TY - JOUR
T1 - Tofacitinib in patients with ankylosing spondylitis
T2 - A phase II, 16-week, randomised, placebo-controlled, dose-ranging study
AU - Van Der Heijde, Désirée
AU - Deodhar, Atul
AU - Wei, James C.
AU - Drescher, Edit
AU - Fleishaker, Dona
AU - Hendrikx, Thijs
AU - Li, David
AU - Menon, Sujatha
AU - Kanik, Keith S.
N1 - Publisher Copyright:
© Published by the BMJ Publishing Group Limited.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Objectives To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). Methods In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10â €..mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Results Emax model analysis of the primary endpoint predicted a tofacitinib 10â €..mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5â €..mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10â €..mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10â €..mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Conclusions Tofacitinib 5 and 10â €..mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. Trial registration number NCT01786668.
AB - Objectives To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). Methods In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10â €..mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Results Emax model analysis of the primary endpoint predicted a tofacitinib 10â €..mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5â €..mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10â €..mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10â €..mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Conclusions Tofacitinib 5 and 10â €..mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. Trial registration number NCT01786668.
KW - Ankylosing Spondylitis
KW - Disease Activity
KW - Magnetic Resonance Imaging
KW - Treatment
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U2 - 10.1136/annrheumdis-2016-210322
DO - 10.1136/annrheumdis-2016-210322
M3 - Article
C2 - 28130206
AN - SCOPUS:85011343425
SN - 0003-4967
VL - 76
SP - 1340
EP - 1347
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 8
ER -