018

Please click the links below to go to the CSF review of each paper

McInnes. I

2018 brought a wealth of new data in cytokine signalling and IL-6 that helps inform current clinical practice and brings the promise of new options in the future. There was good data on the use of sub cutaneous tocilizumab as well as strategies in early RA and for methotrexate tapering. For the currently marketed JAK inhibitors, tofacitinib and baricitinib, continuous long-term efficacy and safety data further support its current use and applications. On the development side, the outcomes of the...

Keywords:

• Review

Phase 3 RA-BEGIN 試験での，メソトレキセート，バリシチニブ，またはバリシチニブとメソトレキセート併用で治療された早期関節リウマチ患者における，臨床的反応性に基づいた　構造的損傷進行

Clinical Rheumatology 2018;37:2381–90 DOI 10.1007/s10067-018-4221-0

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

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,
• Phase 3,
• Radiographic

バリシチニブ試験フェーズ IIとIIIにおける脂質プロファイルとスタチン治療の影響

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

トシリズマブ皮下注治療中の関節リウマチ患者における、メソトレキセート中止後の持続的反応

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...

関節リウマチ治療における生物学的製剤とJAK 阻害薬の単剤の有効性: システマティックレビュー

ADV Ther 2018; 35(10):1525–63 DOI: 10.1007/s12325-018-0757-2

Emery P,

Pope JE,

Kruger K,

Lippe R,

DeMasi R,

Lula S,

Kola B

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 controlle...

Keywords:

• JAK,
• Review

トシリズマブ単剤またはメトトレキサート併用で治療された関節リウマ チ患者において、寛解達成後のトシリズマブ休薬: 前向き無作為化試験結果 (SURPRISE試験2年目)

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

MTXに効果不十分の関節リウマチ患者に対するサリルマブ の2年結果: 安全性, 有効性および画像的アウトカム

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

JAK阻害薬治療中関節リウマチ患者の有害事象，臨床的配慮 およびマネージメント

Exp Rev Clin Immunol 2018 Nov;14(11):945-956. DOI: 10.1080/1744666X.2018.1504678

Atzeni F,

Talotta R,

Nucera V,

Marino F,

Gerratana E,

Sangari D,

Masala IF,

Sarzi-Puttini P

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 using PubMed, Medl...

Keywords:

• JAK,
• Safety,
• Review

関節リウマチにおけるJanus Kinase (JAK) 阻害薬の血栓塞栓: リスクの実際は?

Drug Safety 2018 Jul;41(7):645–53

Scott IC,

Hider SL,

Scott DL

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 should be used wi...

Keywords:

• JAK,
• Safety,
• Review