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Arthritis & Rheumatology DOI 10.1002/art.40054
Peficitinib, a JAK inhibitor, in combination with limited conventional synthetic DMARDs in the treatment of moderate-to-severe rheumatoid arthritis Running title: Peficitinib treatment in moderate-to-severe RA Mark C. Genovese, MD1, Maria Greenwald, MD2, Christine Codding, MD3, Anna Zubrzycka-Sienkiewicz, MD4, Alan J. Kivitz, MD5, Annie Wang, PhD6, Kathyjo Shay, BA6, Xuegong Wang, MD6, Jay P. Garg, MD6, Mario H. Cardiel, MD, MSc7 Affiliations: 1Stanford University, Palo Alto, CA, USA; 2Desert Medical Advances, Palm Desert, CA, USA; 3Health Research of Oklahoma, Oklahoma City, OK, USA; 4
ARS Rheumatica sp.z.o.o, Reumatika, Warsaw, Poland; 5Altoona Center for Clinical
Research, Duncansville, PA, USA;
6
Astellas Pharma Global Development,
Northbrook, IL, USA; 7Centro de Investigación Clínica de Morelia SC, Morelia, Mexico. Corresponding author: Mark Genovese, Division of Immunology and Rheumatology, Stanford University, 1000 Welch RD #203, Palo Alto CA 94304, USA. Tel.: (650) 498-4528; Fax: (650) 723-9656; Email: [email protected]. Sources of support: The study was sponsored by Astellas Pharma Inc.; medical writing support was funded by Astellas Pharma Inc. Conflicting interests: Mark Genovese: Grants/contracts – Astellas Pharma US Inc., AbbVie Inc., Johnson & Johnson, Pfizer, Eli Lilly and Co, Vertex Pharmaceuticals Inc. Consulting – Astellas Pharma US Inc., AbbVie Inc., Johnson & Johnson, Pfizer, Eli Lilly and Co, Vertex Pharmaceuticals, Galapagos NV, Gilead Sciences Inc. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/art.40054 © 2017 American College of Rheumatology Received: Apr 15, 2016; Revised: Dec 21, 2016; Accepted: Jan 17, 2017 This article is protected by copyright. All rights reserved.
Arthritis & Rheumatology
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Maria Greenwald: Grants – Astellas Pharma US Inc., AbbVie Inc., Amgen Inc., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co, Fuji Pharma Co, Galapagos NV, Eli Lilly and Co, Pfizer, Merck & Co Inc., UCB SA. Mario Cardiel: Principal investigator or speaker – Roche Holding Ltd., Pfizer, Astellas Pharma US Inc., Bristol-Myers Squibb Co, Amgen Inc., Anthera Pharma, Janssen, Sanofi SA, Merck & Co Inc. Anna Zubrzycka-Sienkiewicz: Grants/personal fees – Astellas Pharma US Inc., Janssen, Roche Holding Ltd., UCB SA, Galapagos NV, Auven Therapeutics, Mabion SA, Celltrion Inc., Janssen Biotech Inc., Merck & Co Inc. Consulting – Astellas Pharma US Inc. Alan Kivitz: Principal investigator or speaker – Astellas Pharma US Inc., AbbVie Inc., Johnson & Johnson, Pfizer, Vertex Pharmaceuticals Inc., Eli Lilly and Co, Galapagos NV, Genentech. Consultant – Pfizer, Genentech. Christine Codding: Principal investigator – Astellas Pharma US Inc., AbbVie Inc., Amgen Inc., Bristol-Myers Squibb Co, Galapagos NV, Genentech, Eli Lilly and Co, Pfizer, Sanofi SA. Jay Garg, Kathyjo Shay, Annie Wang, Xuegong Wang: Employees of Astellas Pharma US Inc.
