Data from FDA - Curated by EPG Health - Last updated 04 March 2018

Indication(s)

1 INDICATIONS AND USAGE SIMPONI ARIA is a tumor necrosis factor (TNF) blocker indicated for the treatment of adult patients with: Moderately to severely active Rheumatoid Arthritis (RA) in combination with methotrexate (1.1) Active Psoriatic Arthritis (PsA) (1.2) Active Ankylosing Spondylitis (AS) (1.3) 1.1 Rheumatoid Arthritis (RA) SIMPONI ARIA, in combination with methotrexate (MTX), is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis. 1.2 Psoriatic Arthritis (PsA) SIMPONI ARIA is indicated for the treatment of adult patients with active psoriatic arthritis. 1.3 Ankylosing Spondylitis (AS) SIMPONI ARIA is indicated for the treatment of adult patients with active ankylosing spondylitis.

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Advisory information

contraindications
4 CONTRAINDICATIONS None. None (4)
Adverse reactions
6 ADVERSE REACTIONS The most serious adverse reactions were: Serious Infections [see Warnings and Precautions (5.1)] Malignancies [see Warnings and Precautions (5.2)] Most common adverse reactions (incidence ≥ 3%) are: upper respiratory tract infection, alanine aminotransferase increased, viral infection, aspartate aminotransferase increased, neutrophil count decreased, bronchitis, hypertension, and rash (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 one, randomized, double-blind, controlled Phase 3 trial in patients with RA receiving SIMPONI ARIA by intravenous infusion (Trial RA). The protocol included provisions for patients taking placebo to receive treatment with SIMPONI ARIA at Week 16 or Week 24 either by patient response (based on uncontrolled disease activity) or by design, so that adverse events cannot always be unambiguously attributed to a given treatment. Comparisons between placebo and SIMPONI ARIA were based on the first 24 weeks of exposure. Trial RA included 197 control-treated patients and 463 SIMPONI ARIA-treated patients (which includes control-treated patients who switched to SIMPONI ARIA at Week 16). The proportion of patients who discontinued treatment due to adverse reactions in the controlled phase of Trial RA through Week 24 was 3.5% for SIMPONI ARIA-treated patients and 0.5% for placebo-treated patients. Upper respiratory tract infection was the most common adverse reaction reported in the trial through Week 24 occurring in 6.5% of SIMPONI ARIA-treated patients as compared with 7.6% of control-treated patients, respectively. Infections Serious infections observed in SIMPONI ARIA-treated patients included sepsis, pneumonia, cellulitis, abscess, opportunistic infections, tuberculosis (TB), and invasive fungal infections. Cases of TB included pulmonary and extrapulmonary TB. The majority of the TB cases occurred in countries with a high incidence rate of TB [see Warnings and Precautions (5.1)]. In the controlled phase of Trial RA through Week 24, infections were observed in 27% of SIMPONI ARIA-treated patients compared with 24% of control-treated patients, and serious infections were observed in 0.9% of SIMPONI ARIA-treated patients and 0.0% of control-treated patients. Through Week 24, the incidence of serious infections per 100 patient-years of follow-up was 2.2 (95% CI 0.61, 5.71) for the SIMPONI ARIA group, and 0 (0.00, 3.79) for the placebo group. In the controlled and uncontrolled portions of Trial RA, 958 total patient-years of follow-up with a median follow-up of approximately 92 weeks, the incidence per 100 patient-years of all serious infections was 4.07 (95% CI: 2.90, 5.57) in patients receiving SIMPONI ARIA [see Warnings and Precautions (5.1)]. In the controlled and uncontrolled portions of Trial RA, in SIMPONI ARIA-treated patients, the incidence of active TB per 100 patient-years was 0.31 (95% CI: 0.06; 0.92) and the incidence of other opportunistic infections per 100 patient-years was 0.42 (95% CI: 0.11, 1.07). Malignancies One case of malignancy other than lymphoma and NMSC with SIMPONI ARIA was reported through Week 24 during the controlled phase of Trial RA. In the controlled and uncontrolled portions through approximately 92 weeks, the incidence of malignancies per 100 