SUMMARY

• SIMPONI ARIA is indicated for the treatment of active psoriatic arthritis (PsA) in patients aged ≥2 years.¹
• In pediatric patients with active PsA, the SIMPONI ARIA dosage regimen, based on body surface area (BSA), is 80 mg/m² administered as an intravenous (IV) infusion over 30 minutes at weeks 0 and 4 and every 8 weeks thereafter. Follow The dilution and administration instructions for SIMPONI ARIA.¹
• In adults with active PsA, the SIMPONI ARIA dosage regimen is 2 mg/kg administered as an IV infusion over 30 minutes at weeks 0 and 4 and every 8 weeks thereafter. Follow the dilution and administration instructions for SIMPONI ARIA.¹
• Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with golimumab and other tumor necrosis factor-blocking agents.¹
• The safety and effectiveness in pediatric patients aged <2 years have not been established in active polyarticular juvenile idiopathic arthritis (pJIA) or PsA. The safety and effectiveness of SIMPONI ARIA in pediatric patients with conditions other than pJIA and PsA have not been established.¹
• The efficacy of SIMPONI ARIA in pediatric patients with PsA is based on the pharmacokinetic exposure and extrapolation of the established efficacy of SIMPONI ARIA, as reported in a trial conducted among adult patients with PsA.¹
• In the GO-VIBRANT phase 3, multicenter, randomized, double-blinded, placebo-controlled trial of biologic-naïve adult patients with active PsA, significantly greater proportions of patients receiving SIMPONI ARIA (75.1%) than patients receiving placebo (21.8%) achieved ≥20% improvement in the American College of Rheumatology response criteria (ACR20) at week 14 (P<0.001). Through week 24, ≥1 adverse event (AE) was reported in 46.3% of patients who received SIMPONI ARIA compared to 40.6% of patients who received placebo.²

CLINICAL DATA

Phase 3 Study

Kavanaugh et al (2017)² and Husni et al (2020)³ conducted a phase 3, multicenter, randomized, double-blinded, placebo-controlled trial (GO-VIBRANT) that evaluated the safety and efficacy of biologic-naïve adult patients with active PsA receiving SIMPONI ARIA.

Study Design/Methods

• Eligible patients were biologic-naïve adults (≥18 years) with a diagnosis of PsA for ≥6 months who met the Classification Criteria for Psoriatic Arthritis or who had active PsA (defined as ≥5/66 swollen joints, ≥5/68 tender joints, and a high sensitivity C-reactive protein level of ≥0.6 mg/dL) despite current or previous disease-modifying antirheumatic drug therapy (≥3 months) and/or nonsteroidal anti-inflammatory drug (NSAID) therapy (≥4 weeks) or demonstrated intolerance to these agents at screening.
• Patients were permitted to continue methotrexate (MTX) at a dose of ≤25 mg/week for ≥3 months provided they had been stable for ≥4 weeks, received stable dosing of oral corticosteroids (≤10 mg prednisone/day) for ≥2 weeks, and received concomitant NSAIDs at approved doses if they received stable doses for ≥2 weeks prior to the first SIMPONI ARIA administration.
• Patients were randomized (1:1) to either SIMPONI ARIA 2 mg/kg (n=241) at weeks 0 and 4 and every 8 weeks thereafter or IV placebo (n=239) at weeks 0, 4, 12, and 20, with crossover to SIMPONI ARIA at weeks 24 and 28 and every 8 weeks thereafter through week 52.
• Patients in both treatment groups who had <5% improvement in swollen and tender joint counts were entered into early escape at week 16 and allowed 1 of the following treatment modifications: an increase in corticosteroid dose (total dose: prednisone ≤10 mg/day or equivalent), MTX dose (total dose ≤25 mg/week), or NSAID dose or initiation of an NSAID, corticosteroids (prednisone ≤10 mg/day or equivalent), MTX (≤25 mg/week), sulfasalazine (≤3 g/day), hydroxychloroquine (≤400 mg/day), or leflunomide (≤20 mg/day).
• The primary endpoint was ACR20 response at week 14.
• The major secondary endpoints were a change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI), ≥75% improvement in Psoriasis Area and Severity Index (PASI 75 [only in patients with ≥3% BSA psoriasis skin involvement at baseline]), and ≥50% improvement in the American College of Rheumatology response criteria (ACR50) at week 14 and a change from baseline in the total modified van der Heijde-Sharp (structural damage) score at week 24.
• The controlled secondary endpoints were ≥70% improvement in the American College of Rheumatology response criteria (ACR70), onset of enthesitis, dactylitis, 36-item Short Form Physical Component Summary/Mental Component Summary scores at week 14, and ACR50 at week 24.
• Additional endpoints outside those listed were not adjusted for multiplicity. Nominal P values are provided.
• Efficacy assessments for ACR20, ACR50, ACR70, HAQDI score, PASI 75, ≥90% improvement in Psoriasis Area and Severity Index, and 100% improvement in Psoriasis Area and Severity Index were also conducted through week 52.
• AEs were monitored through week 60 for patients who received ≥1 dose of SIMPONI ARIA.

