Patient Populations and Study Designs
These analyses utilized data from three double-blind, randomized, placebo-controlled, phase 3 trials of IV golimumab: GO-FURTHER (NCT00973479), GO-VIBRANT (NCT02181673), and GO-ALIVE (NCT02186873) (Figure 1). In GO-FURTHER, eligible adults with active RA (≥ 6/66 swollen joints and ≥ 6/68 tender joints) despite MTX therapy (≥ 3 months) were randomized (2:1) to receive IV golimumab 2 mg/kg at weeks 0 and 4 and every 8 weeks thereafter through week 100 or placebo infusions at weeks 0 and 4 and every 8 weeks with crossover to golimumab at week 24. Patients in the placebo group who had < 10% improvement in swollen and tender joint counts entered early escape (double-blind) at week 16 and received IV golimumab 2 mg/kg. Patients were required to continue their stable doses of concomitant MTX (15–25 mg/week) and were permitted to continue oral low-dose corticosteroid therapy (≤ 10 mg/day of prednisone or equivalent) throughout the trial.
In GO-VIBRANT, adult patients with active PsA (≥ 5/66 swollen joints, ≥ 5/68 tender joints, and C-reactive protein ≥ 0.6 mg/dL) were eligible. Patients were randomized (1:1) to receive IV golimumab 2 mg/kg at weeks 0 and 4 and every 8 weeks thereafter through week 52 or placebo infusions at weeks 0 and 4 and every 8 weeks with crossover to golimumab at week 24. Concomitant MTX (≤ 25 mg/week) was permitted for those patients who had been receiving MTX for ≥ 3 months at a stable dose for ≥ 4 weeks. At week 16, patients in both groups who had < 5% improvement in swollen and tender joint counts could enter early escape and were allowed to have one of the following treatment changes at the investigators' discretion: an increase in corticosteroid dose (total dose ≤ 10 mg/day prednisone or equivalent), MTX dose (total dose ≤ 25 mg/week), or non-steroidal anti-inflammatory drugs (NSAIDs) dose; or initiation of NSAIDs, corticosteroids (≤ 10 mg/day prednisone or equivalent), MTX (≤ 25 mg/week), sulfasalazine (≤ 3 g/day), hydroxychloroquine (≤ 400 mg/day), or leflunomide (≤ 20 mg/day).
The GO-ALIVE trial included adults with active AS (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4 and a visual analog scale [0–10 cm] score for total back pain of ≥ 4). Patients were randomized (1:1) to receive IV golimumab 2 mg/kg at weeks 0 and 4 and every 8 weeks thereafter through week 52 or placebo infusions at weeks 0 and 4 with crossover to golimumab at week 16. Patients could have received prior therapy with one TNFi other than golimumab (limited to 20% of enrollment) ≥ 3 months before the first study agent administration. Stable doses of concomitant MTX (≤ 25 mg/week), sulfasalazine, hydroxychloroquine, NSAIDs, other analgesics, and low-dose oral corticosteroids (dose equivalent to ≤ 10 mg prednisone/day) were permitted.
In all three trials, infusions were administered over approximately 30 min. Placebo-treated patients received only saline solution that did not contain excipients found in the golimumab formulation. Infusion reactions were defined as adverse events (AEs) that occurred within 1 h following infusion of the study agent. Patients were permitted prophylactic drugs (excluding corticosteroids) prior to infusion; pre-treatment was at the discretion of the investigator and typically included acetaminophen, antihistamines, and/or NSAIDs.
The trials were conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practices. Protocols were approved by an Institutional Review Board or ethics committees for each site, and all patients provided written informed consent.
Safety was monitored throughout the trials, with final safety assessments at week 112 in GO-FURTHER and week 60 in GO-VIBRANT and GO-ALIVE or at specified times after early discontinuation (~ 12 weeks in the RA trial and 8 weeks in the PsA and AS trials). Serum samples were collected for laboratory analyses and for the detection of antibodies to golimumab. A highly sensitive, drug-tolerant, enzyme immunoassay was used to detect antibodies to golimumab. Immunogenicity analyses included all golimumab-treated patients who had a baseline sample and at least one post-baseline golimumab infusion.
Adverse events are summarized by treatment group within each study and pooled across the studies for both the placebo-controlled period and open-label follow-up. Due to the differences in the lengths of follow-up between the three IV golimumab trials, time-adjusted incidences of AEs (events per 100 patient-years [100 PY]) with 95% confidence intervals are also provided across indications by treatment groups. Adverse events of interest included serious infections, malignancies, major adverse cardiovascular events (MACE, defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), and infusion reactions.
Arthritis Res Ther. 2022;24(73) © 2022 BioMed Central, Ltd.
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