SUMMARY

• GO-VIVA is a multicenter, single-arm, open-label study that evaluated the efficacy and safety of SIMPONI ARIA in pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) despite methotrexate (MTX) treatment. Pharmacokinetics (PK), efficacy and safety results were presented at week 28 and week 52.^1-3
• Long-term extension data from (LTE) GO-VIVA including PK, efficacy, immunogenicity, and safety results were assessed over 252 weeks.⁴

CLINICAL DATA

GO-VIVA Study – Results through Week 52

Ruperto et al (2019)¹, Ruperto et al (2021)² and Leu et al (2019)³ evaluated the PK, efficacy and safety of SIMPONI ARIA in pediatric patients with active pJIA despite MTX treatment in a multicenter, single-arm, open-label, phase 3 study. Active pJIA was defined as one of the following per Juvenile Idiopathic Arthritis (JIA) International League of Associations of Rheumatology (ILAR): extended oligoarticular JIA, RF-positive or RF-negative pJIA, systemic JIA with no systemic symptoms for ≥3 months, enthesitis-related arthritis or polyarticular juvenile psoriatic arthritis (PsA).

Study Design/Methods

• Pediatric patients aged 2 to <18 years weighing >15 kg at screening and enrollment, with a ≥3 month history of pJIA and active arthritis (≥5 active joints) despite MTX (≥10 mg/m²) therapy for ≥2 months prior to screening, and onset of disease before age 16 were enrolled in the study.²
• Patients who were on stable doses of glucocorticoids or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 2 weeks prior to the administration of SIMPONI ARIA or screening, could be enrolled in the study.²
• Any patient who was previously treated with a biologic disease-modifying antirheumatic drug (DMARD) or small molecule therapeutic observed specific washout period.²
• Patients were administered SIMPONI ARIA based on body surface area (BSA); 80 mg/m² was given as an intravenous (IV) infusion (maximum single dose of 240 mg) over 30 minutes at weeks 0 and 4, and every 8 weeks (q8w) thereafter through week 52.²
• Through week 28, patients received the same BSA-based MTX weekly dose as at baseline.²
• After week 28, MTX, other DMARDs, glucocorticoids and NSAIDs could be changed or be added to patients’ regimen.²
• Using a validated, specific, and sensitive method, serum SIMPONI ARIA concentrations were measured at weeks 0, 4, 8, 12, 20, 28, and 52.²
• The primary endpoints were the golimumab trough concentrations and model-predicted steady-state area under the curve (AUC_ss) over an 8-week dosing interval at week 28. This data can be found below under GO-VIVA Study – PK at Week 28 and 52.²
• Efficacy assessments included JIA core set of measures which included physician global assessment of the overall disease activity, number of joints with active arthritis, number of joints with limited range of motion, the cross-culturally adapted and validated version of the Childhood Health Assessment Questionnaire (CHAQ), C-reactive protein (CRP), and morning sickness duration.²
• The efficacy endpoints included:
  • JIA ACR 30, 50, 70, and 90 responses defined as 30%, 50%, 70%, or 90% improvement from baseline according to the American College of Rheumatology (ACR).²
  • Modified JIA ACR inactive disease defined as no joints with active arthritis and no active uveitis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributed to JIA; normal CRP; medical doctor (MD) global ≤5 mm; and duration of morning stiffness of <15 min.²
  • Clinical remission during treatment defined as inactive disease at each visit for ≥6 months while on treatment.²
  • Juvenile Arthritis Disease Activity Score 71 (JADAS 71):²
    • High disease activity: >10.5
    • Moderate disease activity: 3.9-10.5
    • Low disease activity: 1.1-3.8
    • Inactive disease: ≤1
• Safety assessments were performed at every visit which also included routine laboratory evaluations.²
• Antibodies to SIMPONI ARIA was also evaluated in serum samples collected at weeks 0, 4, 8, 12, 28, and 52.²
• The results described below are from the full analysis set (FAS) which included all patients who received at least 1 dose of SIMPONI ARIA.²
• For the analysis of binary composite efficacy endpoints, imputation rules (nonresponder imputation [NRI] for missing data and last observation carried forward [LOCF] for missing components) were used for imputing missing data as per the intention-to-treat principle.²

Results

Patient Characteristics

• A total of 180 patients were screened for the study, of which 130 patients were enrolled and 127 patients were treated. A total of 113 patients remained in the study at week 52.²
• A summary of baseline demographics and disease characteristics is presented in Table: Key Baseline Demographics and Disease Characteristics.

