Cytokine Signalling Forum

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February 21

Upadacitinib Monoterapia Versus Metotrexato Monoterapia en Pacientes Japoneses con Artritis Reumatoide Metotrexato Naïve: Un subanálisis del estudio de fase 3 SELECT-EARLY

Takeuchi T, Rischmueller M, Blanco R, Xavier RM, Ueki Y, Atsumi T, Chen S, Friedman A, Pangan AL, Strand V, van Vollenhoven RF.
Mod Rheumatol 2021;26:1–16.

In this sub-analysis of the Phase 3 SELECT-EARLY study, UPA demonstrated clinical efficacy superior to placebo in the Japanese subpopulation. Along with a favourable efficacy observed with the Japan-specific 7.5 mg dose of UPA for all secondary endpoints. SELECT-EARLY was designed to study the safety and efficacy of UPA 15 and 30mg as monotherapy, but it also included a subset of 138 Japanese patients, 40% of whom were randomised to receive UPA 7.5mg. This was designed to meet the requirements...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

January 21

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

Mease PJ, Lertratanakul A, Anderson JK, Papp K, Van den Bosch F, Tsuji S, Dokoupilova E, Keiserman M, Wang X, Zhong S, McCaskill RM, Zueger P, Pangan AL, Tillett W.
Annals of the rheumatic diseases. 2021 Mar 1;80(3):312-20.

In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA. Despite the availability of bDMARDs in PsA, only a small proportion of patients achieve the recommended target of minimal disease activity; as such, additional treatment options are needed. Upadacitinib is under evaluation for PsA. This paper reports the 24-week data...

November 20

Ensayo Clínico de Upadacitinib o Abatacept en Artritis Reumatoide

Rubbert‑Roth A, Enejosa J, Pangan AL, Haraoui B, Rischmueller M, Khan N, Zhang Y, Martin N, Xavier RM.
N Engl J Med 2020;383:1511–21 DOI: 10.1056/NEJMoa2008250

In patients with refractory RA to bDMARDs, upadacitinib was found to be superior to abatacept in DAS28-CRP change from baseline and the achievement of remission at week 12. 612 bDMARD-IR patients were randomised 1:1 to UPA 15 mg QD or ABA, each in combination with stable synthetic DMARDs. At Week 12, patients with <20% decrease in TJC and Swollen joint count (SJC) had background medication adjusted or added. All patients completing Week 24 were eligible to remain in an open-label, long-term ...

Keywords: JAK, Upadacitinib, Clinical, Efficacy

Translated by: Igor Kos

August 20

Eficacia y Seguridad de Upadacitinib Monoterapia en Pacientes Metotrexato-Naïve con Artritis Reumatoide Moderada a Grave (SELECT- EARLY): Un Ensayo Aleatorizado, Doble-ciego, con Comparador Activo Multicéntrico Internacional

van Vollenhoven R, Takeuchi T, Pangan AL, Friedman A, Mohamed MEF, Chen S, Rischmueller M, Blanco R, Xavier RM, Strand V.
Arthritis Rheumatol 2020

Upadacitinib monotherapy demonstrated superior clinical, radiographic, and patient-reported outcomes versus methotrexate in methotrexate-naïve RA patients. This 48-week double-blind active comparator study investigated upadacitinib monotherapy in patients with early RA, who were either methotrexate-naïve, or who had very limited exposure. 947 patients were randomised to once-daily upadacitinib 15 or 30 mg, or weekly methotrexate. Unusually, there were two separate primary endpoints, s...

Keywords: JAK, Upadacitinib, Efficacy

Translated by: Igor Koz

November 19

Análisis de Exposición Respuesta de Eficacia y Seguridad de Upadacitinib en Estudios de Fase 2 y 3 para Apoyar la Evaluación de Riesgo Beneficio en la Artritis Reumatoide

Nader A, Mohamed M-EF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA.
Clin Pharmacol Ther . 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671.

