FDA label 02ee9cf4-c6d6-4239-854e-7c5976977456

WARNING: SERIOUS INFECTIONS AND MALIGNANCY WARNING: SERIOUS INFECTIONS AND MALIGNANCY See full prescribing information for complete boxed warning. Serious infections leading to hospitalization or death including tuberculosis (TB), bacterial sepsis, invasive fungal (such as histoplasmosis), and other opportunistic infections have occurred in patients receiving SIMPONI ( 5.1 ) Discontinue SIMPONI if a patient develops a serious infection or sepsis ( 5.1 ) Perform test for latent TB; if positive, start treatment for TB prior to starting SIMPONI ( 5.1 ) Monitor all patients for active TB during treatment, even if initial latent TB test is negative ( 5.1 ) Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which SIMPONI is a member ( 5.2 ) SERIOUS INFECTIONS Patients treated with SIMPONI are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1) ] . 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, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Test patients for latent tuberculosis before SIMPONI use and during therapy. Initiate treatment for latent TB 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. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal 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 prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with SIMPONI, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions (5.1) ] . MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which SIMPONI is a member [see Warnings and Precautions (5.2) ] .

5 WARNINGS AND PRECAUTIONS Serious Infections: Do not start SIMPONI during an active infection. If an infection develops, monitor carefully, and stop SIMPONI if infection becomes serious ( 5.1 ) Invasive Fungal Infections: For patients who develop a systemic illness on SIMPONI, consider empiric antifungal therapy for those who reside in or travel to regions where mycoses are endemic ( 5.1 ) Malignancies: Incidence of lymphoma was greater than in the general U.S. population. Cases of other malignancies have been observed among patients receiving TNF blockers ( 5.2 ) Congestive Heart Failure: Worsening, or new onset, may occur. Stop SIMPONI if new or worsening symptoms occur ( 5.3 ) Demyelinating Disorders: Exacerbation or new onset may occur ( 5.4 ) Hepatitis B Reactivation: Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop SIMPONI and begin antiviral therapy ( 5.5 ) Lupus-like Syndrome: Discontinue SIMPONI if symptoms develop ( 5.6 ) Hypersensitivity Reactions: Serious systemic hypersensitivity reactions including anaphylaxis may occur ( 5.12 ) 5.1 Serious Infections Patients treated with SIMPONI 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 have been 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 was associated with a higher risk of serious infections; therefore, the concomitant use of SIMPONI and these biologic products is not recommended [see Warnings and Precautions (5.6 , 5.7) and Drug Interactions (7.2) ] . Treatment with SIMPONI 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 the risks and benefits of treatment prior to initiating SIMPONI in patients: with chronic or recurrent infection; who have been exposed to tuberculosis; with a history of an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or with underlying conditions that may predispose them to infection. Monitoring Closely monitor patients for the development of signs and symptoms of infection during and after treatment with SIMPONI. Discontinue SIMPONI if a patient develops a serious infection, an opportunistic infection, or sepsis. For a patient who develops a new infection during treatment with SIMPONI, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor them. Serious Infection in Clinical Trials In controlled Phase 3 trials through Week 16 in patients with RA, PsA, and AS, serious infections were observed in 1.4% of SIMPONI-treated patients and 1.3% of control-treated patients. In the controlled Phase 3 trials through Week 16 in patients with RA, PsA, and AS, the incidence of serious infections per 100 patient-years of follow-up was 5.7 (95% CI: 3.8, 8.2) for the SIMPONI group and 4.2 (95% CI: 1.8, 8.2) for the placebo group. In the controlled Phase 2/3 trial through Week 6 of SIMPONI induction in UC, the incidence of serious infections in SIMPONI 200/100 mg-treated patients was similar to the incidence of serious infections in placebo-treated patients. Through Week 60, the incidence of serious infections was similar in patients who received SIMPONI induction and 100 mg during maintenance compared with patients who received SIMPONI induction and placebo during the maintenance portion of the UC trial. Serious infections observed in SIMPONI-treated patients included sepsis, pneumonia, cellulitis, abscess, tuberculosis, invasive fungal infections, and hepatitis B infection. 