Two-Year Efficacy and Safety of Infliximab Treatment in Patients with Active Psoriatic Arthritis: Findings of the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT)

CHRISTIAN E. ANTONI, ARTHUR KAVANAUGH, DÉSIRÉE van der HEIJDE, ANNA BEUTLER, GREGORY KEENAN, BEI ZHOU, BRUCE KIRKHAM, ZUHRE TUTUNCU, GERD R. BURMESTER, UDO SCHNEIDER, DANIEL E. FURST, JERRY MOLITOR, EDWARD KEYSTONE, DAFNA D. GLADMAN, BERNHARD MANGER, SIEGFRIED WASSENBERG, RALF WEIER, DANIEL J. WALLACE, MICHAEL H. WEISMAN, JOACHIM R. KALDEN, and JOSEF S. SMOLEN

ABSTRACT.

Objective. To investigate longterm efficacy/safety of infliximab over 2 years in patients with active psoriatic arthritis (PsA).

Methods. Initially, 104 patients were randomized to receive blinded infusions of infliximab 5 mg/kg or placebo at Weeks 0, 2, 6, and 14. At Week 16, all patients received infliximab 5 mg/kg every 8 weeks through Week 46. Seventy-eight of the 87 patients completing the first year continued into the open-label longterm extension and received infliximab 5 mg/kg at Weeks 54, 62, 70, 78, 86, and 94. The primary efficacy endpoint for the study extension was the proportion of patients with at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at Week 98. Radiographic progression was assessed by the PsA-modified van der Heijde-Sharp score in patients with radiographs available at baseline and Week 98 (n = 43).

Results. At Week 98, 62% (48/78) of infliximab-treated patients achieved an ACR20 response; 45% (35/78) and 35% (27/78) of patients achieved ACR50 and ACR70 responses, respectively. Among patients with baseline Psoriasis Area and Severity Index scores >= 2.5, 64% (16/25) achieved > 75% improvement from baseline to Week 98. The average estimated annual radiographic progression with infliximab treatment was significantly reduced versus the estimated baseline rate of progression. No new safety issues were observed during the second year of the study.

Conclusion. Therapy with infliximab 5 mg/kg through Week 94 produced sustained improvement in joint and skin symptoms, inhibited radiographic progression, and continued to exhibit a favorable benefit-risk ratio in this population with treatment-refractory PsA. (J Rheumatol First Release Mar 15 2008)

Key Indexing Terms:

INFLIXIMAB
PSORIATIC ARTHRITIS
PSORIASIS
TUMOR NECROSIS FACTOR-a

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From Schering-Plough Corporation, Kenilworth, New Jersey; Jefferson School of Medicine UCLA, Los Angeles; Cedars-Sinai Medical Center, Los Angeles; Center for Innovative Therapy, the University of California San Diego, La Jolla, California; Virginia Mason Clinic, Seattle, Washington; Centocor, Inc., Malvern, Pennsylvania, USA; Leiden University Medical Center, Leiden, The Netherlands; Guy's Hospital, London, United Kingdom; Charité University Medicine, Berlin; Evangelisches Fachkrankenhaus, Ratingen, Germany; University of Toronto, Toronto, Ontario, Canada; Medical University of Vienna and Lainz Hospital, Vienna, Austria.

Supported in part by NIH grant M01 RR00827 to the UCSD GCRC and an unrestricted grant from Centocor, Inc. to the Department of Medicine III, University Erlangen, Erlangen, Germany. Schering Plough Research Institute provided study medication and additional support.

C.E. Antoni, MD, Group Director, Clinical Immunology; B. Manger, MD, Professor of Rheumatology; J.R. Kalden, MD, Director Emeritus, Departments of Internal Medicine III and Molecular Immunology, Schering-Plough Corporation, formerly of Friedrich Alexander University, Erlangen-Nürnberg, Germany; A. Kavanaugh, MD, Professor of Medicine; Z. Tutuncu, MD, Division of Rheumatology, Allergy and Immunology, Center for Innovative Therapy, the University of California San Diego; D. van der Heijde, MD, PhD, Professor of Rheumatology, Leiden University Medical Center; A. Beutler, MD, Senior Director, Clinical Research; G. Keenan, MD, Executive Director, Immunology; B. Zhou, PhD, Associate Director, Biostatistics, Centocor, Inc.; B. Kirkham, MD, FRCP, FRACP, Clinical Lead, Rheumatology/Lupus, Department of Rheumatology, Guy's Hospital; G.R. Burmester, MD, Professor of Medicine, Director, Department of Rheumatology and Clinical Immunology; U. Schneider, MD, Professor, Charité University Medicine; D.E. Furst, MD, Carl M. Pearson Professor of Rheumatology, Jefferson School of Medicine, UCLA; J. Molitor, MD, PhD, Associate Director, Clinical Research Program, Virginia Mason Clinic; E. Keystone, MD, FRCPC, Professor of Medicine; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto; S. Wassenberg, MD, Department of Rheumatology; R. Weier, MD, Department of Rheumatology, Evangelisches Fachkrankenhaus; D.J. Wallace, MD, Clinical Professor of Medicine, Division of Rheumatology; M.H. Weisman, MD, Director, Division of Rheumatology, Cedars-Sinai Medical Center; J.S. Smolen, MD, Division of Rheumatology, Internal Medicine III, Medical University of Vienna and Lainz Hospital.

Address reprint requests to Dr. C. Antoni, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0530, USA. E-mail: christian.antoni@spcorp.com

Accepted for publication December 11, 2007.