administration of therapy; if an anaphylactic or other serious allergic reaction occurs, therapy should be discontinued immediately and appropriate therapy instituted Infections Treated patients are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis reported with TNF blockers Patients have frequently presented with disseminated rather than localized disease; the concomitant use of a TNF blocker and abatacept or anakinra has been associated with a higher risk of serious infections; the concomitant use with these biologic products not recommended Treatment should not be initiated in patients with an active infection, including clinically important localized infections; patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection; consider risks and benefits of treatment prior to initiating in following patients with chronic or recurrent infection, who have been exposed to tuberculosis, have a history of an opportunistic infection, have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis, or have underlying conditions that may predispose them to infection Closely monitor patients for the development of signs and symptoms of infection during and after treatment; discontinue treatment if a patient develops a serious infection, an opportunistic infection, or sepsis; for a patient who develops a new infection during treatment, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor them Tuberculosis Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF blockers, including patients who have previously received treatment for latent or active tuberculosis; evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating treatment and periodically during therapy Treatment of latent tuberculosis infection prior to therapy with TNF blockers has been shown to reduce the risk of tuberculosis reactivation during therapy; prior to initiating treatment, assess if treatment for latent tuberculosis is needed; an induration of 5 mm or greater is a positive tuberculin skin test, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG) Consider anti-tuberculosis therapy prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection Consultation with a physician with expertise in treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient Cases of active tuberculosis have occurred in patients treated with golimumab during and after treatment for latent tuberculosis; monitor patients for development of signs and symptoms of tuberculosis including patients who tested negative for latent tuberculosis infection prior to initiating therapy, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection Consider tuberculosis in the differential diagnosis in patients who develop a new infection during therapy, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis Fungal infections If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis; consider appropriate empiric antifungal therapy, and take into account both the risk for severe fungal infection and risks of antifungal therapy while a diagnostic workup is being performed; antigen and antibody testing for histoplasmosis may be negative in some patients with active infection; to aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections Hepatitis B virus reactivation The use of TNF blockers has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers (eg, surface antigen positive); 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, consultation with a physician with expertise in treatment of hepatitis B is recommended before initiating TNF-blocker therapy The risks and benefits of treatment should be considered prior to prescribing TNF blockers to patients who are carriers of HBV; adequate data are not available on whether antiviral therapy can reduce risk of HBV reactivation in HBV carriers who are treated with TNF blockers Patients who are carriers of HBV and require treatment with TNF blockers should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy In patients who develop HBV reactivation, TNF blockers should be stopped and antiviral therapy with appropriate supportive treatment initiated; the safety of resuming TNF blockers after HBV reactivation has been controlled is not known; prescribers should exercise caution when considering resumption of TNF blockers in this situation and monitor patients closely Malignancies Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age) 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 that are usually associated with immunosuppression, and malignancies that are not usually observed in children and adolescents The malignancies occurred after a median of 30 months (range 1 to 84 months) after first dose of TNF-blocker therapy; most of the patients were receiving concomitant immunosuppressants; these cases were reported postmarketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports The risks and benefits of TNF-blocker treatment should be considered prior to initiating therapy in patients with a known malignancy other than a successfully treated nonmelanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) reported in patients treated with TNF-blocking agents; this rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal; nearly all of the reported TNF blocker associated cases have occurred in patients with Crohn's disease or ulcerative colitis The majority were in adolescent and young adult males; almost all these patients had received treatment with azathioprine (AZA) or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis; the potential risk with the combination of AZA or 6-MP and SIMPONI should be carefully considered; a risk for the development for hepatosplenic T-cell lymphoma in patientstreated with TNF blockers cannot be excluded It is not known if the treatment influences risk for developing dysplasia or colon cancer; all patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course This evaluation should include colonoscopy and biopsies per local recommendations; in patients with newly diagnosed dysplasia receiving therapy, the risks and benefits to the individual patient must be carefully reviewed and consideration should be given to whether therapy should be continued Melanoma and Merkel cell carcinoma reported in patients treated with TNF-blocking agents; periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer Congestive heart failure Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers; some cases had a fatal outcome; in several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality Golimumab has not been studied in patients with a history of CHF and should be used with caution in patients with CHF; if a decision is made to administer therapy to patients with CHF, these patients should be closely monitored during therapy, and the drug should be discontinued if new or worsening symptoms of CHF appear Demyelinating disorders Use of TNF blockers has been associated with rare cases of new onset or exacerbation of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS) and peripheral demyelinating disorders, including Guillain-Barré syndrome; casesof central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy reported in patients receiving therapy Prescribers should exercise caution in considering the use of TNF blockers in patients with central or peripheral nervous system demyelinating disorders; discontinuation of therapy should be considered if these disorders develop Drug interactions overview Infection risk increases when coadministered with abatacept, anakinra, abatacept, or rituximab; combination is not recommended Care should be taken when switching from one biologic product to another biologic product since overlapping biological activity may further increase the risk of infection Increased risk of serious infections seen in clinical RA studies of other TNF-blockers used in combination with no added benefit May decrease humoral response to live-virus vaccines (eg, MMR) Whenever possible update immunizations prior to initiation of treatment, following current immunization guidelines for patients receiving immunosuppressive agents; advise patients to discuss with physician before seeking any immunizations Limited data are available on response to live vaccination, or on secondary transmission of infection by live vaccines for patients receiving anti-TNF therapy Administration of live virus vaccines and therapeutic agents (eg, BCG bladder instillation) may result in disseminated infections; avoid live vaccines Formation of CYP450 enzymes may be suppressed by increased levels of cytokines (eg, TNF-alpha) during chronic inflammation; molecules (eg, golimumab) that antagonizes cytokine activity may normalize the formation of CYP450 enzymes; upon initiation or discontinuation of treatment in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effects (eg, warfarin) or drug concentrations (eg, cyclosporine or theophylline) is recommended and adjusting individual doses of the drug products as needed Pregnancy There are no adequate and well-controlled trials in pregnant women; monoclonal antibodies are transported across the placenta during the third trimester and may affect immune response in the in utero exposed infant Use during pregnancy only if clearly needed Clinical considerations Golimumab crosses the placenta during pregnancy; another TNF-blocking monoclonal antibody administered during pregnancy detected for up to 6 months in serum of infants; consequently, infants may be at increased risk of infection Live vaccines administration to infants exposed to golimumab in utero is not recommended for 6 months following the mother’s last dose during pregnancy Lactation There is no information regarding the presence in human milk, the effects on breastfed infants, or the effects on milk production Maternal IgG is known to be present in human milk; the effects of local exposure in gastrointestinal tract and potential limited systemic exposure in the infant to golimumab are unknown; developmental and health benefits of breast-feeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breast-fed infants or from the underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Human anti-TNF-alpha monoclonal antibody, binds to both soluble and transmembrane bioactive forms of human TNFα; prevents binding of TNF-alpha to its receptors, thereby inhibiting biological activity of TNFα (a cytokine protein) Absorption Bioavailability: ~53% Peak plasma concentration Simponi Aria: 44.4 mcg/mL Simponi: 3.2 mcg/mL. Peak plasma time Simponi: 2-6 days (RA) Distribution Vd Simponi Aria: 115 mL/kg (healthy patients); 151 mL/kg (RA) Simponi: 58-126 mL/kg Metabolism Exact metabolic pathway unknown Elimination