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 SIMPONI 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 SIMPONI, 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 SIMPONI 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 the 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 SIMPONI during and after treatment for latent tuberculosis. Monitor patients for the 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 SIMPONI treatment, 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. In the controlled and uncontrolled portions of the Phase 2 RA and Phase 3 RA, PsA, and AS trials, the incidence of active TB was 0.23 and 0 per 100 patient-years in 2347 SIMPONI-treated patients and 674 placebo-treated patients, respectively. Cases of TB included pulmonary and extrapulmonary TB. The overwhelming majority of the TB cases occurred in countries with a high incidence rate of TB. In the controlled Phase 2/3 trial of SIMPONI induction through Week 6 in UC, no cases of TB were observed in SIMPONI 200/100 mg-treated patients or in placebo-treated patients. Through Week 60, the incidence per 100 patient-years of TB in patients who received SIMPONI induction and 100 mg during the maintenance portion of the UC trial was 0.52 (95% CI: 0.11, 1.53). One case of TB was observed in the placebo maintenance group in a patient who received SIMPONI intravenous (IV) induction. Invasive 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 the 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. 5.2 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), 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 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 the 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, including SIMPONI, 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. In the controlled portions of clinical trials of TNF blockers, including SIMPONI, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with patients in the control groups. During the controlled portions of the Phase 2 trials in RA, and the Phase 3 trials in RA, PsA and AS, 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 the controlled and uncontrolled portions of these clinical trials in 2347 SIMPONI-treated patients with a median follow-up of 1.4 years, the incidence of lymphoma was 3.8-fold higher than expected in the general U.S. population according to the 1964–2004 data from SEER database (adjusted for age, gender, and race). Through Week 60 of the UC trials, there were no cases of lymphoma with SIMPONI. Patients with RA and other chronic inflammatory diseases, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy. Cases of acute and chronic leukemia have been reported with TNF-blocker use, including SIMPONI, in rheumatoid arthritis and other indications. Even in the absence of TNF-blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia. Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been 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 patients treated with TNF blockers cannot be excluded. During the controlled portions of the Phase 2 trial in RA, and the Phase 3 trials in RA, PsA and AS, the incidence of malignancies other than lymphoma per 100 patient-years of follow-up was not elevated in the combined SIMPONI group compared with the placebo group. In the controlled and uncontrolled portions of these trials, the incidence of malignancies, other than lymphoma, in SIMPONI-treated patients was similar to that expected in the general U.S. population according to the 1969–2004 SEER database (adjusted for age, gender, and race). In the 6-week placebo-controlled portions of the SIMPONI Phase 2/3 clinical trials in UC, the incidence of non-lymphoma malignancies (excluding nonmelanoma skin cancer) was similar between the SIMPONI and the placebo group. Through Week 60, the incidence of non-lymphoma malignancies (excluding nonmelanoma skin cancer) was similar to the general U.S. population according to the 1969–2004 SEER database (adjusted for age, gender, and race). Short follow-up periods, such as those of one year or less in the studies above, may not adequately reflect the true incidence of malignancies . It is not known if SIMPONI treatment influences the 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 treated with SIMPONI, 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 have been reported in patients treated with TNF-blocking agents, including SIMPONI. