Summary

• The company cannot recommend any practices, procedures or usage that deviate from the approved labeling.
• A long-term extension (LTE) of a phase 3 clinical trial evaluated the efficacy and safety of SC golimumab in patients with moderately to severely active rheumatoid arthritis (RA) despite methotrexate (MTX) who had previously received IV golimumab.^1,2
  • At week 48 (primary study), the proportion of patients who achieved ≥50% improvement in the American College of Rheumatology criteria (ACR50) was 28%, 11%, and 8% in the IV golimumab + MTX group, IV golimumab monotherapy group, and the placebo + MTX group, respectively.
  • Of the patients who entered the LTE (n=505), the proportion of patients treated with SC golimumab ± MTX who achieved an ACR50 response increased to 44% at LTE weeks 14 and 24.
  • From week 0 of the main study through LTE week 0, the proportion of patients who developed ≥1 adverse event was 83.8%, 79.1%, and 72.1% in the IV golimumab + MTX group, IV golimumab monotherapy group, and the placebo + MTX group, respectively. From LTE week 0 through LTE week 40, at least 1 adverse event was observed in 68.3% and 66.7% of patients receiving SC golimumab 50 mg + MTX and SC golimumab 50 mg monotherapy, respectively.

CLINICAL DATA

Controlled Phase 3 Trial — GO-LIVE

Kremer et al (2010)^1,2 assessed the efficacy and safety of IV golimumab in patients with active RA despite treatment with MTX in a phase 3, randomized, double-blind, multicenter, placebo-controlled study. Active RA was defined as ≥4 tender and ≥4 swollen joints, plus at least 2 of the following: 1) C-reactive protein (CRP) ≥1.5 mg/dL or erythrocyte sedimentation rate (ESR) ≥28 mm/hour, 2) morning stiffness ≥30 minutes, 3) bone erosions, or 4) rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) positivity. Further, patients had to be treated with MTX for ≥3 months before screening, including treatment at a stable dose (15-25 mg/week) for ≥4 weeks.

Study Design/Methods

• A total of 643 adult RA patients were randomized to IV golimumab 2 mg/kg + MTX (n=129), IV golimumab 2 mg/kg (n=128), IV golimumab 4 mg/kg + MTX (n=128), IV golimumab 4 mg/kg (n=129), or IV infusions of placebo + MTX (n=129) every 12 weeks through week 48. IV infusions were administered over a period of 30 minutes (acceptable window for infusion of 25-35 minutes) at weeks 0, 12, 24, 36, and 48.
• Patients were permitted to continue stable doses of oral corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs). Previous but not current anti-tumor necrosis factor (TNF) therapy was also permitted (limited to 20% of the study population) with appropriate washout (REMICADE washout period ≥3 months; etanercept or adalimumab washout period ≥2 months).
• Patients who had <20% improvement from baseline in both swollen and tender joint counts were eligible to enter early escape at week 16 or have a dose regimen adjustment at week 24 in a blinded manner.
• Patients who completed the week 48 infusion were eligible to continue in an open-label LTE with SC golimumab 50 mg subcutaneously every 4 weeks for an additional 24 weeks (LTE weeks 0-24) beginning 12 weeks after the last IV infusion.  Patients were followed for an additional 16 weeks for safety evaluations (LTE weeks 24-40).
• Patients who were treated with placebo + MTX through week 48 of the primary study and had a total tender and swollen joint count ≤3 were discontinued.
• Patients treated with concomitant MTX through week 48 of the primary study continued receiving the same dose.  At the investigator’s discretion, patients were allowed to add, discontinue, or adjust the dose of MTX starting at LTE week 14.
• The primary endpoint of the study was the proportion of patients achieving an ACR50 at week 14. Endpoints assessed in the LTE included 20% improvement according to the American College of Rheumatology criteria (ACR20)/ACR50/70% improvement according to the American College of Rheumatology criteria (ACR70) responses, Disease Activity Score in 28 joints using CRP (DAS28-CRP) moderate/good responses, DAS28-CRP score <2.6, and Health Assessment Questionnaire (HAQ) improvement ≥0.3 units.

Results

Patient Characteristics

• The baseline characteristics of the patients who entered the LTE were consistent with the overall study population and consistent with a diagnosis of moderate to severe RA.
• A total of 565 patients completed the primary study.  Of these, 508 entered the LTE.  A majority (91%; 461/508) of these patients completed the study through LTE week 40.

Efficacy

• The difference observed in the percentage of patients achieving an ACR50 response at week 14 (primary study) for the combined IV golimumab + MTX groups (21.4%) vs placebo + MTX group (13.2%) was not statistically significant (P=0.051).
• A summary of efficacy findings through LTE week 24, including results at week 48 of the primary study, are presented in Table: Summary of Efficacy Results Through LTE Week 24.
• At LTE weeks 14 and 24, the highest ACR response, DAS28-CRP response, and DAS28-CRP score <2.6 response rates were generally noted in patients who were originally randomized to the IV golimumab 4 mg/kg + MTX group.

• Maintenance of ACR and DAS28-CRP responses with SC golimumab was observed among patients who were responders with IV golimumab at LTE week 0. Among patients who were ACR and DAS28-CRP nonresponders with IV golimumab, approximately 20%-50% achieved an ACR response and 35%-82% achieved a DAS28-CRP response with SC golimumab.
• Patients who did not enter early escape or have a dose regimen adjustment during the primary study also had maintenance of ACR responses with SC golimumab.

Safety

• A summary of the safety results through the end of IV golimumab dosing in the primary study and during the LTE enrollment period and throughout the LTE of SC golimumab is presented in Table: Summary of Safety Through LTE Week 40.
• Through LTE week 40, the most commonly reported adverse events were infections across all treatment groups. Upper respiratory tract infection, nasopharyngitis, and bronchitis were the most common infections.  
• A total of 2 patients developed tuberculosis (TB) between weeks 24 and 48 of the primary study.  No additional cases of TB were reported in the LTE.
• There were no reported cases of anaphylaxis or serum sickness during the study.
• In the primary study (through week 48), a total of 3 deaths were reported (1 case each in the IV golimumab 2 mg/kg, 4 mg/kg, and 4 mg/kg + MTX group) due to myocardial infarction, including acute cardiac dysfunction in 1 patient.  After week 48, 3 additional patients receiving IV golimumab died: 1 patient in the 2 mg/kg group (unknown cause), 1 patient in the 2 mg/kg + MTX group (septic shock), and 1 patient in the 4 mg/kg group (respiratory insufficiency following admission for presumptive lung cancer and brain metastases).  Two additional patients died after starting SC golimumab 50 mg + MTX: 1 due to a severe respiratory infection and 1 due to septicemia.
• Through the primary study and the LTE enrollment period, neoplasms were reported in 2 patients (1.6%) receiving placebo + MTX, 3 patients (1.2%) receiving IV golimumab monotherapy, and 17 patients (3.6%) receiving IV golimumab + MTX.  Two patients developed lung neoplasm (both treated with IV golimumab 4 mg/kg + MTX) and 2 developed melanocytic nevus (1 each in the IV golimumab 2 and 4 mg/kg + MTX group).  All other neoplasms developed in 1 patient each.  During the LTE, neoplasms were reported in 2 patients (0.5%).  There were no reported cases of lymphoma.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 13 June 2023.