IMPORTANT SAFETY INFORMATION
Patients treated with SIMPONI® ARIA™ (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® ARIA™ if a patient develops a serious infection.
Reported infections with TNF blockers, of which SIMPONI® ARIA™ is a member, include:
- Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before SIMPONI® ARIA™ use and during therapy. Initiate treatment for latent infection prior to SIMPONI® ARIA™ 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.
Consider the risks and benefits of treatment with SIMPONI® ARIA™ prior to initiating therapy in patients with chronic or recurrent infection. Do not start SIMPONI® ARIA™ 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® ARIA™, 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® ARIA™ included sepsis, pneumonia, cellulitis, and abscess.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which SIMPONI® ARIA™ 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 TNF blockers including the subcutaneous formulation of golimumab, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with patients in the control groups. In clinical trials, the incidence of malignancies other than lymphoma and non-melanoma skin cancer per 100 patient-years of follow-up was 0.56 (95% CI: 0.01, 3.11) in the SIMPONI® ARIA™ group compared with an incidence of 0 (95% CI: 0.00, 3.79) in the placebo group. 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.
Melanoma has been reported in patients treated with TNF-blocking agents, including the subcutaneous formulation of golimumab. Merkel cell carcinoma has been reported in patients treated with TNF-blocking agents. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
HEPATITIS B REACTIVATION
The use of TNF blockers, of which SIMPONI® ARIA™ is a member, 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® ARIA™ for patients identified as carriers of HBV and closely monitor for active HBV infection during and following termination of therapy with SIMPONI® ARIA™. Discontinue SIMPONI® ARIA™ in patients who develop HBV reactivation, and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of SIMPONI® ARIA™, and monitor patients closely.
Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported. Exercise caution in CHF patients receiving SIMPONI® ARIA™ and monitor them closely during therapy. Discontinue SIMPONI® ARIA™ if new or worsening symptoms of heart failure appear.
Use of TNF blockers, of which SIMPONI® ARIA™ is a member, has 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 in patients treated with the subcutaneous formulation of golimumab. Exercise caution in considering the use of SIMPONI® ARIA™ in patients with these disorders. Consider discontinuation if these disorders develop.
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® ARIA™ 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. The concomitant use of SIMPONI® ARIA™ with biologics approved to treat RA is not recommended because of the possibility of an increased risk of infection.
There have been reports of pancytopenia, leukopenia, neutropenia, and thrombocytopenia in patients receiving SIMPONI® ARIA™ in clinical trials. Additionally, aplastic anemia has been reported in patients receiving TNF blockers. Exercise caution when using SIMPONI® ARIA™ in patients who have or had significant cytopenias.
People receiving SIMPONI® ARIA™ can receive vaccinations, except for live vaccines. Administration of live vaccines to infants exposed to SIMPONI® ARIA™ in utero is not recommended for 6 months following the mother´s last SIMPONI® ARIA™ infusion during pregnancy due to an increased risk of infection.
Serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following administration of the subcutaneous formulation of golimumab, some occurring after the first dose. If an anaphylactic or other serious allergic reaction occurs, discontinue SIMPONI® ARIA™ immediately and institute appropriate therapy.
The most serious adverse reactions were serious infections and malignancies.
Upper respiratory tract infection was the most common adverse reaction reported in the Phase 3 trial through Week 24, occurring in 6.5% of patients treated with SIMPONI® ARIA™ as compared with 7.6% of patients in the control group. The rate of infusions associated with an infusion reaction was reported in 1.1% of SIMPONI® ARIA™ infusions compared with 0.2% of infusions in the control group.