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. In controlled trials of other TNF blockers in patients at higher risk for malignancies (e.g., patients with chronic obstructive pulmonary disease [COPD], patients with Wegener's granulomatosis treated with concomitant cyclophosphamide) a greater portion of malignancies occurred in the TNF-blocker group compared to the controlled group. In an exploratory 1-year clinical trial evaluating the use of 50 mg, 100 mg, and 200 mg of SIMPONI in 309 patients with severe persistent asthma, 6 patients developed malignancies other than NMSC in the SIMPONI groups compared to none in the control group. Three of the 6 patients were in the 200 mg SIMPONI group. 5.3 Congestive Heart Failure Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers, including SIMPONI. 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. SIMPONI has not been studied in patients with a history of CHF and SIMPONI should be used with caution in patients with CHF. If a decision is made to administer SIMPONI to patients with CHF, these patients should be closely monitored during therapy, and SIMPONI should be discontinued if new or worsening symptoms of CHF appear. 5.4 Demyelinating Disorders Use of TNF blockers, of which SIMPONI is a member, 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. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported in patients treated with SIMPONI [see Adverse Reactions (6.1) ] . Prescribers should exercise caution in considering the use of TNF blockers, including SIMPONI, in patients with central or peripheral nervous system demyelinating disorders. Discontinuation of SIMPONI should be considered if these disorders develop. 5.5 Hepatitis B Virus Reactivation The use of TNF blockers including SIMPONI has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers (i.e., 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 the 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, including SIMPONI, to patients who are carriers of HBV. Adequate data are not available on whether antiviral therapy can reduce the 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 should be initiated. The safety of resuming TNF blockers after HBV reactivation has been controlled is not known. Therefore, prescribers should exercise caution when considering resumption of TNF blockers in this situation and monitor patients closely. 5.6 Autoimmunity Treatment with TNF blockers, including SIMPONI, may result in the formation of antinuclear antibodies (ANA) and, rarely, in the development of a lupus-like syndrome [see Adverse Reactions (6.1) ] . If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with SIMPONI, treatment should be discontinued. 5.7 Use with Abatacept In controlled trials, the concurrent administration of another TNF blocker and abatacept was associated with a greater proportion of serious infections than the use of a TNF blocker alone; and the combination therapy, compared to the use of a TNF blocker alone, has not demonstrated improved clinical benefit in the treatment of RA. Therefore, the combination of TNF blockers, including SIMPONI, and abatacept is not recommended [see Drug Interactions (7.2) ] . 5.8 Use with Anakinra Concurrent administration of anakinra (an interleukin-1 antagonist) and another TNF blocker was associated with a greater portion of serious infections and neutropenia and no additional benefits compared with the TNF-blocker alone. Therefore, the combination of anakinra with TNF blockers, including SIMPONI, is not recommended [see Drug Interactions (7.2) ] . 5.9 Switching Between Biological Disease-Modifying Antirheumatic Drugs Care should be taken when switching from one biological product to another biological product since overlapping biological activity may further increase the risk of infection. 5.10 Hematologic Cytopenias There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia in patients receiving golimumab. Caution should be exercised when using TNF blockers, including SIMPONI, in patients who have or have had significant cytopenias. 