Results

Patient Characteristics

• Overall, 480 patients were randomized (SIMPONI ARIA: 241; placebo: 239).
• Approximately 52% of patients were male. The mean age was 46 years, and the mean disease duration was 5.8 years.
• At baseline, 70% of all patients were receiving MTX, 27.7% were receiving low-dose oral corticosteroids, and 70.8% were receiving NSAIDs. These were comparable between treatment groups.
• Treatment discontinuation, through week 14, occurred in 4 patients in the SIMPONI ARIA group (including 1 patient who met the exclusion criteria prior to receiving the study agent) and 12 patients in the placebo group.
• Treatment discontinuation, after week 14, occurred in 7 patients in the SIMPONI ARIA group and 5 patients in the placebo group through week 24.
• After week 24 and through week 52, treatment discontinuation occurred in 17 patients in the SIMPONI ARIA group and 8 patients in the placebo to SIMPONI ARIA crossover group.
• At week 16, 2 patients in the SIMPONI ARIA group and 49 patients in the placebo group met the early escape criteria.

Efficacy

• The study met its primary and major secondary endpoints.
• At week 2, significantly greater proportions of patients receiving SIMPONI ARIA (45.6%) than patients receiving placebo (7.5%) achieved ACR20 (P<0.001).
• At week 14 (primary endpoint), significantly greater proportions of patients receiving SIMPONI ARIA (75.1%) than patients receiving placebo (21.8%) achieved ACR20 (P<0.001).
• At week 14, 27.0% of patients receiving SIMPONI ARIA and 4.2% of patients receiving placebo achieved minimal disease activity.
• The proportions of ACR responders in the placebo to SIMPONI ARIA crossover group approached those in the SIMPONI ARIA treatment group at week 28.
• Results at weeks 14, 24, and 52 are provided in Table: Summary of Clinical Efficacy at Week 14, Week 24, and Week 52.

Safety

• Through week 24, ≥1 AE was reported in 46.3% of patients receiving SIMPONI ARIA and 40.6% of patients receiving placebo. In comparison to 8 patients (3.3%) receiving placebo, 7 patients (2.9%) receiving SIMPONI ARIA reported ≥1 serious adverse event (SAE) and included pleomorphic adenoma, myocardial infarction, pneumonia, abnormal liver function test, neuritis, drug-induced liver injury (MTX-induced toxic hepatitis), and pustular psoriasis.
• Through week 60, ≥1 AE and ≥1 SAE were reported in 50.9% and 5.2% of patients, respectively.
• Two deaths and 2 malignancies were reported in the placebo group through week 24 and 1 death (acute hepatitis of mixed etiology) and 2 malignancies (gastric cancer in the placebo to SIMPONI ARIA crossover group, colon cancer in the SIMPONI ARIA group) were reported through week 60.
• Through week 24, 1 demyelinating event diagnosed as noninfective encephalomyelitis was reported in the SIMPONI ARIA group (hospitalization was not required, but the study drug was discontinued).
• The most common treatment-emergent adverse reaction through week 24 was infection, which was reported in 18.8% and 15.5% of patients in the SIMPONI ARIA and placebo treatment groups, respectively.
• The most common AE through week 60 was infection, which was reported in 22.8% of patients in the SIMPONI ARIA group.
• No opportunistic infections were reported through week 60; however, active tuberculosis was reported in 2 patients treated with SIMPONI ARIA.
• Infusion reactions occurred in 4 patients (0.9%) who received SIMPONI ARIA through week 52. None of the infusion reactions were considered serious or severe.
• The proportion of patients who tested positive for antibodies to golimumab through week 20 was 19.5% (n=44). Of those, 16 patients were positive for neutralizing antibodies.
• Through week 52, the proportion of patients who tested positive for antibodies to golimumab was 22% (53/230 [23%] in the SIMPONI ARIA group and 46/220 [21%] in the placebo to SIMPONI ARIA crossover group). The incidence of antibodies to golimumab was noted to be higher in patients treated without MTX at baseline vs those treated with MTX at baseline (39/134 [29%] vs 60/316 [19%]), with no difference in the incidence of neutralizing antibodies (35.9% vs 36.7%).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 08 August 2024.