Publications

Pontos importantes no tratamento de doenças inflamatórias imunomediadas com inibidores de Janus Quinasa: uma revisão sistemática da literatura

RMD Open 2020;6:e001374 doi:10.1136/rmdopen-2020-001374

Kerschbaumer A,

Smolen JS,

Nash P,

Doerner T,

Dougados M,

Fleischmann R,

Geissler K,

McInnes IM,

Takeuchi T,

Trauner M,

Winthrop K,

de Wit M,

Boehncke W-H,

Falzon L,

van der Heijde D

Trials of JAKi have been conducted in many therapy areas, including rheumatology, dermatology and gastroenterology. In 2019, a task force was set up to create a consensus to guide clinicians on how to use JAKi in clinical practice. This systematic literature review conducted in 2019 support this consensusIn line with EULAR’s standardised operating procedures for recommendations, a literature search was conducted in EMBASE, Medline and the Cochrane Library databases. To evaluate the efficacy of t...

Keywords:

• JAK,
• Review

Trocando entre o Inibidor de Janus Quinase Upadacitinib e Adalimumab Depois de Resposta Insuficiente: eficácia e segurança em pacientes com artrite reumatoide

Ann Rheum Dis 2020; doi:10.1136/annrheumdis-2020-21841220

Fleischmann RM,

Blanco R,

Hall S,

Thomson GTD,

Van den Bosch FE,

Zerbini C,

Bessette L,

Enejosa J,

Li Y,

Song Y,

DeMasi R,

Song I-H

Both ACR and EULAR recommend adding a biologic or targeted synthetic DMARD in patients who do not achieve treatment goals at follow-up. Findings indicated that an immediate switch in mechanism of action (from JAKi to TNFi and vice versa) following treat-to-target principles is feasible with minimal risk of flare regardless of whether patients are switched due to non-response or incomplete-response.SELECT-COMPARE followed treat-to-target principles to examine the efficacy of switching in two pati...

Keywords:

• JAK,
• TNF,
• Upadacitinib,
• Adherence,
• Switching

Infecções nos Ensaios Clínicos de Baricitinib em Pacientes com Artrite Reumatoide Ativa

Annals of the Rheumatic Diseases, May 2020

Winthrop KL,

Harigai M,

Genovese MC,

Lindsey S,

Takeuchi T,

Fleischmann R,

Bradley JD,

Byers NL,

Hyslop DL,

Issa M,

Nishikawa A,

Rooney TP,

Witt S,

Dickson CL,

Smolen JS,

Dougados M

Baricitinib, an oral selective JAK1 and JAK2 inhibitor,8 demonstrated significant clinical efficacy in phase 3 RA trials. Pooled data from these trials, including a long-term extension (LTE), inform the safety profile for baricitinib, mainly to evaluate the incidence of infection in patients with active rheumatoid arthritis (RA), with a focus on serious infection, tuberculosis (TB), herpes zoster (HZ) and opportunistic infection (OI). The data collected were from eight double-blind randomised tr...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Infections

Eficácia e Segurança a Longo Prazo de Baricitinib com e sem Metotrexato para o Tratamento de Artrite Reumatoide: Experiência com a Continuação de Baricitinib Monoterapia ou Depois de Troca de Metotrexato Monoterapia ou Baricitinib mais Metotrexato

Arthritis Care Res (Hoboken) 2020;72(8):1112-1121

Fleischmann R,

Takeuchi T,

Schiff M,

Schlichting D,

Xie L,

Issa M,

Stoykov I,

Lisse J,

Martinez-Osuna P,

Rooney T,

Zerbini CAF

This 24-week update from the baricitinib RA-BEYOND LTE study follows patients previously treated in the pivotal study RA-BEGIN. It demonstrates the maintained safety and efficacy of baricitinib monotherapy, and the effects of concurrent MTX treatment on response rates and patient reported outcomes. Previous P3 study RA-BEGIN demonstrated the superior efficacy of 4mg baricitinib compared to MTX monotherapy up to 52 weeks, with no major safety events being identified. At the end of the trial, pati...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Safety,
• Switching

Tofacitinib em Combinação com Metotrexato em Pacientes com Artrite Reumatoide: Desfechos Reportados por Pacientes do Estudo de Fase 3 de 24 Meses ORAL Scan

Clin Exp Rheumatol . Sep-Oct 2020;38(5):848-857. Epub 2019 Dec 19.

