Summary

• The safety and efficacy of SIMPONI ARIA were evaluated for the treatment of patients with active ankylosing spondylitis (AS) in the phase 3 GO-ALIVE study.^1,2
  • At week 16, treatment with SIMPONI ARIA resulted in a significantly greater proportion of patients who achieved ≥20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) compared to patients receiving placebo (primary endpoint; 73.3% vs 26.2%, respectively; P≤0.001).¹
  • Improvement in health-related quality of life (HRQoL) outcomes, including the physical and mental component summary (PCS/MCS) scores of the Medical Outcomes Study Short Form-36 questionnaire (SF-36) and the Ankylosing Spondylitis Quality of Life (ASQoL), were significantly greater for patients in the SIMPONI ARIA group compared with placebo at week 16. These improvements were observed through week 52.²
  • Through week 16, 32.4% of patients receiving SIMPONI ARIA and 23.3% of patients receiving placebo experienced ≥1 adverse event (AE).¹
  • Through week 60, 55.4% of patients experienced ≥1 AE.²

CLINICAL DATA

Phase 3 - GO-ALIVE

Deodhar et al (2018)¹ and Reveille et al (2019)² evaluated the efficacy and safety of SIMPONI ARIA in adult patients with active AS in a randomized, double-blind, placebo-controlled, phase 3 study (GO-ALIVE).

Study Design/Methods

• A total of 208 patients were randomized (1:1) to SIMPONI ARIA 2 mg/kg at weeks 0, 4, 12 and every 8 weeks thereafter, or placebo (PBO) at weeks 0, 4, and 12, with crossover to SIMPONI ARIA 2 mg/kg at weeks 16 and 20 and every 8 weeks thereafter.
• Eligible patients were adults with a diagnosis of AS (per modified New York criteria) for at least 3 months, with symptoms of active disease (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥4, a visual analog scale score for total back pain of ≥4), and C-reactive protein (CRP) ≥0.3 mg/dL and either an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs (NSAID).
• Up to 20% of patients with prior anti-tumor necrosis factor (TNF) therapy (excluding SIMPONI ARIA) and 10% of patients with complete ankylosing of the spine were included.
• At stable doses, concomitant use of methotrexate (≤25 mg/week), sulfasalazine, hydroxychloroquine, NSAID, other analgesics, and low-dose oral corticosteroids (dose equivalent to ≤10 mg prednisone/day) was permitted.
• The primary endpoint was ASAS20 response at week 16.
• Major secondary endpoints included ASAS40 response, ≥50% improvement in BASDAI (BASDAI50 response) and change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), all at week 16.
• Additional efficacy assessments included ASAS20/40, BASDAI50/70, and change in BASFI, Bath Ankylosing Spondylitis Metrology Index (BASMI), and enthesitis (University of California, San Francisco [UCSF] index) scores at week 52.²
• HRQoL outcomes were assessed at week 16 and week 52 using the SF-36 PCS/MCS and the ASQoL questionnaires.
• Safety was monitored through week 60.

Results

Patient Characteristics

• A total of 208 patients were randomized to receive PBO (n=103) or SIMPONI ARIA 2 mg/kg (n=105).¹
• Baseline demographics and disease characteristics were generally comparable between groups.
• The majority of patients were male (78%). The mean age was 39 years with mean disease duration of 5.5 years.
• The proportions of patients who were HLA-B27 positive, had complete ankylosis of the spine were 89.9%, and 5.8%, respectively. A total of 30 patients had been previously treated with 1 anti-TNF agent in the PBO (n=14) and SIMPONI ARIA (n=16) treatment groups.
• A total of 17 patients (placebo, n=4; placebo→SIMPONI ARIA, n=5; SIMPONI ARIA, n=8) discontinued study agent through week 60.²

Efficacy

• The results of the primary endpoint, major secondary endpoints and a few other efficacy endpoints at week 16 can be found in Table: Summary of Efficacy Results at Week 16.¹
• There was a significantly greater proportion of SIMPONI ARIA-treated patients with an ASAS20 response at week 2 compared with placebo (37.1% vs. 19.4%; p=0.005). Among patients in the SIMPONI ARIA group, after week 16 the proportion of patients achieving ASAS20 and ASAS40 response were maintained through week 28.
• The results of other efficacy assessments at week 52 can be found in Table: Summary of Efficacy Results at Week 52.²

Health-Related Quality of Life

• Improvement in HRQoL, including SF-36 PCS and MCS scores and ASQoL, were significantly greater for patients in the SIMPONI ARIA group compared with placebo at week 16 and were maintained through week 52.
• The results of HRQoL outcomes at week 16 are summarized in Table: Health-Related Quality of Life at Week 16.¹
• The results of HRQoL outcomes from week 16 to week 52 are summarized in Table: Health-Related Quality of Life Outcomes at Week 52.²

Safety

• Through week 16:¹
  • A total of 32.4% of patients receiving SIMPONI ARIA and 23.3% of patients receiving placebo experienced ≥1 AE.
  • The most common AE reported was infection (11.4%, SIMPONI ARIA; 7.8%, placebo) with nasopharyngitis and upper respiratory tract infection being the most frequent.
  • Serious adverse events (SAEs) were reported in 2 patients in the SIMPONI ARIA group including pneumonia (n=1), and pancreatitis (n=1).
  • Three patients in the SIMPONI ARIA group (2.9%) experienced an infusion-related reaction, none of which were serious or severe.  Additionally, 3 patients in the PBO group reported eye disorders (n=1, eye pain with no previous history; and 2 patients with previous uveitis history that wasn't occurring at the trial start [n=1, iritis; n=1, uveitis]).
• Through week 28:¹
  • A total of 34.8% of all SIMPONI ARIA treated patients (all patients in the SIMPONI ARIA group and all patients in the PBO group who received ≥1 infusion of SIMPONI ARIA) experienced ≥1 AE, of which infections were the most common (17.2%).
  • There were no reports of new or worsening of inflammatory bowel disease, depression, demyelination, opportunistic infections, malignancies, or deaths through week 28.
  • Between weeks 16 and 28, no additional infusion-related reactions or SAEs were reported.
  • After administration of SIMPONI ARIA 2 mg/kg at weeks 0, 4, and every 8 weeks, median trough serum golimumab concentration reached steady state by Week 12 and was maintained at Week 20 (0.65 μg/ml).
    • Among SIMPONI ARIA-treated patients, 20 tested positive for antibodies to golimumab using a highly sensitive, drug-tolerant immunoassay (6 were positive for neutralizing antibodies).
    • No infusion reactions occurred in these patients who tested positive and median trough concentrations tended to be lower in these patients.
• Through week 60:²
  • A total of 204 patients received ≥1 administration of SIMPONI ARIA.
  • A total of 55.4% of patients experienced ≥1 AE, including 3.4% who experienced an SAE.
  • The most common AE reported was infection (32.8%).
  • One patient who screened negative for tuberculosis (TB) was diagnosed with pulmonary TB.
  • There were no reports of opportunistic infections, malignancies, or deaths.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 16 January 2025.

Summarized in this response are relevant data form the pivotal phase 3 controlled clinical trial.