patient-years, other than lymphoma and NMSC, in SIMPONI ARIA-treated patients was 0.31 (95% CI: 0.06, 0.92) and the incidence of NMSC was 0.1 (95% CI: 0.00, 0.58). Liver Enzyme Elevations There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In the controlled phase of Trial RA, through Week 24, ALT elevations ≥ 5 × ULN occurred in 0.8% of SIMPONI ARIA-treated patients and 0% of control-treated patients and ALT elevations ≥ 3 × ULN occurred in 2.3% of SIMPONI ARIA-treated patients and 2.5% of control-treated patients. In the controlled phase of Trial PsA, through Week 24, ALT elevations ≥ 5 × ULN occurred in 1.7% of SIMPONI ARIA-treated patients and <1% of placebo-treated patients, and ALT elevations ≥ 3 × ULN to < 5 × ULN occurred in 2.9% of SIMPONI ARIA-treated patients and <1% of placebo-treated patients. Since many of the patients in the Phase 3 trials were also taking medications that cause liver enzyme elevations (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], MTX, or isoniazid prophylaxis), the relationship between SIMPONI ARIA and liver enzyme elevation is not clear. Autoimmune Disorders and Autoantibodies At Week 20 in Trial RA, 17% of SIMPONI ARIA-treated patients and 13% of control patients were newly antinuclear antibody (ANA)-positive. Of these patients, one SIMPONI ARIA-treated patient and no control-treated patients had newly positive anti-dsDNA antibodies [see Warnings and Precautions (5.5)]. Administration Reactions In the controlled phase of Trial RA through Week 24, 1.1% of SIMPONI ARIA infusions were associated with an infusion reaction compared with 0.2% of infusions in the control group. The most common infusion reaction in SIMPONI ARIA-treated patients was rash. No serious infusion reactions were reported. Other Adverse Reactions Table 1 summarizes the adverse drug reactions that occurred at a rate of at least 1% in the SIMPONI ARIA + MTX group with a higher incidence than in the placebo + MTX group during the controlled period of Trial RA through Week 24. Table 1: Adverse Drug Reactions Reported by ≥ 1% of SIMPONI ARIA-Treated Patients and with a Higher Incidence than Placebo-Treated Patients in Trial RA through Week 24 Placebo + MTX SIMPONI ARIA + MTX Patients treated 197 463 Adverse Reaction Infections and infestations Upper respiratory tract infection (such as upper respiratory tract infection, nasopharyngitis, pharyngitis, laryngitis, and rhinitis) 12% 13% Viral infections (such as influenza and herpes) 3% 4% Bacterial infections 0% 1% Bronchitis 1% 3% Vascular disorders Hypertension 2% 3% Skin and subcutaneous disorders Rash 1% 3% General disorders and administration site conditions Pyrexia 1% 2% Blood and lymphatic disorders Leukopenia 0% 1% Other and Less Common Clinical Trial Adverse Drug Reactions Adverse drug reactions that do not appear in Table 1 or that occurred < 1% in SIMPONI ARIA-treated patients during Trial RA through Week 24 that do not appear in the Warnings and Precautions section included the following events listed by system organ class: Infections and infestations: Superficial fungal infection, sinusitis, abscess, lower respiratory tract infection (pneumonia), pyelonephritis Investigations: Alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, neutrophil count decreased Nervous system disorders: Dizziness, paresthesia Gastrointestinal disorders: Constipation Psoriatic Arthritis Trial PsA evaluated 480 patients [see Clinical Studies (14.2)]. The adverse reactions were similar to those observed in patients with RA, with the exception of psoriasis (new onset or worsening, palmar/plantar and pustular), which occurred in <1% of SIMPONI ARIA-treated patients. The incidence of the adverse reactions reported in Trial PsA were similar to Trial RA with the exceptions of higher incidence in SIMPONI ARIA for ALT increased (7.9% vs. 2.1% in placebo), AST increased (5.4% vs. 2.1% in placebo), and neutrophil count decreased (4.6% vs. 2.1% in placebo). Ankylosing Spondylitis Trial AS evaluated 208 patients [see Clinical Studies (14.3)]. The adverse reactions were similar to those reported in patients with RA, with the exception of the higher incidence of ALT increased, which occurred in 2.9% of SIMPONI ARIA-treated patients compared with none of the placebo-treated patients. