Abstract and Introduction
Background: Intravenous (IV) golimumab, a TNFi, is approved for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We analyzed pooled safety results from three phase 3 IV golimumab trials in these rheumatologic diseases and hypothesized that the safety profile of IV golimumab would be similar to that established for other TNFi, including subcutaneous golimumab.
Methods: Data from three double-blind, randomized trials of IV golimumab in patients with RA, PsA, and AS, each with a placebo-controlled period and an extension of active treatment, were included. Golimumab 2 mg/kg was administered at weeks 0 and 4, then every 8 weeks through week 100 (RA) or week 52 (PsA, AS). Concomitant low-dose, oral corticosteroids were permitted. Concomitant methotrexate was required in the RA trial and permitted in the PsA and AS trials; placebo patients crossed over to golimumab at weeks 24 (RA, PsA) and 16 (AS), respectively. Adverse events (AEs), including infections, serious infections, malignancies, and major adverse cardiovascular events (MACE), were assessed through week 112 (RA) or week 60 (PsA, AS).
Results: In total, 539 patients were randomized to placebo, and 740 patients were randomized to golimumab; 1248 patients received ≥ 1 golimumab administration. Among the placebo and golimumab patients, respectively, during the placebo-controlled periods, 40.6% and 50.3% had an AE, 2.4% and 3.8% had a serious AE, and 0.4% and 0.8% had a serious infection. Among all golimumab-treated patients, the numbers of events/100 patient-years (95% CI) were as follows: AEs, 175.2 (169.0, 181.6); serious AEs, 12.7 (11.0, 14.5); serious infections, 3.4 (2.5, 4.4); active tuberculosis, 0.4 (0.1, 0.8); opportunistic infection, 0.2 (0.1, 0.6); malignancies, 0.4 (0.2, 0.9), and MACE, 0.5 (0.2, 1.0). There were no cases of lymphoma. Three (0.6%) placebo-treated patients and 6 (0.5%) golimumab-treated patients died during the studies. Concomitant methotrexate was associated with increased occurrence of elevated alanine transaminase levels and lower incidence of antibodies to golimumab. During the placebo-controlled periods, serious infections in the placebo and golimumab groups were more common in patients receiving concomitant low-dose oral corticosteroids vs. those not receiving corticosteroids.
Conclusions: IV golimumab demonstrated a safety profile that was broadly consistent across these rheumatologic indications and with other TNFi, including subcutaneous golimumab. Concomitant methotrexate or corticosteroids were associated with an increase in specific AEs.
Trial registrations: ClinicalTrials.gov, NCT00973479. Registered on September 9, 2009. ClinicalTrials.gov, NCT02181673. Registered on July 4, 2014. ClinicalTrials.gov, NCT02186873. Registered on July 10, 2014.
Golimumab is a human monoclonal antibody that binds and inhibits the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Intravenous (IV) golimumab is approved for the treatment of rheumatoid arthritis (RA) (in combination with methotrexate [MTX]), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Efficacy and safety of IV golimumab have been assessed in three double-blind, randomized, placebo-controlled, phase 3 trials of patients with RA (GO-FURTHER),[2–4] PsA (GO-VIBRANT),[5,6] and AS (GO-ALIVE).[7,8] Patients with immune-mediated diseases such as RA, PsA, and AS are likely to require ongoing treatment. Thus, the long-term safety of treatments for these conditions is of particular interest for both health care providers and patients. Possible associations with the risk of serious infections, opportunistic infections, tuberculosis (TB), demyelinating disorders, and lymphoma have been reported for other TNF inhibitors (TNFi).[9–14]
Intravenous golimumab has demonstrated significantly greater improvements, compared with placebo, in signs and symptoms in patients with RA, PsA,[5,15] and AS. In addition, IV golimumab treatment has slowed radiographic progression compared with placebo in patients with RA and PsA.[3,15] Trial extensions of active treatment with golimumab demonstrated that improvements were maintained over time.[4,6,8]
Here, we report pooled safety results from the three double-blind, randomized, placebo-controlled, phase 3 trials of IV golimumab in patients with RA,[2–4] PsA,[5,6] and AS,[7,8] each with a placebo-controlled period and an extension of active treatment with golimumab (Figure 1). Safety results are presented for all treated patients, as well as for patient subgroups defined by baseline use of MTX and low-dose oral corticosteroids.
Study designs of three phase 3 trials of golimumab in patients with a rheumatoid arthritis (GO-FURTHER), b psoriatic arthritis (GO-VIBRANT), and c ankylosing spondylitis (GO-ALIVE)
Arthritis Res Ther. 2022;24(73) © 2022 BioMed Central, Ltd.
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