Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors

results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial

Peter Nash, Bruce Kirkham, Masato Okada, Proton Rahman, Benard Combe, Gerd Ruediger Burmester, David H. Adams, Lisa Kerr, Chin Lee, Catherine L. Shuler, Mark Genovese, Khalid Ahmed, Jeffrey Alper, Nichol Barkham, Ralph E. Bennett, Francisco Javier Blanco García, Ricardo Blanco Alonso, Howard B. Blumstein, Michael S. Brooks, Gerd Rüdiger Burmester & 66 others Patricia Cagnoli, Paul H. Caldron, Alain Cantagrel, Der Yuan Chen, Melvin A. Churchill, Christine E. Codding, Benard Combe, Peter M.G. Deane, Jose Del Giudice, Atul A. Deodhar, Rajat K. Dhar, Eva Dokoupilova, Rita M. Egan, Andrea Everding, Eva Galíndez, Mark Genovese, David H. Goddard, Alice Gottlieb, Philippe Goupille, Robert M. Griffin, Ramesh C. Gupta, Stephen Hall, Kalpita Hatti, Mary P. Howell, Yu Huei Huang, Ramina Jajoo, Namieta M. Janssen, Uta Kiltz, Alan J. Kivitz, Steven J. Klein, Mariusz P. Korkosz, Roshan Kotha, Joel M. Kremer, Cummins Lue, José Luis Marenco de la Fuente, Helena Marzo-Ortega, Jordi Gratacós Masmitja, Philip J. Mease, Pier Luigi Meroni, Eric C. Mueller, Anupama C. Nandagudi, Peter Nash, Antonio Fernández-Nebro, Clark M. Neuwelt, Ana Maria Orbai, Meera R. Oza, Deborah L. Parks, Debendra Pattanaik, Maria E. Rell-Bakalarska, David Rosmarin, Euthalia Roussou, Anna I. Rychlewska-Hanczewksa, David H. Sikes, Michael T. Stack, Prashanth Sunkureddi, Hasan Tahir, Diamant Thaçi, Tsen Fang Tsai, Anthony M. Turkiewicz, Leonore Unger, Raúl Veiga Cabello, Ulf Wagner, Cheng Chung Wei, Alvin F. Wells, Peter Youssef, Agnieszka Zielinska

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Background Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. Methods In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295. Findings Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4–45·2]; p<0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1–39.8]; p<0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported. Interpretation Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab. Funding Eli Lilly and Company.

Original languageEnglish (US)
Pages (from-to)2317-2327
Number of pages11
JournalThe Lancet
Volume389
Issue number10086
DOIs
StatePublished - Jun 10 2017

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LY2439821
Psoriatic Arthritis
Tumor Necrosis Factor-alpha
Placebos
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors : results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. / Nash, Peter; Kirkham, Bruce; Okada, Masato; Rahman, Proton; Combe, Benard; Burmester, Gerd Ruediger; Adams, David H.; Kerr, Lisa; Lee, Chin; Shuler, Catherine L.; Genovese, Mark; Ahmed, Khalid; Alper, Jeffrey; Barkham, Nichol; Bennett, Ralph E.; García, Francisco Javier Blanco; Alonso, Ricardo Blanco; Blumstein, Howard B.; Brooks, Michael S.; Burmester, Gerd Rüdiger; Cagnoli, Patricia; Caldron, Paul H.; Cantagrel, Alain; Chen, Der Yuan; Churchill, Melvin A.; Codding, Christine E.; Combe, Benard; Deane, Peter M.G.; Del Giudice, Jose; Deodhar, Atul A.; Dhar, Rajat K.; Dokoupilova, Eva; Egan, Rita M.; Everding, Andrea; Galíndez, Eva; Genovese, Mark; Goddard, David H.; Gottlieb, Alice; Goupille, Philippe; Griffin, Robert M.; Gupta, Ramesh C.; Hall, Stephen; Hatti, Kalpita; Howell, Mary P.; Huang, Yu Huei; Jajoo, Ramina; Janssen, Namieta M.; Kiltz, Uta; Kivitz, Alan J.; Klein, Steven J.; Korkosz, Mariusz P.; Kotha, Roshan; Kremer, Joel M.; Lue, Cummins; de la Fuente, José Luis Marenco; Marzo-Ortega, Helena; Masmitja, Jordi Gratacós; Mease, Philip J.; Meroni, Pier Luigi; Mueller, Eric C.; Nandagudi, Anupama C.; Nash, Peter; Fernández-Nebro, Antonio; Neuwelt, Clark M.; Orbai, Ana Maria; Oza, Meera R.; Parks, Deborah L.; Pattanaik, Debendra; Rell-Bakalarska, Maria E.; Rosmarin, David; Roussou, Euthalia; Rychlewska-Hanczewksa, Anna I.; Sikes, David H.; Stack, Michael T.; Sunkureddi, Prashanth; Tahir, Hasan; Thaçi, Diamant; Tsai, Tsen Fang; Turkiewicz, Anthony M.; Unger, Leonore; Cabello, Raúl Veiga; Wagner, Ulf; Wei, Cheng Chung; Wells, Alvin F.; Youssef, Peter; Zielinska, Agnieszka.

