[Show abstract][Hide abstract]ABSTRACT: Introduction:
Golimumab is a human anti-TNF monoclonal antibody that was derived from human antibody-transgenic mice. Golimumab demonstrated meaningful clinical benefit and tolerable safety in patients with active rheumatoid arthritis (RA) who were methotrexate (MTX)-naïve, or who inadequately responded to MTX or who had previously been treated with a TNF inhibitor. Areas covered: This review summarizes published data on the clinical efficacy and safety for golimumab (including its pharmacodynamic and pharmacokinetic characteristics) from multiple global phase 3 and Japanese phase 2/3 clinical trials. In the long term extension of three Phase 3 studies with subcutaneous golimumab the reported retention rate is high. Expert opinion: Golimumab binds TNF with high affinity and can be delivered subcutaneously every 4 weeks. Like other IgG1 antibodies, FcR functions suggests that antibody dependent cellular cytotoxicity is observed but the contribution of cell lysis to efficacy is unclear. Although anti-TNFα agents made it possible to achieve clinical remission in RA patients, there is still an unmet need to develop treatments that will enable them to discontinue all RA medication and maintain drug-free remission.
Article · Jan 2016 · Expert Opinion on Drug Metabolism & Toxicology
[Show abstract][Hide abstract]ABSTRACT: Objectives:
To assess the influence of golimumab dosage and disease activity on joint destruction in patients with active rheumatoid arthritis (RA) in the GO-FORTH study.
Efficacy was compared among groups given basal methotrexate plus placebo, golimumab (50 mg), or golimumab (100 mg) with stratification by high (HDA) or moderate (MDA) baseline disease activity and by high or low baseline C-reactive protein (CRP).
Among HDA or high CRP patients, the mean change of the total Sharp score was 3.48 and 3.41 in the placebo group, 1.94 and 2.71 in the 50 mg group, and 0.39 and 1.15 in the 100 mg group, respectively. The percentage of progression-free patients with HDA or high CRP was 40.4% and 40.0%, 43.1% and 38.2%, and 69.8% and 61.5%, respectively. Among MDA or low CRP patients, both golimumab doses showed similar prevention of joint destruction. Among HDA or high CRP patients, a shorter disease duration and higher TSS/disease duration ratio were associated with joint destruction.
Both doses of golimumab (50 or 100 mg) prevented joint destruction in MDA or low CRP patients, but 100 mg was better for HDA or high CRP patients with a shorter disease duration or higher TSS/disease duration ratio.
[Show abstract][Hide abstract]ABSTRACT: Objective:
To evaluate the safety and efficacy of golimumab+methotrexate(MTX) in Japanese patients with active rheumatoid arthritis (RA).
Japanese patients with active RA despite MTX were randomized to placebo+MTX (Group1, n=88), golimumab 50mg+MTX (Group2, n=86), or golimumab 100mg+MTX (Group3, n=87). Patients with <20% improvement in swollen/tender joint counts entered early escape at week16. At week 24, all remaining placebo patients crossed over to golimumab 50mg. Efficacy assessments included ACR20, DAS28-ESR, and HAQ-DI. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score.
ACR20 response rates in Group1, Group2, and Group3 were 67.9%, 86.1%, and 82.4%, respectively, at week52 and were maintained through week 104 (87.1%, 94.0%, and 88.7%) and week156 (97.1%, 94.1%, and 89.5%). Proportions of patients with good/moderate DAS28-ESR response or clinically meaningful improvement in HAQ-DI were also maintained through week 156. The majority of patients did not experience radiographic progression through week156. Among 257 golimumab-treated patients, 251 (97.7%) had ≤1 AE; 54 (21.0%) had ≤1 serious AE through week156. Infections were the most common type of AE.
Response to golimumab+MTX was maintained over 3 years in Japanese patients with active RA despite MTX. Safety results were consistent with the known safety profile of golimumab.
[Show abstract][Hide abstract]ABSTRACT: Objective
To evaluate the efficacy and safety of golimumab 50 and 100 mg monotherapy in Japanese patients with active rheumatoid arthritis (RA) despite treatment with disease-modifying antirheumatic drugs (DMARDs).
A total of 316 patients were randomised to receive subcutaneous injections every 4 weeks of placebo (group 1), golimumab 50 mg (group 2) or golimumab 100 mg (group 3); group 1 crossed over to golimumab 50 mg at week 16. The primary end point was the proportion of patients achieving ≥20% improvement in the American College of Rheumatology criteria (ACR20) at week 14. ACR50 and ACR70 response rates were also measured. Adverse events (AEs) were monitored throughout the study.
Demographics were similar across groups; the mean age was 52 years and 81.8% of patients (252/308) were female. Week 14 ACR20 response rates were significantly greater in groups 2 (51/101 (50.5%)) and 3 (60/102 (58.8%)) than in group 1 (20/105 (19.0%); p<0.0001 for both), as were ACR50 and ACR70 response rates. After placebo crossover at week 16, week 24 ACR response rates were similar in groups 1 and 2. Through week 16, 63.8% of patients in group 1, 62.4% in group 2 and 60.8% in group 3 had AEs and 1.9%, 1.0% and 2.0% had serious AEs. After week 16, one malignancy was reported (breast cancer, group 3). Infections were the most common AEs. No deaths or cases of tuberculosis were reported through week 24.
Golimumab monotherapy (50 and 100 mg) was effective in reducing the signs and symptoms of RA in Japanese patients with active disease despite DMARD treatment.
Full-text available · Article · Sep 2012 · Annals of the rheumatic diseases
[Show abstract][Hide abstract]ABSTRACT: To assess the efficacy and safety of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA).
269 Japanese patients with active RA despite treatment with MTX were randomised (1:1:1) to placebo + MTX (Group 1), golimumab 50 mg + MTX (Group 2) or golimumab 100 mg + MTX (Group 3). Subcutaneous golimumab/placebo was injected every 4 weeks; stable doses of oral MTX (6-8 mg/week) were continued. Patients were allowed to enter early escape (Group 1 added golimumab 50 mg, Group 2 increased golimumab to 100 mg, Group 3 continued golimumab 100 mg) based on swollen/tender joint counts at week 14. The primary study endpoint was achievement of at least 20% improvement in the American College of Rheumatology (ACR20) response criteria at week 14. To control for multiplicity of testing, treatment group comparisons were first made between combined Groups 2 and 3 versus Group 1, followed by comparisons of Group 2 and Group 3 versus Group 1.
The proportion of patients with an ACR20 response at week 14 was significantly higher in combined Groups 2 and 3 (73.4%, 127/173) and in each of Group 2 (72.1%, 62/86) and Group 3 (74.7%, 65/87) compared with Group 1 (27.3%, 24/88; p<0.0001 for all comparisons). Golimumab + MTX also elicited a significantly better response than placebo + MTX in other efficacy parameters, including disease activity score (DAS28) response/remission and radiographic assessments. During the 16-week fixed treatment regimen study period, 72.7%, 75.6% and 78.2% of patients had adverse events and 1.1%, 1.2% and 2.3% had serious adverse events in Groups 1, 2 and 3, respectively.
In Japanese patients with active RA despite MTX therapy, golimumab + MTX was significantly more effective than MTX monotherapy in reducing RA signs/symptoms and limiting radiographic progression with no unexpected safety concerns.
Full-text available · Article · Nov 2011 · Annals of the rheumatic diseases