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Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Clinical Studies Experience

The safety data described below are based on 5 pooled, randomized, double-blind, controlled Phase 3 trials in patients with RA, PsA, and AS (Studies RA-1, RA-2, RA-3, PsA, and AS) [see Clinical Studies]. These 5 trials included 639 control-treated patients and 1659 SIMPONI (golimumab injection) -treated patients including 1089 with RA, 292 with PsA, and 278 with AS. The proportion of patients who discontinued treatment due to adverse reactions in the controlled Phase 3 trials through Week 16 in RA, PsA and AS was 2% for SIMPONI (golimumab injection) -treated patients and 3% for placebo-treated patients. The most common adverse reactions leading to discontinuation of SIMPONI (golimumab injection) in the controlled Phase 3 trials through Week 16 were sepsis (0.2%), alanine aminotransferase increased (0.2%), and aspartate aminotransferase increased (0.2%).

The most serious adverse reactions were:

• Serious Infections [see WARNINGS AND PRECAUTIONS]
• Malignancies [see WARNINGS AND PRECAUTIONS]

Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 RA, PsA and AS trials through Week 16, occurring in 7% and 6% of SIMPONI (golimumab injection) -treated patients as compared with 6% and 5% of control-treated patients, respectively.

Infections

In controlled Phase 3 trials through Week 16 in RA, PsA, and AS, infections were observed in 28% of SIMPONI (golimumab injection) -treated patients compared to 25% of control-treated patients [for Serious Infections, see WARNINGS AND PRECAUTIONS].

Liver Enzyme Elevations

There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of SIMPONI (golimumab injection) in patients with RA, PsA, and AS through Week 16, ALT elevations ≥ 5 x ULN occurred in 0.2% of control-treated patients and 0.7% of SIMPONI (golimumab injection) -treated patients and ALT elevations ≥ 3 x ULN occurred in 2% of control­treated patients and 2% of SIMPONI (golimumab injection) -treated patients. Since many of the patients in the Phase 3 trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDs, MTX), the relationship between SIMPONI (golimumab injection) and liver enzyme elevation is not clear.

Autoimmune Disorders and Autoantibodies

The use of TNF-blockers has been associated with the formation of autoantibodies and, rarely, with the development of a lupus-like syndrome. In the controlled Phase 3 trials in patients with RA, PsA, and AS through Week 14, there was no association of SIMPONI (golimumab injection) treatment and the development of newly positive anti-dsDNA antibodies.

Injection Site Reactions

In controlled Phase 3 trials through Week 16 in RA, PsA and AS, 6% of SIMPONI (golimumab injection) -treated patients had injection site reactions compared with 2% of control-treated patients. The majority of the injection site reactions were mild and the most frequent manifestation was injection site erythema. In controlled Phase 2 and 3 trials in RA, PsA, and AS, no patients treated with SIMPONI (golimumab injection) developed anaphylactic reactions.

Psoriasis: New-Onset and Exacerbations

Cases of new onset psoriasis, including pustular psoriasis and palmoplantar psoriasis, have been reported with the use of TNF-blockers, including SIMPONI (golimumab injection) . Cases of exacerbation of preexisting psoriasis have also been reported with the use of TNF-blockers. Many of these patients were taking concomitant immunosuppressants (e.g., MTX, corticosteroids). Some of these patients required hospitalization. Most patients had improvement of their psoriasis following discontinuation of their TNF-blocker. Some patients have had recurrences of the psoriasis when they were re-challenged with a different TNF-blocker. Discontinuation of SIMPONI (golimumab injection) should be considered for severe cases and those that do not improve or that worsen despite topical treatments.

Immunogenicity

Antibodies to SIMPONI (golimumab injection) were detected in 57 (4%) of SIMPONI (golimumab injection) -treated patients across the Phase 3 RA, PsA and AS trials through Week 24. Similar rates were observed in each of the three indications. Patients who received SIMPONI (golimumab injection) with concomitant MTX had a lower proportion of antibodies to SIMPONI (golimumab injection) than patients who received SIMPONI (golimumab injection) without MTX (approximately 2% versus 7%, respectively). Of the patients with a positive antibody response to SIMPONI (golimumab injection) in the Phase 2 and 3 trials, most were determined to have neutralizing antibodies to golimumab as measured by a cell-based functional assay. The small number of patients positive for antibodies to SIMPONI (golimumab injection) limits the ability to draw definitive conclusions regarding the relationship between antibodies to golimumab and clinical efficacy or safety measures.

The data above reflect the percentage of patients whose test results were considered positive for antibodies to SIMPONI (golimumab injection) in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to SIMPONI (golimumab injection) with the incidence of antibodies to other products may be misleading.

Other Adverse Reactions

Table 1 summarizes the adverse drug reactions that occurred at a rate of at least 1% in the combined SIMPONI (golimumab injection) groups during the controlled period of the 5 pooled Phase 3 trials through Week 16 in patients with RA, PsA, and AS.

Table 1: Adverse Drug Reactions Reported by ≥ 1% of Patients in the Phase 3 Trials of RA, PsA, and AS through Week 16^a

Less common clinical trial adverse drug reactions

Adverse drug reactions that occurred < 1% during the SIMPONI (golimumab injection) clinical trials included the following events listed by system organ class:

Nervous system disorders: central nervous system demyelinating disorders (such as multiple sclerosis), peripheral demyelinating polyneuropathy

Methotrexate

For the treatment of RA, SIMPONI (golimumab injection) should be used with methotrexate (MTX) [see Clinical Studies]. Since the presence or absence of concomitant MTX did not appear to influence the efficacy or safety of SIMPONI (golimumab injection) in the treatment of PsA or AS, SIMPONI (golimumab injection) can be used with or without MTX in the treatment of PsA and AS [see Clinical Studies and CLINICAL PHARMACOLOGY].

Biologic Products for RA, PsA, and/or AS

An increased risk of serious infections has been seen in clinical RA studies of other TNF-blockers used in combination with anakinra or abatacept, with no added benefit; therefore, use of SIMPONI (golimumab injection) with abatacept or anakinra is not recommended [see WARNINGS AND PRECAUTIONS]. A higher rate of serious infections has also been observed in RA patients treated with rituximab who received subsequent treatment with a TNF-blocker. There is insufficient information to provide recommendations regarding the concomitant use of SIMPONI (golimumab injection) and other biologic products approved to treat RA, PsA, or AS.

Live Vaccines

Live vaccines should not be given concurrently with SIMPONI [see WARNINGS AND PRECAUTIONS].

Cytochrome P450 Substrates

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα) during chronic inflammation. Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as golimumab, the formation of CYP450 enzymes could be normalized. Upon initiation or discontinuation of SIMPONI (golimumab injection) in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.

Last reviewed on RxList: 8/31/2010
This monograph has been modified to include the generic and brand name in many instances.