Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis.
OBJECTIVE
To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis (RA).


METHODS
MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1).


RESULTS
An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P=0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P=0.049) and between group 3 (40.5%; P=0.038) but not group 4 (36.5%; P=0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound -5.2%; predefined delta value for noninferiority -10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively.


CONCLUSIONS
Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns.
Emery
Paul
P
University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, [corrected] Leeds, UK. p.emery@leeds.ac.uk
Fleischmann
Roy M
RM
Moreland
Larry W
LW
Hsia
Elizabeth C
EC
Strusberg
Ingrid
I
Durez
Patrick
P
Nash
Peter
P
Amante
Eric Jason B
EJ
Churchill
Melvin
M
Park
Won
W
Pons-Estel
Bernardo Antonio
BA
Doyle
Mittie K
MK
Visvanathan
Sudha
S
Xu
Weichun
W
Rahman
Mahboob U
MU
D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D007279:Injections, Subcutaneous; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C529000:golimumab; D008727:Methotrexate