5.11 Vaccinations/Therapeutic Infectious Agents Live Vaccines Patients treated with SIMPONI may receive vaccinations, except for live vaccines. In patients receiving anti-TNF therapy, limited data are available on the response to live vaccination, or on the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections. If possible, it is recommended that prior to initiating therapy with SIMPONI, pediatric patients be brought up to date with all immunizations in agreement with current immunization guidelines. Therapeutic Infectious Agents Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with SIMPONI. Non-live Vaccines In the Phase 3 PsA trial, after pneumococcal vaccination, a similar proportion of SIMPONI-treated and placebo-treated patients were able to mount an adequate immune response of at least a 2-fold increase in antibody titers to pneumococcal polysaccharide vaccine. In both SIMPONI-treated and placebo-treated patients, the proportions of patients with response to pneumococcal vaccine were lower among patients receiving MTX compared with patients not receiving MTX. The data suggest that SIMPONI does not suppress the humoral immune response to the pneumococcal vaccine. 5.12 Hypersensitivity Reactions In postmarketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following SIMPONI administration. Some of these reactions occurred after the first administration of SIMPONI. If an anaphylactic or other serious allergic reaction occurs, administration of SIMPONI should be discontinued immediately and appropriate therapy instituted.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions (5.1) ] Malignancies [see Warnings and Precautions (5.2) ] Congestive Heart Failure [see Warnings and Precautions (5.3) ] Demyelinating Disorders [see Warnings and Precautions (5.4) ] Hepatitis B Reactivation [see Warnings and Precautions (5.5) ] Autoimmunity [see Warnings and Precautions (5.6) ] Hematologic Cytopenias [see Warnings and Precautions (5.10) ] Hypersensitivity Reactions [see Warnings and Precautions (5.12) ] Most common adverse reactions in adults (incidence > 5%) are upper respiratory tract infection, nasopharyngitis, injection site reactions ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. The safety data described below are based on: Five pooled, randomized, double-blind, controlled Phase 3 trials in patients with RA, PsA, and AS (Trials RA-1, RA-2, RA-3, PsA, and AS) [see Clinical Studies (14.1 , 14.2 , and 14.3) ] . These 5 trials included 639 control-treated patients and 1659 SIMPONI-treated patients including 1089 with RA, 292 with PsA, and 278 with AS. Three pooled, randomized, double-blind, controlled Phase 2/3 in 1233 SIMPONI-treated adult patients with UC (Trials UC-1, UC-2, and UC-3 (NCT03596645)) [see Clinical Studies (14.4) ] . An open-label trial in 69 SIMPONI-treated pediatric patients weighing at least 15 kg with UC (Trial UC-3) (NCT03596645) [see Clinical Studies (14.5) ] . The proportion of adult 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-treated patients and 3% for placebo-treated patients. The most common adverse reactions leading to discontinuation of SIMPONI in the controlled Phase 3 trials in RA, PsA and AS through Week 16 were sepsis (0.2%), alanine aminotransferase increased (0.2%), and aspartate aminotransferase increased (0.2%). The most common adverse drug reactions leading to discontinuation through Week 60 of the UC trials in adult patients who received SIMPONI induction and 100 mg during maintenance compared with patients who received SIMPONI induction and placebo during maintenance were tuberculosis (0.3% vs. 0.6%) and anemia (0.3% vs. 0%), respectively. Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 RA, PsA and AS trials in adults through Week 16, occurring in 7% and 6% of SIMPONI-treated patients as compared with 6% and 5% of control-treated patients, respectively. Infections In adult controlled Phase 3 trials through Week 16 in RA, PsA, and AS, infections were observed in 28% of SIMPONI-treated patients compared to 25% of control-treated patients. For serious infections, see the Warnings and Precautions section [see Warnings and Precautions (5.1) ] . In Trial UC-1, the rates of infections were similar in SIMPONI 200/100 mg-treated patients and placebo-treated patients, or approximately 12%. Through Week 60, the incidence per patient year of infections was similar in patients who