In: The Lancet, Vol. 389, No. 10086, 10.06.2017, p. 2317-2327.

Research output: Contribution to journalArticle

Nash, P, Kirkham, B, Okada, M, Rahman, P, Combe, B, Burmester, GR, Adams, DH, Kerr, L, Lee, C, Shuler, CL, Genovese, M, Ahmed, K, Alper, J, Barkham, N, Bennett, RE, García, FJB, Alonso, RB, Blumstein, HB, Brooks, MS, Burmester, GR, Cagnoli, P, Caldron, PH, Cantagrel, A, Chen, DY, Churchill, MA, Codding, CE, Combe, B, Deane, PMG, Del Giudice, J, Deodhar, AA, Dhar, RK, Dokoupilova, E, Egan, RM, Everding, A, Galíndez, E, Genovese, M, Goddard, DH, Gottlieb, A, Goupille, P, Griffin, RM, Gupta, RC, Hall, S, Hatti, K, Howell, MP, Huang, YH, Jajoo, R, Janssen, NM, Kiltz, U, Kivitz, AJ, Klein, SJ, Korkosz, MP, Kotha, R, Kremer, JM, Lue, C, de la Fuente, JLM, Marzo-Ortega, H, Masmitja, JG, Mease, PJ, Meroni, PL, Mueller, EC, Nandagudi, AC, Nash, P, Fernández-Nebro, A, Neuwelt, CM, Orbai, AM, Oza, MR, Parks, DL, Pattanaik, D, Rell-Bakalarska, ME, Rosmarin, D, Roussou, E, Rychlewska-Hanczewksa, AI, Sikes, DH, Stack, MT, Sunkureddi, P, Tahir, H, Thaçi, D, Tsai, TF, Turkiewicz, AM, Unger, L, Cabello, RV, Wagner, U, Wei, CC, Wells, AF, Youssef, P & Zielinska, A 2017, 'Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial', The Lancet, vol. 389, no. 10086, pp. 2317-2327. https://doi.org/10.1016/S0140-6736(17)31429-0
Nash, Peter ; Kirkham, Bruce ; Okada, Masato ; Rahman, Proton ; Combe, Benard ; Burmester, Gerd Ruediger ; Adams, David H. ; Kerr, Lisa ; Lee, Chin ; Shuler, Catherine L. ; Genovese, Mark ; Ahmed, Khalid ; Alper, Jeffrey ; Barkham, Nichol ; Bennett, Ralph E. ; García, Francisco Javier Blanco ; Alonso, Ricardo Blanco ; Blumstein, Howard B. ; Brooks, Michael S. ; Burmester, Gerd Rüdiger ; Cagnoli, Patricia ; Caldron, Paul H. ; Cantagrel, Alain ; Chen, Der Yuan ; Churchill, Melvin A. ; Codding, Christine E. ; Combe, Benard ; Deane, Peter M.G. ; Del Giudice, Jose ; Deodhar, Atul A. ; Dhar, Rajat K. ; Dokoupilova, Eva ; Egan, Rita M. ; Everding, Andrea ; Galíndez, Eva ; Genovese, Mark ; Goddard, David H. ; Gottlieb, Alice ; Goupille, Philippe ; Griffin, Robert M. ; Gupta, Ramesh C. ; Hall, Stephen ; Hatti, Kalpita ; Howell, Mary P. ; Huang, Yu Huei ; Jajoo, Ramina ; Janssen, Namieta M. ; Kiltz, Uta ; Kivitz, Alan J. ; Klein, Steven J. ; Korkosz, Mariusz P. ; Kotha, Roshan ; Kremer, Joel M. ; Lue, Cummins ; de la Fuente, José Luis Marenco ; Marzo-Ortega, Helena ; Masmitja, Jordi Gratacós ; Mease, Philip J. ; Meroni, Pier Luigi ; Mueller, Eric C. ; Nandagudi, Anupama C. ; Nash, Peter ; Fernández-Nebro, Antonio ; Neuwelt, Clark M. ; Orbai, Ana Maria ; Oza, Meera R. ; Parks, Deborah L. ; Pattanaik, Debendra ; Rell-Bakalarska, Maria E. ; Rosmarin, David ; Roussou, Euthalia ; Rychlewska-Hanczewksa, Anna I. ; Sikes, David H. ; Stack, Michael T. ; Sunkureddi, Prashanth ; Tahir, Hasan ; Thaçi, Diamant ; Tsai, Tsen Fang ; Turkiewicz, Anthony M. ; Unger, Leonore ; Cabello, Raúl Veiga ; Wagner, Ulf ; Wei, Cheng Chung ; Wells, Alvin F. ; Youssef, Peter ; Zielinska, Agnieszka. / Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors : results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. In: The Lancet. 2017 ; Vol. 389, No. 10086. pp. 2317-2327.