2 John Wiley & Sons This article is protected by copyright. All rights reserved.
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Arthritis & Rheumatology
Abstract (word count=234): Objective. To evaluate the efficacy and safety of orally administered once-daily peficitinib in patients with moderate-to-severe rheumatoid arthritis (RA) in combination with limited conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Methods. In this double-blind, randomized, phase IIb trial, patients with RA (N=289) were treated with peficitinib 25 mg, 50 mg, 100 mg, 150 mg, or matching placebo once daily for 12 weeks. Primary endpoint was the percentage of patients achieving an American College of Rheumatology (ACR) 20% response at Week 12. Results. ACR20 response rates at Week 12 were 22.0%, 36.8%, 48.3% (P
Arthritis & Rheumatology DOI 10.1002/art.40054
Peficitinib, a JAK inhibitor, in combination with limited conventional synthetic DMARDs in the treatment of moderate-to-severe rheumatoid arthritis Running title: Peficitinib treatment in moderate-to-severe RA Mark C. Genovese, MD1, Maria Greenwald, MD2, Christine Codding, MD3, Anna Zubrzycka-Sienkiewicz, MD4, Alan J. Kivitz, MD5, Annie Wang, PhD6, Kathyjo Shay, BA6, Xuegong Wang, MD6, Jay P. Garg, MD6, Mario H. Cardiel, MD, MSc7 Affiliations: 1Stanford University, Palo Alto, CA, USA; 2Desert Medical Advances, Palm Desert, CA, USA; 3Health Research of Oklahoma, Oklahoma City, OK, USA; 4
ARS Rheumatica sp.z.o.o, Reumatika, Warsaw, Poland; 5Altoona Center for Clinical
Research, Duncansville, PA, USA;
6
Astellas Pharma Global Development,
Northbrook, IL, USA; 7Centro de Investigación Clínica de Morelia SC, Morelia, Mexico. Corresponding author: Mark Genovese, Division of Immunology and Rheumatology, Stanford University, 1000 Welch RD #203, Palo Alto CA 94304, USA. Tel.: (650) 498-4528; Fax: (650) 723-9656; Email: [email protected]. Sources of support: The study was sponsored by Astellas Pharma Inc.; medical writing support was funded by Astellas Pharma Inc. Conflicting interests: Mark Genovese: Grants/contracts – Astellas Pharma US Inc., AbbVie Inc., Johnson & Johnson, Pfizer, Eli Lilly and Co, Vertex Pharmaceuticals Inc. Consulting – Astellas Pharma US Inc., AbbVie Inc., Johnson & Johnson, Pfizer, Eli Lilly and Co, Vertex Pharmaceuticals, Galapagos NV, Gilead Sciences Inc. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/art.40054 © 2017 American College of Rheumatology Received: Apr 15, 2016; Revised: Dec 21, 2016; Accepted: Jan 17, 2017 This article is protected by copyright. All rights reserved.
Arthritis & Rheumatology
Page 2 of 42
Maria Greenwald: Grants – Astellas Pharma US Inc., AbbVie Inc., Amgen Inc., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co, Fuji Pharma Co, Galapagos NV, Eli Lilly and Co, Pfizer, Merck & Co Inc., UCB SA. Mario Cardiel: Principal investigator or speaker – Roche Holding Ltd., Pfizer, Astellas Pharma US Inc., Bristol-Myers Squibb Co, Amgen Inc., Anthera Pharma, Janssen, Sanofi SA, Merck & Co Inc. Anna Zubrzycka-Sienkiewicz: Grants/personal fees – Astellas Pharma US Inc., Janssen, Roche Holding Ltd., UCB SA, Galapagos NV, Auven Therapeutics, Mabion SA, Celltrion Inc., Janssen Biotech Inc., Merck & Co Inc. Consulting – Astellas Pharma US Inc. Alan Kivitz: Principal investigator or speaker – Astellas Pharma US Inc., AbbVie Inc., Johnson & Johnson, Pfizer, Vertex Pharmaceuticals Inc., Eli Lilly and Co, Galapagos NV, Genentech. Consultant – Pfizer, Genentech. Christine Codding: Principal investigator – Astellas Pharma US Inc., AbbVie Inc., Amgen Inc., Bristol-Myers Squibb Co, Galapagos NV, Genentech, Eli Lilly and Co, Pfizer, Sanofi SA. Jay Garg, Kathyjo Shay, Annie Wang, Xuegong Wang: Employees of Astellas Pharma US Inc.
2 John Wiley & Sons This article is protected by copyright. All rights reserved.
Page 3 of 42
Arthritis & Rheumatology
Abstract (word count=234): Objective. To evaluate the efficacy and safety of orally administered once-daily peficitinib in patients with moderate-to-severe rheumatoid arthritis (RA) in combination with limited conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Methods. In this double-blind, randomized, phase IIb trial, patients with RA (N=289) were treated with peficitinib 25 mg, 50 mg, 100 mg, 150 mg, or matching placebo once daily for 12 weeks. Primary endpoint was the percentage of patients achieving an American College of Rheumatology (ACR) 20% response at Week 12. Results. ACR20 response rates at Week 12 were 22.0%, 36.8%, 48.3% (P