received SIMPONI induction and 100 mg during maintenance compared with patients who received SIMPONI induction and placebo during the maintenance period Trial UC-2. Demyelinating Disorders In Trial UC-1 of SIMPONI induction through Week 6, no cases of demyelination were observed in SIMPONI 200/100 mg-treated patients or placebo-treated patients. Through Week 60 in Trial UC-2, there were no cases of demyelination in the SIMPONI 100 mg group during maintenance. One case of CNS demyelination was observed in the placebo maintenance group in a patient who received SIMPONI 400/200 mg during induction. Liver Enzyme Elevations There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF blockers. In adult controlled Phase 3 trials of SIMPONI in patients with RA, PsA, and AS through Week 16, ALT elevations ≥ 5 × ULN occurred in 0.2% of control-treated patients and 0.7% of SIMPONI-treated patients and ALT elevations ≥ 3 × ULN occurred in 2% of control-treated patients and 2% of SIMPONI-treated patients. Since many of the patients in the Phase 3 trials for RA, PsA, and AS were also taking medications that cause liver enzyme elevations (e.g., NSAIDs, MTX), the relationship between SIMPONI and liver enzyme elevation is not clear. In Trials UC-1, UC-2, and UC-3, the incidence of ALT elevations ≥ 5 × ULN was similar in SIMPONI-treated patients and placebo-treated patients, or approximately 1%, with an average duration of follow-up of 46 weeks and 18 weeks, respectively. ALT elevations ≥ 3 × ULN occurred in 2.0% of SIMPONI-treated patients compared with 1.5% of placebo-treated patients with an average duration of follow-up of 46 weeks and 18 weeks, respectively. Autoimmune Disorders and Autoantibodies In the adult controlled Phase 3 trials in patients with RA, PsA, and AS through Week 14, there was no association of SIMPONI treatment and the development of newly positive anti-dsDNA antibodies. In Phase 3 trials in RA, PsA, and AS through 1 year of follow-up, 4.0% of SIMPONI-treated patients and 2.6% of control patients were newly antinuclear antibody (ANA)-positive (at titers of 1:160 or greater). The frequency of anti-dsDNA antibodies at 1 year of follow-up was uncommon in patients who were anti-dsDNA negative at baseline. Through Week 60 of the UC trials (Trials UC-1, UC-2, and UC-3), 3.5% of patients who received SIMPONI induction and 100 mg during maintenance were newly ANA-positive (at titers of 1:160 or greater) compared with 3.5% of patients who received SIMPONI induction and placebo during the maintenance period in Trial UC-2. The frequency of anti-dsDNA antibodies at 1 year of follow-up in patients who were anti-dsDNA negative at baseline was 0.5% in patients receiving SIMPONI induction and 100 mg during maintenance compared with 0% in patients who received SIMPONI induction and placebo during maintenance [see Warnings and Precautions (5.6) ] . Injection Site Reactions In adult controlled Phase 3 trials through Week 16 in RA, PsA and AS, 6% of SIMPONI-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 Trial UC-1, 3.4% of SIMPONI-treated patients had injection site reactions compared with 1.5% in control-treated patients. The majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site erythema. In adult controlled Phase 2 and 3 trials in RA, PsA, AS, no patients treated with SIMPONI developed anaphylactic reactions. Other Adverse Reactions Table 2 summarizes the adverse drug reactions that occurred at a rate of at least 1% in the SIMPONI ± DMARD group and with a higher incidence than in the placebo ± DMARD group during the controlled period of the 5 pooled Phase 3 trials through Week 16 in adult patients with RA, PsA, and AS. Table 2: Adverse Drug Reactions Reported by ≥ 1% of SIMPONI-Treated Patients and with a Higher Incidence Than Placebo-Treated Patients in the Adult Phase 3 Trials of RA, PsA, and AS through Week 16 Patients may have taken concomitant MTX, sulfasalazine, hydroxychloroquine, low dose corticosteroids (≤ 10 mg of prednisone/day or equivalent), and/or NSAIDs during the trials). SIMPONI ± DMARDs Placebo ± DMARDs Patients treated 1659 639 Adverse Reaction Infections and infestations Upper respiratory tract infection (nasopharyngitis, pharyngitis, laryngitis, and rhinitis) 16% 13% Viral infections (such as influenza and herpes) 5% 3% Bronchitis 2% 1% Superficial fungal infections 2% 1% Sinusitis 2% 1% General disorders and administration site conditions Injection site