Indications for SIMPONI^® (golimumab)

SIMPONI^® is a tumor necrosis factor (TNF) blocker indicated for the treatment of:

• Moderately to severely active Rheumatoid Arthritis (RA) in adults, in combination with methotrexate
• Active Psoriatic Arthritis (PsA) in adults, alone or in combination with methotrexate
• Active Ankylosing Spondylitis (AS) in adults

Important Safety Information for SIMPONI^® (golimumab)

SERIOUS INFECTIONS

Patients treated with SIMPONI^® (golimumab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue SIMPONI^® if a patient develops a serious infection.

Reported infections with TNF blockers, of which SIMPONI^® is a member, include:

• Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before SIMPONI^® use and during therapy. Treatment for latent infection should be initiated prior to SIMPONI^® use.
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
• Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with SIMPONI^® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Do not start SIMPONI^® in patients with clinically important active infections, including localized infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with SIMPONI^®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Risk of infection may be higher in patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. Other serious infections observed in patients treated with SIMPONI^® included sepsis, pneumonia, cellulitis, abscess and hepatitis B infection.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers of which SIMPONI^® is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children or adolescents. Malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

In the controlled portions of clinical trials of all TNF‑blocking agents including SIMPONI^®, more cases of lymphoma have been observed among patients receiving TNF‑blocking treatment compared with control patients. In clinical trials, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI: 0.03, 0.77) in the combined SIMPONI^® group compared with an incidence of 0 (95% CI: 0, 0.96) in the placebo group. In clinical trials, the incidence of malignancies other than lymphoma was not increased with exposure to SIMPONI^® and was similar to what would be expected in the general population. Cases of acute and chronic leukemia have been reported with postmarketing TNF‑blocker use. The risks and benefits of TNF‑blocker therapy should be considered prior to initiating therapy in patients with a known malignancy or who develop a malignancy.

HEPATITIS B REACTIVATION

The use of TNF‑blocking agents including SIMPONI^® has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers. In some instances, HBV reactivation occurring in conjunction with TNF‑blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants.

All patients should be tested for HBV infection before initiating TNF‑blocker therapy. For patients who test positive for hepatitis B surface antigen, consult a physician with expertise in the treatment of hepatitis B before initiating TNF‑blocker therapy. Exercise caution when prescribing SIMPONI^® for patients identified as carriers of HBV and closely monitor for active HBV infection during and following termination of therapy with SIMPONI^®. Discontinue SIMPONI^® in patients who develop HBV reactivation, and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of SIMPONI^®, and monitor patients closely.

HEART FAILURE

Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported. Exercise caution and monitor patients with heart failure. Discontinue SIMPONI^® if new or worsening symptoms of heart failure appear.

DEMYELINATING DISORDERS

TNF‑blocking agents, of which SIMPONI^® is a member, have been associated with rare cases of new-onset or exacerbation of demyelinating disorders, including multiple sclerosis (MS) and Guillain-Barré syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported with SIMPONI^®. Exercise caution in considering the use of SIMPONI^® in patients with these disorders. Consider discontinuation if these disorders develop.

HEMATOLOGIC CYTOPENIAS

There have been reports of pancytopenia, leukopenia, neutropenia, and thrombocytopenia in patients receiving SIMPONI^® in clinical trials. Additionally, aplastic anemia has been reported in patients receiving TNF‑blocking agents, of which SIMPONI^® is a member. Exercise caution when using SIMPONI^® in patients who have or had significant cytopenias.

USE WITH OTHER DRUGS

The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections, therefore the use of SIMPONI^® in combination with these products is not recommended. Care should be taken when switching from one biologic to another since overlapping biological activity may further increase the risk of infection. A higher rate of serious infections has also been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker.

VACCINATIONS

People receiving SIMPONI^® can receive vaccinations, except for live vaccines. Administration of live vaccines to infants exposed to SIMPONI^® in utero is not recommended for 6 months following the mother's last SIMPONI^® injection during pregnancy due to an increased risk of infection.

HYPERSENSITIVITY REACTIONS

Serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported with SIMPONI^®, some occurring after the first dose. If an anaphylactic or other serious allergic reaction occurs, discontinue SIMPONI^® immediately and institute appropriate therapy.

ADVERSE REACTIONS

The most serious adverse reactions were serious infections and malignancies.

Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 trials through Week 16, occurring in 7% and 6% of patients treated with SIMPONI^® as compared with 6% and 5% of patients in the control group, respectively. The rate of injection-site reactions was 6% with patients treated with SIMPONI^® compared with 2% of patients in the control group.

Please see accompanying full Prescribing Information and Medication Guide for SIMPONI^®. Provide the Medication Guide to your patients and encourage discussion.