Maintenance of Clinical and Radiographic Benefit With Intravenous Golimumab Therapy in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy: Week-112 Efficacy and Safety Results of the Open-Label Long-Term Extension of a Phase III, Double-Blind, Randomized, Placebo-Controlled Trial.

Abstract

OBJECTIVE:

To evaluate the safety, efficacy, pharmacokinetics, immunogenicity, and radiographic progression through 2 years of treatment with intravenous (IV) golimumab plus methotrexate (MTX) in an open-label extension of a phase III trial of patients with active rheumatoid arthritis (RA) despite MTX therapy.

METHODS:

In the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, 592 patients with active RA were randomized (2:1) to intravenous golimumab 2 mg/kg plus MTX (Group 1) or placebo plus MTX (Group 2) at weeks 0 and 4, then every 8 weeks thereafter; placebo patients crossed over to golimumab at week 16 (early escape) or week 24 (crossover). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology 20%, 50%, 70% (ACR20, ACR50, ACR70) response criteria, 28-joint count disease activity score using the C-reactive protein level (DAS28-CRP), physical function and quality of life measures, and changes in the modified Sharp/van der Heijde scores (SHS). Safety was monitored through week 112.

RESULTS:

In total, 486 patients (82.1%) continued treatment through week 100, and 68.1%, 43.8%, and 23.5% had an ACR20/50/70 response, respectively, at week 100. Clinical response and improvements in physical function and quality of life were generally maintained from week 24 through 2 years. Mean change from baseline to week 100 in SHS score was 0.74 in Group 1 and 2.10 in Group 2 (P = 0.005); progression from week 52 to week 100 was clinically insignificant in both groups. A total of 481 patients completed the safety followup through week 112; 79.1% had an adverse event, and 18.2% had a serious adverse event.

CONCLUSION:

Clinical response to IV golimumab plus MTX was maintained through week 100. Radiographic progression following golimumab treatment was clinically insignificant between week 52 and week 100. No unexpected adverse events occurred through week 112, and the safety profile was consistent with anti-tumor necrosis factor therapy.

• Authors: Clifton O Bingham 3rd, Alan M Mendelsohn, Lilianne Kim, Zhenhua Xu, Jocelyn Leu, Chenglong Han, Kim Hung Lo, Rene Westhovens, Michael E Weinblatt, GO-FURTHER Investigators
• Journal: Arthritis care & research (Arthritis Care Res (Hoboken)) Vol. 67 Issue 12 Pg. 1627-36 (Dec 2015) ISSN: 2151-4658 [Electronic] United States
• PMID: 25623393 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Chemical References

• Antibodies, Monoclonal
• Antirheumatic Agents
• Biomarkers
• Inflammation Mediators
• C-Reactive Protein
• golimumab
• Methotrexate

Topics

• Administration, Intravenous
• Antibodies, Monoclonal (administration & dosage, adverse effects, pharmacokinetics)
• Antirheumatic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Arthritis, Rheumatoid (blood, diagnostic imaging, drug therapy, physiopathology)
• Biomarkers (blood)
• Blood Sedimentation
• C-Reactive Protein (metabolism)
• Cross-Over Studies
• Disability Evaluation
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Humans
• Inflammation Mediators (blood)
• Methotrexate (administration & dosage, adverse effects, pharmacokinetics)
• Quality of Life
• Radiography
• Recovery of Function
• Surveys and Questionnaires
• Time Factors
• Treatment Outcome