Golimumab, a human antibody to tumour necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study
- E C Keystone1,
- M C Genovese2,
- L Klareskog3,
- E C Hsia4,5,
- S T Hall6,
- P C Miranda7,
- J Pazdur8,
- S-C Bae9,
- W Palmer10,
- J Zrubek4,
- M Wiekowski11,
- S Visvanathan4,
- Z Wu4,
- M U Rahman4,5
- 1University of Toronto and Mount Sinai Hospital, Toronto, Ontario, Canada
- 2Stanford University, Palo Alto, California, USA
- 3Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden
- 4Centocor Research and Development, Inc, Malvern, Pennsylvania, USA
- 5University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
- 6Cabrini Medical Centre, Malvern, South Australia, Australia
- 7Universidad de Chile and Hospital San Juan de Dios, Santiago, Chile
- 8Instytut Reumatologii, Warszawa, Poland
- 9Department of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea
- 10Westroads Medical Group, Omaha, Nebraska, USA
- 11Schering-Plough Research Institute, Kenilworth, New Jersey, USA
- Professor E Keystone, Mount Sinai Hospital, 60 Murray Street, Room 2-006, Toronto, Ontario MST 3L9, Canada;
- Accepted 23 November 2008
- Published Online First 9 December 2008
Objective: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.
Methods: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.
Results: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.
Conclusion: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.
Competing interests: Declared. ECK, MCG, LK, STH, PCM, JP, SCB and WP (or their institutions) have received research grants from Centocor and/or Schering-Plough. LK and ECK have received consulting fees from Centocor and/or Schering-Plough. ECH, JZ, SV, ZW and MUR are employees of Centocor Research and Development, Inc and own stock and/or stock options in Johnson&Johnson, Inc. MW is an employee of and owns stock in Schering-Plough Research Institute, Inc.
Funding: This study was funded by Centocor Research and Development, Inc, a wholly owned subsidiary of Johnson&Johnson, Inc and Schering Plough Research Institute, Inc.
The following investigators participated in the GO-FORWARD study: Argentina: Alejandro Alvarellos (Córdoba), Alejandra Magdelena Babinin (Córdoba), Juan Carlos Barreira (Cuidad Autonoma de Buenos Aires), Alberto Berman (Tucman), Maria Alicia Lázaro (Buenos Aires), Ingrid Strusberg (Córdoba), Guillermo Alberto Tate (Buenos Aires), Osvaldo Hübscher (Cuidad Autonoma de Buenos Aires), Bernardo Antonio Pons Estel (Santa Fé); Australia: Stephen Hall (Malvern, VIC), Geoffrey Owen Littlejohn (Clayton, VIC), Peter Thomas Nash (Maroochydore and Cotton Tree, QLD); Canada: Christopher Atkins (Victoria, BC), André Beaulieu (Ste-Foy, QC), Alfred Cividino (Hamilton, ON), Edward Keystone (Toronto, ON), Majed Khraishi (St John’s, NL), Robert McKendry (Ottawa, ON); Chile: Pedro Claudio Miranda Cabezas (Santiago), Ana Flores Torterolo (Rancagua), Irmgadt Annelise Goecke (Santiago), Maria Loreto Massardo Vega (Santiago), Juan Pablo Riedemann Gonzalez (Temuco); Germany: Holm Häntzschel (Leipzig), Rolf W Hauer (Berlin), Gunther Neeck (Rostock), Andrea Rubbert (Köln), Jürgen Wollenhaupt (Hamburg), Reinhold Ernst Schmidt and Henning Zeidler (Hanover); Hungary: László Hodinka (Budapest); Mexico: Jorge Antonio Esquivel Valerio (Monterrey, NL); New Zealand: Daniel Wai Tho Ching (Timaru), Nicola Dalbeth (Auckland), Peter Brian Barrie Jones (Rotorua); Poland: Jan Brzezicki (Elblag), Marek Stefan Brzosko (Szczecin), Zbigniew Adam Mencel (Kalisz), Anna Fillipowicz-Sosnowska (Warszawa), Hanna Chwalińska-Sadowska (Warszawa), Jacek Andrzej Pazdur (Warszawa); South Korea: Sang Cheol Bae (Seoul), Hyun Ah Kim (Kyunggi-do), Sung II Kim (Seo-Gu), Choong Ki Lee (Nam-gu Daegu), Soo Kon Lee (Seoul), Yeong Wook Song (Seoul); Republic of China: Tien-Tsai Cheng (Taiwan); USA: Antony Hou and Eugene P Boling (Upland, CA), Richard D Brasington, Jr (St Louis, MO), Melvin A Churchill, Jr (Lincoln, NE), Gino DiVittorio (Mobile, AL), John E Ervin (Kansas City, MO), Mark Genovese (Palo Alto, CA), Mitchell Lowenstein (Palm Harbor, FL), Michael Miniter (Moline, IL), Frederick T Murphy (North Duncansville, PA), William Palmer (Omaha, NE), Irene Tong (Pasadena, CA), Yong Tsai (Ormond Beach, FL), Christopher Wise (Richmond, VA).
▸ Additional supplemental material is published online only at http://ard.bmj.com/content/vol68/issue6
Ethics approval: The protocol was reviewed and approved by each site’s institutional review board or ethics committee.
Patient consent: Obtained.