Cytokine Signalling Forum

Publications





February 20

Inhibición Preferencial de JAK1 en Relación a JAK 3 por Upadacitinib: Análisis de la Exposición-Respuesta de Datos Ex Vivo en 2 Ensayos Clínicos Fase 1 y Comparación con Tofacitinib

Mohamed MF, Beck D, Camp HS, Othman AA.
Pharmacodynamics. 2020

Ex vivo pharmacodynamic assay results demonstrated a greater selectivity of UPA on JAK1 versus JAK3 compared to TOF. This analysis conducted ex vivo stimulation of STAT3 phosphorylation by IL-6 as a measure of JAK1 activity and STAT5 phosphorylation by IL-7 as a measure of JAK1/JAK3 activity. Change in pSTAT3 and pSTAT5 were calculated at 1, 6 and 12 hours following drug administration using samples collected from healthy subjects and subjects with RA, from 2 phase 1 studies. Exposure-response...

Keywords: JAK, Upadacitinib, Preclinical, MOA

Translated by: Igor Kos

January 20

Upadacitinib Mejora los Resultados Reportados por los Pacientes en Pacientes con Artritis Reumatoide y Respuesta Inadecuada a Fármacos Antirreumáticos Modificadores de la Enfermedad Sintéticos Convencionales: Resultados de SELECT-NEXT

Strand V, Pope J, Tundia N, Friedman A, Camp H, Pangan A, Ganguli A, Fuldeore M, Goldschmidt D, Schiff M.
Arthritis Research & Therapy 2019

In SELECT-NEXT, UPA demonstrated clinically meaningful improvements in patient reported outcomes compared to PBO in patients with RA who had an inadequate response to csDMARDs. In this post hoc analysis, the effect of UPA 15 or 30 mg on patient reported outcomes were assessed and compared to PBO. Eligible patients (661) with an inadequate response to csDMARDs were randomly assigned 2:2:1:1 to receive background csDMARD therapy with either UPA 15 mg, UPA 30 mg or PBO. PROs collected at Wk4 and Wk...

Keywords: JAK, Upadacitinib, Clinical, PRO

Translated by: Igor Koz

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 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 ...

August 16

A Randomized Phase 2b Study of ABT-494, a Selective JAK Inhibitor in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Genovese M, Smolen J, Weinblatt M, Burmester G, Meerwein S, Camp H, Wang L, Othman A, Khan N, Pangan A, Jungerwirth S.
Arthritis Rheumatol 2016; Accepted article DOI 10.1002/art-39808 [Epub 2016]

This dose-ranging study evaluated the efficacy of the novel, selective JAK1 inhibitor ABT-494 versus placebo in patients with moderate-to-severe RA and inadequate response (IR) to MTX. In this 12-week, randomised, double-blind study (BALANCE II), the efficacy and safety of ABT-494 dosed at 3mg, 6 mg, 12 mg, 18 mg (all twice daily) and 24 mg (once daily) was assessed. Patients included had not received prior biologic therapy. Of the 299 patients included in the analysis, the proportions of pati...