SUMMARY  

• A phase 3 study was conducted to evaluate the efficacy and safety of SIMPONI ARIA, with and without methotrexate (MTX), in biologic-naïve adult patients with active psoriatic arthritis (PsA).^1,2

CLINICAL DATA

Phase 3 Study

Kavanaugh et al (2017)¹ and Husni et al (2020)² evaluated the safety and efficacy of SIMPONI ARIA in biologic-naive adult patients with active psoriatic arthritis in a double-blind, randomized, multicenter, placebo controlled, phase 3 study (GO-VIBRANT).

Study Design Methods

• Eligible patients were biologic-naïve adults (≥18 years) with a diagnosis of PsA for ≥6 months and met Classification Criteria for Psoriatic Arthritis (CASPAR), had active PsA (defined as ≥5/66 swollen joints, ≥5/68 tender joints, and had a high sensitivity C-reactive protein [CRP] level ≥0.6mg/dL) despite current of previous DMARD (≥3 months) and/or NSAID therapy (≥4 weeks) or demonstrated intolerance to these agents at screening.  
• Patients receiving MTX for ≥3 months were permitted to continue at a dose of ≤25 mg/week provided their MTX dose remained stable for ≥4 months.
• Patients were permitted to receive concomitant NSAIDs at approved doses or concomitant oral corticosteroids if they had been receiving a stable dose for ≥2 weeks prior to the first SIMPONI ARIA administration.    
• Patients were randomized to receive SIMPONI ARIA 2 mg/kg (n=241) at weeks 0, 4, and every 8 weeks thereafter, or intravenous placebo (n=239) at weeks 0, 4, 12 and 20, with crossover to SIMPONI ARIA at week 24 through week 52.  
• Randomization of patients into treatment groups were stratified by geographic region and baseline MTX (yes or no).  
• Patients in both treatment groups who had <5% improvement in swollen and tender joint counts entered early escape at week 16.  Subjects qualifying for early escape were allowed 1 of the following treatment modifications: an increase in MTX dose (≤25 mg/week), corticosteroid dose (prednisone ≤10 mg/day, or equivalent), or NSAID dose; or initiation of NSAIDs, corticosteroids (prednisone ≤10mg/day or equivalent), MTX (≤25 mg/week), sulfasalazine (≤3 g/day), hydroxychloroquine (≤400 mg/day), or leflunomide (≤20 mg/day).  
• The primary endpoint was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR) criteria (ACR20) at week 14.  
• Major secondary endpoints included the proportion of patients who achieved 75% improvement from baseline in psoriasis area and severity index (PASI) score, ACR 50 response at week 14, and change from baseline in total PsA-modified van der Heijde-Sharp (vdH-S) score at week 24.
• Efficacy was assessed through week 52 and adverse events (AEs) were monitored through week 60.

Results

• A total of 480 patients were randomized (SIMPONI ARIA: 241; placebo: 239).
• 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 the treatment groups.  
• At week 14, 75.1% of patients in the SIMPONI ARIA group achieved an ACR20 response vs 21.8% in the placebo group (primary endpoint, P<0.001).
• Results at weeks 14, 24, and 52 are provided in the Table: Summary of Efficacy by Methotrexate Utilization at Weeks 14, 24 and 52.

Safety

• Through week 24, ≥1 AE was reported in 46.3% of patients receiving SIMPONI ARIA and 40.6% of patients receiving placebo. A total of 7 (2.9%) patients receiving SIMPONI ARIA reported >1 serious adverse event (SAE) which included pleomorphic adenoma, myocardial infarction, pneumonia, abnormal liver function test, neuritis, drug-induced liver injury (MTX-induced toxic hepatitis), and pustular psoriasis in comparison to 8 (3.3%) patients receiving placebo.
• Two deaths and 2 malignancies were reported in the placebo group through week 24 and 1 death (acute hepatitis) and 2 malignancies (gastric cancer, colon cancer) were reported in patients treated with SIMPONI ARIA through week 60.
• 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.
• Through week 60, ≥1 AE and ≥1 SAE was reported in 50.9% and 5.2%, respectively of patients who received ≥1 administration of SIMPONI ARIA.
• Through week 60, the most common treatment-emergent adverse reaction was infection, which was reported in 22.8% of all SIMPONI ARIA treated patients.
• Through week 60, infusion reactions were reported in 4 (0.9%) SIMPONI ARIA treated patients. None of the events were considered serious or severe.
• Through week 60, 157 (39.1%) patients out of the 401 patients developed postbaseline ALT level > ULN. Most of the events were considered mild and transient.

LIterature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 05 August 2024.