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title = "Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial",
abstract = "Background Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. Methods In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20{\%} improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295. Findings Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53{\%}] patients; effect size vs placebo 33·8{\%} [95{\%} CI 22·4–45·2]; p<0·0001) and ixekizumab every 2 weeks (59 [48{\%}] patients; 28.5{\%} [17·1–39.8]; p<0·0001) than did patients with placebo (23 [20{\%}] patients). Up to week 24, serious adverse events were reported in three (3{\%}) patients with ixekizumab every 4 weeks, eight (7{\%}) with ixekizumab every 2 weeks, and four (3{\%}) with placebo; no deaths were reported. Infections were reported in 47 (39{\%}) patients with ixekizumab every 4 weeks, 47 (38{\%}) with ixekizumab every 2 weeks, and 35 (30{\%}) with placebo. Three (2{\%}) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported. Interpretation Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab. Funding Eli Lilly and Company.",
author = "Peter Nash and Bruce Kirkham and Masato Okada and Proton Rahman and Benard Combe and Burmester, {Gerd Ruediger} and Adams, {David H.} and Lisa Kerr and Chin Lee and Shuler, {Catherine L.} and Mark Genovese and Khalid Ahmed and Jeffrey Alper and Nichol Barkham and Bennett, {Ralph E.} and Garc{\'i}a, {Francisco Javier Blanco} and Alonso, {Ricardo Blanco} and Blumstein, {Howard B.} and Brooks, {Michael S.} and Burmester, {Gerd R{\"u}diger} and Patricia Cagnoli and Caldron, {Paul H.} and Alain Cantagrel and Chen, {Der Yuan} and Churchill, {Melvin A.} and Codding, {Christine E.} and Benard Combe and Deane, {Peter M.G.} and {Del Giudice}, Jose and Deodhar, {Atul A.} and Dhar, {Rajat K.} and Eva Dokoupilova and Egan, {Rita M.} and Andrea Everding and Eva Gal{\'i}ndez and Mark Genovese and Goddard, {David H.} and Alice Gottlieb and Philippe Goupille and Griffin, {Robert M.} and Gupta, {Ramesh C.} and Stephen Hall and Kalpita Hatti and Howell, {Mary P.} and Huang, {Yu Huei} and Ramina Jajoo and Janssen, {Namieta M.} and Uta Kiltz and Kivitz, {Alan J.} and Klein, {Steven J.} and Korkosz, {Mariusz P.} and Roshan Kotha and Kremer, {Joel M.} and Cummins Lue and {de la Fuente}, {Jos{\'e} Luis Marenco} and Helena Marzo-Ortega and Masmitja, {Jordi Gratac{\'o}s} and Mease, {Philip J.} and Meroni, {Pier Luigi} and Mueller, {Eric C.} and Nandagudi, {Anupama C.} and Peter Nash and Antonio Fern{\'a}ndez-Nebro and Neuwelt, {Clark M.} and Orbai, {Ana Maria} and Oza, {Meera R.} and Parks, {Deborah L.} and Debendra Pattanaik and Rell-Bakalarska, {Maria E.} and David Rosmarin and Euthalia Roussou and Rychlewska-Hanczewksa, {Anna I.} and Sikes, {David H.} and Stack, {Michael T.} and Prashanth Sunkureddi and Hasan Tahir and Diamant Tha{\cc}i and Tsai, {Tsen Fang} and Turkiewicz, {Anthony M.} and Leonore Unger and Cabello, {Ra{\'u}l Veiga} and Ulf Wagner and Wei, {Cheng Chung} and Wells, {Alvin F.} and Peter Youssef and Agnieszka Zielinska",
year = "2017",
month = "6",
day = "10",
doi = "10.1016/S0140-6736(17)31429-0",
language = "English (US)",
volume = "389",
pages = "2317--2327",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10086",