Pharmacokinetics

• At week 28, the IV golimumab 80 mg/m² BSA-based dosing regimen resulted in observed C_trough,ss and AUC_ss that were similar across the pJIA age groups of 2 to <6, 6 to <12, and 12 to <18 years of age. PK exposures were maintained through week 52 (Table: Median PK of Serum Golimumab at Weeks 28 and 52).³

Efficacy

• Improvements from baseline in JIA efficacy measures were observed starting at week 4 and were maintained through week 28 and at week 52.² Efficacy results are presented in Table: Summary of Efficacy Results at Weeks 4, 28, and 52 (N=127).
• Clinical remission during treatment was achieved in 2% of patients at week 28 and 13% of patients at week 52.²

Safety

Results through Week 28¹

• Through week 28, the proportion of patients who experienced at least 1 treatment emergent adverse event (AE) was 77.2%.
• The highest incidence of AEs were infections and infestations (57.5%). The most commonly reported AEs were upper respiratory tract infection (17.3%) and nasopharyngitis (15.0%).
• Through week 28, 6 patients experienced serious AEs which included herpes zoster disseminated, infective exacerbation of bronchiectasis, sepsis, varicella, mycosis fungoides, and suicidal ideation.
• All serious AEs except for varicella resulted in study discontinuation.

Results through Week 52²

• Through week 52, the proportion of patients who experienced at least 1 AE was 85% (108/127). See Table: Summary of AEs through Week 52.
• The highest incidence of AEs reported in 85 patients (66.9%) were infections and infestations (66.9%).
• Through week 52, 9 patients experienced serious AEs which included herpes zoster disseminated, infective exacerbation of bronchiectasis, sepsis, varicella, mycosis fungoides, suicidal ideation, cellulitis, pneumonia, and streptococcal pneumonia and pleural effusion (streptococcal pneumonia and pleural effusion were reported in the same patient).
• All serious AEs except for varicella, cellulitis, and pneumonia resulted in study discontinuation.

GO-VIVA Study – LTE through Week 252

Ruperto et al (2023)⁴ evaluated the PK, efficacy, immunogenicity, and safety of SIMPONI ARIA in pediatric patients who were part of the GO-VIVA trial and continued into the LTE through week 252.

Study Design/Methods

• Patients who continued SIMPONI ARIA 80 mg/m² q8w (maximum single dose 240 mg) after week 52 were included.
• All patients received SIMPONI ARIA 80 mg/m² at weeks 0 and 4, and q8w thereafter through week 244. They received commercial MTX at least through week 28 at the same BSA-based weekly dose as at the time of study entry.
• PK and immunogenicity were assessed through week 244, and safety was assessed through week 252.
• Efficacy measures included the following:
  • JIA ACR 30/50/70/90 response from week 0
  • Clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS-10)
  • Minimal disease activity (MDA)
  • Inactive disease (ID)
  • Remission (>6 continuous months of cJADAS-10-ID)

Results

Patient Characteristics

• Of the 127 patients treated with SIMPONI ARIA, 88.2% (112/127) continued into the LTE and 54.3% (69/127) completed the LTE at week 252. AEs were the most common reason for discontinuation.

Pharmacokinetics

• The observed median golimumab C_trough,ss at weeks 52, 100, 148, 196, and 244 was 0.44, 0.29, 0.29, 0.36, and 0.61 µg/mL, respectively.
• The median golimumab C_trough,ss at week 244 was similar across subgroups by age (26 years, 6-12 years, and 12-18 years) and baseline bodyweight
  (<29.2 kg, 29.2 to <42.4 kg, 42.4 kg to <57 kg, and ≥57 kg).

Efficacy

• The majority of patients with pJIA treated with SIMPONI ARIA achieved JIA ACR 30/50/70/90 response, with overall response rates maintained through week 116.
• The mean cJADAS-10 score decreased from 19.84 (high disease activity) at week 0 to 3.55 (MDA) at week 116 of SIMPONI ARIA.
• Among patients with pJIA treated with SIMPONI ARIA, up to 60% achieved MDA (cJADAS-10 ≤5) through week 116 and >40% achieved ID (cJADAS-10 ≤2.5). Nearly one-third of the patients with pJIA treated with SIMPONI ARIA achieved clinical remission (cJADAS-10 ≤2.5 FOR >24 weeks), with overall rates maintained through week 116.

Immunogenicity

• The antibodies produced (generally low titer) to golimumab were detected with a drug-tolerant method and is summarized in Table: Summary of Golimumab Antibody Status through Weeks 52 and 252.

Safety

• For safety through week 252, please see Table: Treatment-Emergent AEs through Weeks 252.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 22 May 2024.