Strand V,

van der Heijde D,

Tanaka Y,

Keystone E,

Kremer J,

Zerbini C A F,

Cardiel M H,

Cohen S,

Nash P,

Song Y-W,

Tegzová D,

Gruben D,

Wallenstein G,

Connell C A,

Fleischmann R

In the ORAL SCAN study, patients receiving TOF 5 mg or 10 mg BID reported significant improvements in patient-reported outcomes at month 3 compared with placebo, which were maintained through 24 months of treatment.RA causes a significant health and socioeconomic burden and affects all aspects of health related quality of life. ORAL Scan included patients with active RA and inadequate response to MTX who were randomised to receive TOF 5 mg or 10 mg BID plus MTX or PBO. This study evaluated the i...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• PRO / QoL

Highlights of 2019

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

McInnes. I

2019 was another remarkable year in cytokine signalling. We can be optimistic that clinical practice for inflammatory arthritis will continue to improve, with promising long-term safety data supporting the use of established JAK inhibitors; tofacitinib and baricitinib, in addition to exciting phase III clinical data for filgotinib and newly approved upadacitinib. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respecti...

Keywords:

• Review

Upadacitinib versus Placebo ou Adalimumab em Pacientes com Artrite Reumatoide e uma Resposta Inadequada a Metotrexato: Resultados de um Estudo de Fase 3, randomizado, controlado, duplo cego

Arthritis Rheumatol 2019 DOI: 10.1002/art.41032

Fleischmann R,

Pangan AL,

Song IH,

Mysler E,

Bessette L,

Peterfy C,

Durez P,

Ostor AJ,

Li Y,

Zhou Y,

Othman AA,

Genovese MC

UPA demonstrated superiority to ADA in terms of clinical, functional and patient-reported outcomes with comparable radiographic inhibition. As many RA patients fail to achieve LDA and remission with TNF inhibitors and MTX there is a requirement for additional treatment options. In this SELECT-COMPARE study the clinical and functional outcomes of UPA were compared to ADA in MTX-IR patients. 1629 MTX-IR were randomly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W or PBO, with background MTX. Key end...

Keywords:

• JAK,
• Upadacitinib,
• Phase 3

Segurança e Efetividade de Upadacitinib ou Adalimumab mais Metotrexato em Pacientes com Artrite Reumatoide Mais de 48 Semanas com Troca para Terapia Alternativa em Pacientes com Resposta Insuficiente

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215764

Fleischmann RM,

Genovese MC,

 Enejosa JV,

 Mysler E,

Bessette L,

Peterfy C,

 Ostor P,

 Li Y,

 Song I

Consistent with Wk26 data, significantly more UPA patients achieved LDA and remission versus ADA and PBO over 48 weeks. RA patients often change therapy due to inadequate response and intolerance. The SELECT COMPARE study was designed to explore switching to JAK inhibitors from TNF inhibitors without a wash-out period (and vice versa). The long-term safety and efficacy of UPA was compared to ADA and PBO in MTX-IR.1629 patients were blindly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W and PBO, wi...

Keywords:

• JAK,
• Upadacitinib,
• Phase 3

Vacina Viva Zoster em Pacientes com Artrite Reumatoide Tratados com Tofacitinib com ou sem Metotrexate, ou Adalimumab com Metotrexate

Arthritis Care and Research 2019 DOI: 10.1002/acr.24010

Calabrese LH,

Abud-Mendoza C,

Lindsey SM,

Lee SH,

Tatulych S,

Takiya L,

Iikuni N,

Soma K,

Luo Z,

Fleischmann R

Live zoster vaccine (LZV) was well tolerated, and herpes zoster (HZ) incidence rates were generally similar between treatment groups in vaccinated versus non-vaccinated patients in a subset of RA who received LZV before TOF ± MTX, or ADA + MTX, in ORAL Strategy. It is known that patient with RA are at increased risk of developing HZ though the mechanisms behind this are currently not well understood though therapies, such as TOF, are thought to increase the risk. ACR and EULAR recommend using LZ...

Keywords:

• JAK,
• Tofacitinib,
• Vaccination

Tofacitinib em combinação com o metotrexato em pacientes com artrite reumatóide: eficácia clínica, resultados radiográficos e de segurança do estudo de verificação oral de Fase 3 de 24 meses

Arthritis Rheumatol. 2019 Jun;71(6):878-891

van der Heijde D,

Strand V,

Tanaka Y,

Keystone E,

Kremer J,

Zerbini CAF,

Cardiel MH,

Stanley Cohen S,

Nash P,

Song YW,

Tegzová D,

Gruben D,

Wallenstein G,

Connell CA,

Fleischmann R; ORAL Scan investigators

RA patients receiving TOF 5 or 10 mg BID plus MTX showed sustained clinical and radiographic treatment effects through months 12-24. The safety profile was consistent with previous TOF studies. The 12-month data from the ORAL Scan study have been previously reported. This report assesses durability of responses, including structural damage progression, and safety with TOF through 24 months. Patients were randomized 4:4:1:1 to receive TOF 5 or 10 mg BID, or PBO advanced to TOF with stable, backgr...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• Radiographic