UPA 15 mg provided the optimal benefit-risk in RA through maximizing efficacy with only small incremental benefit with 30 mg, and with consistency across RA subpopulations and with UPA monotherapy or combination with csDMARDs. Exposure-response analyses were conducted using combined data from two Phase 2b and five Phase 3 studies in order to characterise the relationship between plasma exposure and efficacy, as well as to select safety parameters using the totality of the data in subjects with...

Keywords: JAK, Upadacitinib, Clinical, Efficacy

Translated by: Igor Kos

August 19

Upadacitinib versus Placebo o Adalimumab en Pacientes con Artritis Reumatoide y una Respuesta inadecuada a Metotrexate: Resultados de un Estudio de Fase 3, aleatorizado, controlado doble ciego

Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC.
Arthritis Rheumatol 2019 DOI: 10.1002/art.41032

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 e...

Keywords: JAK, Upadacitinib, Clinical, Efficacy

June 19

Upadacitinib as Monotherapy in Patients with Active Rheumatoid Arthritis and Inadequate Response to Methotrexate (SELECT-MONOTHERAPY): A Randomised, Placebo-Controlled, Double-Blind Phase 3 Study

Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, Zhang Y, Damjanov N, Friedman A, Othman AA, Camp HS, Cohen S.
Lancet. 2019 Jun 8;393(10188):2303-2311

UPA monotherapy showed statistically significant improvements in clinical and functional outcomes versus continuing MTX in MTX inadequate-responder patients with RA. Despite its proven effectiveness and safety, many patients are unable to tolerate MTX due to its side-effects. Therapies that can be used without concomitant MTX therefore, have an important place in RA management. In previous studies, UPA has shown efficacy in combination with stable background csDMARDs in RA patients who are DMA...

July 18

Seguridad y Eficacia de Upadacitinib en Pacientes con Artritis Reumatoide Activa Refractaria a Fármacos Anti-Reumaticos Modificadores de la Enfermedad Biológicos (SELECT-BEYOND) un Ensayo Aleatorizado Controlado Fase 3

Genovese MC, Fleischmann R, Combe B, Hall S, Rubbert-Roth A, Zhang Y, Zhou Y, Mohamed M-EF, Meerwein S, Pangan AL.
Lancet 2018;391:2513–24

Upadacitinib (UPA) extended release formulation was effective in treating patients with moderate-to-severe RA with an inadequate response to bDMARDs. Phase 2 study data has shown that UPA is an efficacious and safe treatment for active RA.1,2 SELECT-BEYOND was a double-blind, long-term extension, Phase 3 study to assess the efficacy of UPA in patients with RA who were bDMARD-IR. The first 12-weeks of SELECT-BEYOND were placebo-controlled, with a double-blind period followed by an ongoing double...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Translated by: Igor Kos

Seguridad y Eficacia de Upadacitinib en pacientes con Artritis Reumatoide con Respuesta Inadecuada a Fármacos Anti-Reumáticos Modificadores de la Enfermedad (SELECT-NEXT): un Ensayo Aleatorizado, Doble Ciego, Controlado-Placebo Fase 3

Burmester GR, Kremer JM, Van den Bosch F, Kivitz A, Bessette L, Li Y, Zhou Y, Othman AA, Pangan AL, Camp HS.
Lancet 2018;391:2503–12

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...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Translated by: Igor Kos

March 17

A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti–Tumor Necrosis Factor Therapy

Kremer JM, Emery P, Camp HS, Friedman A, Wang L, Othman AA, Khan N, Pangan AL, Jungerwirth S and Keystone EC.
Arthritis Rheumatol 2016;68:2867–77

The summary and accompanying slide deck have been developed in conjunction with the Genovese et al. study (Study 1) which examined ABT-494 in MTX-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor. Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intoleran...

Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, Wang L, Othman AA, Khan N, Pangan AL and Jungerwirth S.
Arthritis Rheumatol 2016;68:2857–66

The summary and accompanying slide deck have been developed in conjunction with the Kremer et al. study (Study 2) which examined ABT-494 in TNF-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor. Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intolerant ...