reaction (injection site erythema, urticaria, induration, pain, bruising, pruritus, irritation, paresthesia) 6% 2% Investigations Alanine aminotransferase increased 4% 3% Aspartate aminotransferase increased 3% 2% Vascular disorders Hypertension 3% 2% Nervous system disorders Dizziness 2% 1% Paresthesia 2% 1% Gastrointestinal disorders Constipation 1% <1% Less Common Clinical Trial Adverse Drug Reactions Adverse drug reactions that occurred <1% in adult SIMPONI-treated patients in the RA, PsA and AS clinical trials that do not appear in the Warnings and Precautions section included the following events listed by system organ class: Infections and infestations: Septic shock, atypical mycobacterial infection, pyelonephritis, arthritis bacterial, bursitis infective Neoplasms benign, malignant and unspecified: Leukemia Skin and subcutaneous tissue disorders: Psoriasis (new onset or worsening, palmar/plantar and pustular), vasculitis (cutaneous) Vascular disorders: Vasculitis (systemic) Adults and Pediatric Patients Weighing at least 15 kg with Ulcerative Colitis In general, adverse reactions reported in adult patients with UC in Trials UC-1, UC-2, and UC-3 were similar to those reported in clinical trials of patients with RA, PsA, and AS. Adverse reactions reported in the clinical trial of pediatric patients weighing at least 15 kg with UC were also similar to those reported in clinical trials of adults with UC and the other indicated populations. Additional adverse reactions reported in at least 10% of pediatric patients in the trial were headache (17%) and pyrexia (10%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of golimumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to SIMPONI exposure. Immune system disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction) [see Warnings and Precautions (5.12) ] , sarcoidosis Neoplasms benign, malignant and unspecified: Melanoma, Merkel cell carcinoma [see Warnings and Precautions (5.2) ] Respiratory, thoracic and mediastinal disorders: Interstitial lung disease Skin and subcutaneous tissue disorders : Skin exfoliation, lichenoid reactions, rash, bullous skin reactions

<table width="75%"><caption>Table 2: Adverse Drug Reactions Reported by &#x2265; 1% of SIMPONI-Treated Patients and with a Higher Incidence Than Placebo-Treated Patients in the Adult Phase 3 Trials of RA, PsA, and AS through Week 16 <footnote ID="K2224">Patients may have taken concomitant MTX, sulfasalazine, hydroxychloroquine, low dose corticosteroids (&#x2264; 10 mg of prednisone/day or equivalent), and/or NSAIDs during the trials).</footnote></caption><col width="40%" align="left" valign="top"/><col width="30%" align="center" valign="top"/><col width="30%" align="center" valign="top"/><thead><tr><th/><th align="left">SIMPONI &#xB1; DMARDs</th><th align="left">Placebo &#xB1; DMARDs</th></tr></thead><tbody><tr><td>Patients treated</td><td>1659</td><td>639</td></tr><tr><td>Adverse Reaction</td><td/><td/></tr><tr><td><content styleCode="bold">Infections and infestations</content></td><td/><td/></tr><tr><td> Upper respiratory tract infection (nasopharyngitis, pharyngitis, laryngitis, and rhinitis)</td><td>16%</td><td>13%</td></tr><tr><td> Viral infections (such as influenza and herpes)</td><td>5%</td><td>3%</td></tr><tr><td> Bronchitis</td><td>2%</td><td>1%</td></tr><tr><td> Superficial fungal infections</td><td>2%</td><td>1%</td></tr><tr><td> Sinusitis</td><td>2%</td><td>1%</td></tr><tr><td><content styleCode="bold">General disorders and administration site conditions</content></td><td/><td/></tr><tr><td> Injection site reaction (injection site erythema, urticaria, induration, pain, bruising, pruritus, irritation, paresthesia)</td><td>6%</td><td>2%</td></tr><tr><td><content styleCode="bold">Investigations</content></td><td/><td/></tr><tr><td> Alanine aminotransferase increased</td><td>4%</td><td>3%</td></tr><tr><td> Aspartate aminotransferase increased</td><td>3%</td><td>2%</td></tr><tr><td><content styleCode="bold">Vascular disorders</content></td><td/><td/></tr><tr><td> Hypertension</td><td>3%</td><td>2%</td></tr><tr><td><content styleCode="bold">Nervous system disorders</content></td><td/><td/></tr><tr><td> Dizziness</td><td>2%</td><td>1%</td></tr><tr><td> Paresthesia</td><td>2%</td><td>1%</td></tr><tr><td><content styleCode="bold">Gastrointestinal disorders</content></td><td/><td/></tr><tr><td> Constipation</td><td>1%</td><td>&lt;1%</td></tr></tbody></table>