}

TY - JOUR

T1 - Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors

T2 - results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial

AU - Nash, Peter

AU - Kirkham, Bruce

AU - Okada, Masato

AU - Rahman, Proton

AU - Combe, Benard

AU - Burmester, Gerd Ruediger

AU - Adams, David H.

AU - Kerr, Lisa

AU - Lee, Chin

AU - Shuler, Catherine L.

AU - Genovese, Mark

AU - Ahmed, Khalid

AU - Alper, Jeffrey

AU - Barkham, Nichol

AU - Bennett, Ralph E.

AU - García, Francisco Javier Blanco

AU - Alonso, Ricardo Blanco

AU - Blumstein, Howard B.

AU - Brooks, Michael S.

AU - Burmester, Gerd Rüdiger

AU - Cagnoli, Patricia

AU - Caldron, Paul H.

AU - Cantagrel, Alain

AU - Chen, Der Yuan

AU - Churchill, Melvin A.

AU - Codding, Christine E.

AU - Combe, Benard

AU - Deane, Peter M.G.

AU - Del Giudice, Jose

AU - Deodhar, Atul A.

AU - Dhar, Rajat K.

AU - Dokoupilova, Eva

AU - Egan, Rita M.

AU - Everding, Andrea

AU - Galíndez, Eva

AU - Genovese, Mark

AU - Goddard, David H.

AU - Gottlieb, Alice

AU - Goupille, Philippe

AU - Griffin, Robert M.

AU - Gupta, Ramesh C.

AU - Hall, Stephen

AU - Hatti, Kalpita

AU - Howell, Mary P.

AU - Huang, Yu Huei

AU - Jajoo, Ramina

AU - Janssen, Namieta M.

AU - Kiltz, Uta

AU - Kivitz, Alan J.

AU - Klein, Steven J.

AU - Korkosz, Mariusz P.

AU - Kotha, Roshan

AU - Kremer, Joel M.

AU - Lue, Cummins

AU - de la Fuente, José Luis Marenco

AU - Marzo-Ortega, Helena

AU - Masmitja, Jordi Gratacós

AU - Mease, Philip J.

AU - Meroni, Pier Luigi

AU - Mueller, Eric C.

AU - Nandagudi, Anupama C.

AU - Nash, Peter

AU - Fernández-Nebro, Antonio

AU - Neuwelt, Clark M.

AU - Orbai, Ana Maria

AU - Oza, Meera R.

AU - Parks, Deborah L.

AU - Pattanaik, Debendra

AU - Rell-Bakalarska, Maria E.

AU - Rosmarin, David

AU - Roussou, Euthalia

AU - Rychlewska-Hanczewksa, Anna I.

AU - Sikes, David H.

AU - Stack, Michael T.

AU - Sunkureddi, Prashanth

AU - Tahir, Hasan

AU - Thaçi, Diamant

AU - Tsai, Tsen Fang

AU - Turkiewicz, Anthony M.

AU - Unger, Leonore

AU - Cabello, Raúl Veiga

AU - Wagner, Ulf

AU - Wei, Cheng Chung

AU - Wells, Alvin F.

AU - Youssef, Peter

AU - Zielinska, Agnieszka

PY - 2017/6/10

Y1 - 2017/6/10

N2 - Background Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. Methods In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295. Findings Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4–45·2]; p<0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1–39.8]; p<0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported. Interpretation Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab. Funding Eli Lilly and Company.

AB - Background Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors. Methods In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295. Findings Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4–45·2]; p<0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1–39.8]; p<0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported. Interpretation Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab. Funding Eli Lilly and Company.

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U2 - 10.1016/S0140-6736(17)31429-0

DO - 10.1016/S0140-6736(17)31429-0

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VL - 389

SP - 2317

EP - 2327

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10086

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