Summary

• There have been reports of severe hepatic reactions including acute liver failure in patients receiving tumor necrosis factor (TNF) blockers.¹
• In the controlled phase of the GO-FURTHER trial, through week 24, alanine aminotransferase (ALT) elevations ≥5× upper limit of normal (ULN) occurred in 0.8% of SIMPONI ARIA-treated patients and 0% of control-treated patients and ALT elevations ≥3×ULN occurred in 2.3% of SIMPONI ARIA-treated patients and 2.5% of control-treated patients.¹
• In the controlled phase of the GO-VIBRANT trial, through week 24, ALT elevations ≥5×ULN occurred in 1.7% of SIMPONI ARIA-treated patients and <1% of placebo (PBO)-treated patients and ALT elevations ≥3×ULN to <5×ULN occurred in 2.9% of SIMPONI ARIA-treated patients and <1% of PBO-treated patients.¹
• In the integrated safety data from phase 3 clinical studies (GO-FURTHER, GO-VIBRANT, and GO-ALIVE), the safety of SIMPONI ARIA in patients with active rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) was assessed. Patients with ALT ≤ULN at baseline reported ALT elevations ≥5×ULN in 1.2% of patients treated with SIMPONI ARIA.²
• The proportions of patients who received SIMPONI ARIA and intravenous (IV) PBO and developed ALT elevations ≥5×ULN were 2.1% and 0% with methotrexate (MTX), respectively compared to 0.7% and 1.4% without MTX at baseline, respectively.²

PRODUCT LABELING

Adverse Reactions

Clinical Trial Experience

Liver Enzyme Elevations

There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF blockers.¹

In the controlled phase of the GO-FURTHER trial, through week 24, ALT elevations ≥5×ULN occurred in 0.8% of SIMPONI ARIA-treated patients and 0% of control-treated patients and ALT elevations ≥3×ULN occurred in 2.3% of SIMPONI ARIA-treated patients and 2.5% of control-treated patients.¹

In the controlled phase of the GO-VIBRANT trial, through week 24, ALT elevations ≥5×ULN occurred in 1.7% of SIMPONI ARIA-treated patients and <1% of control-treated patients and ALT elevations ≥3×ULN to <5×ULN occurred in 2.9% of SIMPONI ARIA-treated patients and <1% of control-treated patients.¹

Since many of the patients in the phase 3 trial were also taking medications that cause liver enzyme elevations (eg, nonsteroidal anti-inflammatory drugs, MTX, or isoniazid prophylaxis), the relationship between SIMPONI ARIA and liver enzyme elevation is not clear.¹

CLINICAL DATA

Integrated Safety Data From Phase 3 Clinical Studies (GO-FURTHER, GO-VIBRANT, and GO-ALIVE)

• Integrated safety analysis from 3 double-blinded, PBO-controlled, randomized phase 3 clinical studies (GO-FURTHER, GO-VIBRANT, and GO-ALIVE) assessed the safety events across active RA, PsA, and AS in patients treated with SIMPONI ARIA.²
• Patients were randomized to receive SIMPONI ARIA (2 mg/kg) at weeks 0, 4, 12, and 20 or IV PBO. Patients randomized to the PBO group crossed over to the SIMPONI ARIA treatment group at week 24, except for RA patients who met early escape criteria crossed over at week 16 and AS patients who were randomized to the PBO treatment group crossed over at week 16.
• Safety data were analyzed up to week 112 in RA patients and up to week 60 in both PsA and AS patients.

Results

• Overall, 1248 patients were treated with SIMPONI ARIA across active RA, PsA, and AS.
• Patients with ALT ≤ULN at baseline reported ALT elevations ≥5×ULN in 1.2% of patients treated with SIMPONI ARIA.
• The proportions of patients who received SIMPONI ARIA and IV PBO and developed ALT elevations ≥5×ULN were 2.1% and 0% with MTX, respectively compared to 0.7% and 1.4% without MTX at baseline, respectively.

Controlled Trials (IV Administration) - RA

Two randomized, double-blinded, controlled phase 3 clinical studies (GO-LIVE and GO-FURTHER) evaluated the efficacy and safety of SIMPONI ARIA, administered intravenously, in adult patients with moderately to severely active RA despite treatment with MTX.^3,4

• In the GO-LIVE study, SIMPONI ARIA was administered at a dose of 2 mg/kg or 4 mg/kg every 12 weeks with or without concomitant MTX.³
• In the GO-FURTHER study, SIMPONI ARIA was administered at a dose of 2 mg/kg at weeks 0 and 4 and every 8 weeks thereafter with concomitant MTX.⁴

The data described below are based on combined safety results from the GO-LIVE and GO-FURTHER studies. Please note that the safety data presented in the full prescribing information for SIMPONI ARIA are based on clinical trial experience in the GO-FURTHER study only.

Results – PBO-Controlled Portions

• In the PBO-controlled portions of these studies (through week 24), a total of 1012 patients were treated with SIMPONI ARIA and 326 patients were treated with PBO. The average duration of follow-up for these studies was 21.1 weeks for patients in the control group and 22.1 weeks for patients in the SIMPONI ARIA group.⁵
• A summary of maximum postbaseline ALT and aspartate aminotransferase elevations and hepatobiliary adverse events occurring during the PBO-controlled portions (through week 24) of these studies is provided in Table: Summary of Maximum Postbaseline ALT and AST Elevations and Hepatobiliary Adverse Events During PBO-Controlled Portions (Week 24) of Phase 3 Studies in RA.

LITERATURE SEARCH

A literature search of Ovid MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 09 December 2024.