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to golimumab in the trials described below with the incidence of antibodies in other trials or to other products may be misleading. Using an enzyme immunoassay (EIA) method, antibodies to golimumab were detected in 13 (3%) golimumab-treated patients following IV administration of SIMPONI ARIA in combination with MTX through Week 24 of Trial RA, of which all were neutralizing antibodies. A drug-tolerant enzyme immunoassay (drug-tolerant EIA) method for detecting antibodies to golimumab was developed and validated. This method is approximately 16-fold more sensitive than the original EIA method with less interference from golimumab in serum. The incidence of antibodies to golimumab with the drug-tolerant EIA method for Trials RA, PsA and AS was 21%, 19% and 19%, respectively. Where tested, approximately one-third were neutralizing. Patients with RA, PsA and AS who developed anti-golimumab antibodies generally had lower trough steady-state serum concentrations of golimumab [see Pharmacokinetics (12.3)]. 6.3 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 golimumab exposure. General Disorders and Administration Site Conditions: Infusion-related reactions [see Warnings and Precautions (5.11)] Neoplasm benign and malignant: Melanoma, Merkel cell carcinoma [see Warnings and Precautions (5.2)] Immune system disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction) [see Warnings and Precautions (5.11)], sarcoidosis Respiratory, thoracic and mediastinal disorders: Interstitial lung disease Skin and subcutaneous tissue disorders: Skin exfoliation, bullous skin reactions

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION 2 mg/kg intravenous infusion over 30 minutes at weeks 0 and 4, then every 8 weeks (2.1) Dilution of supplied SIMPONI ARIA solution with 0.9% Sodium Chloride Injection, USP is required prior to administration. Alternatively, 0.45% Sodium Chloride Injection, USP can also be used (2.3) 2.1 Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis The SIMPONI ARIA dosage regimen is 2 mg per kg given as an intravenous infusion over 30 minutes at weeks 0 and 4, then every 8 weeks thereafter. For patients with rheumatoid arthritis (RA), SIMPONI ARIA should be given in combination with methotrexate. For patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS), SIMPONI ARIA may be given with or without methotrexate or other non-biologic Disease-modifying Antirheumatic Drugs (DMARDs). Corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with SIMPONI ARIA. The efficacy and safety of switching between intravenous and subcutaneous formulations and routes of administration have not been established. 2.2 Evaluation for Tuberculosis and Hepatitis B Prior to Dosage Prior to initiating SIMPONI ARIA and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection [see Warnings and Precautions (5.1)]. Prior to initiating SIMPONI ARIA, test patients for hepatitis B viral infection [see Warnings and Precautions (5.1)]. 2.3 Important Administration Instructions SIMPONI ARIA solution for intravenous infusion should be diluted by a healthcare professional using aseptic technique as follows: Calculate the dosage and the number of SIMPONI ARIA vials needed based on the recommended dosage of 2 mg/kg and the patient's weight. Each 4 mL vial of SIMPONI ARIA contains 50 mg of golimumab. Check that the solution in each vial is colorless to light yellow. The solution may develop a few fine translucent particles, as golimumab is a protein. Do not use if opaque particles, discoloration, or other foreign particles are present. Dilute the total volume of the SIMPONI ARIA solution with 0.9% Sodium Chloride Injection, USP to a final volume of 100 mL. For example, this can be accomplished by withdrawing a volume of the 0.9% Sodium Chloride Injection, USP from the 100-mL infusion bag or bottle equal to the total volume of SIMPONI ARIA. Slowly add the total volume of SIMPONI ARIA solution to the 100-mL infusion bag or bottle. Gently mix. Discard any unused solution remaining in the vials. Alternatively, SIMPONI ARIA can be diluted using the same method described above with 0.45% Sodium Chloride Injection, USP. Prior to infusion, visually inspect the diluted SIMPONI ARIA solution for particulate matter or discoloration. Do not use if these exist. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.22 micrometer or less). Do not infuse SIMPONI ARIA concomitantly in the same intravenous line with other agents. No physical biochemical compatibility studies have been conducted to evaluate the use of SIMPONI ARIA with other intravenous agents in the same intravenous line. Infuse the diluted solution over 30 minutes. Once diluted, the infusion solution can be stored for 4 hours at room temperature.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled trials of SIMPONI ARIA in pregnant women. Monoclonal antibodies, such as golimumab, are transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. There are clinical considerations for the use of SIMPONI ARIA in pregnant women [see Clinical Considerations]. In an animal reproductive study, golimumab administered by the subcutaneous route to pregnant monkeys, during the period of organogenesis, at doses that produced exposures approximately 200 times the maximum recommended human dose (MRHD) had no adverse fetal effects. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and of miscarriage is 15–20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Golimumab crosses the placenta during pregnancy. Another TNF-blocking monoclonal antibody administered during pregnancy was detected for up to 6 months in the serum of infants. Consequently, these infants may be at increased risk of infection. 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 [see Warnings and Precautions (5.10) and Drug Interactions (7.3)]. Data Human Data Limited data on use of SIMPONI ARIA in pregnant women from observational studies, published case reports, and postmarketing surveillance are insufficient to inform a drug associated risk. Animal Data In an embryofetal developmental toxicology study in which pregnant cynomolgus monkeys were treated with golimumab during the period of organogenesis from gestation days (GD) 20 to 51, exposures up to 200 times greater than the exposure at the MRHD (on an area under the curve (AUC) basis with maternal subcutaneous doses up to 50 mg/kg twice weekly) produced no evidence of fetal malformations or embryotoxicity. There was no evidence of maternal toxicity. Umbilical cord blood samples collected at the end of the second trimester showed that fetuses were exposed to golimumab during gestation. In a pre- and postnatal developmental study in which pregnant cynomolgus monkeys were treated with golimumab from gestation day 50 to postpartum day 33, maximal drug concentrations up to 33 times greater than that found with the MRHD (on a maximum blood concentration (Cmax) basis at steady-state with maternal subcutaneous doses up to 50 mg/kg twice weekly) were not associated with any evidence of developmental defects in infants. There was no evidence of maternal toxicity. Golimumab was present in fetal serum at the end of the second trimester and in neonatal serum from the time of birth and for up to 6 months postpartum. 8.2 Lactation Risk Summary There is no information regarding the presence of SIMPONI ARIA in human milk, the effects on breastfed infants, or the effects on milk production. Maternal IgG is known to be present in human milk. If golimumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to golimumab are unknown. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for SIMPONI ARIA and any potential adverse effects on the breast-fed infants from SIMPONI ARIA, or from the underlying maternal condition. Data Animal Data In the pre- and postnatal development study in cynomolgus monkeys in which golimumab was administered subcutaneously during pregnancy and lactation, golimumab was detected in the breast milk at concentrations that were approximately 400-fold lower than the maternal serum concentrations. 8.4 Pediatric Use Safety and effectiveness of SIMPONI ARIA in pediatric patients less than 18 years of age have not been established. Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with other TNF-blocking agents [see Warnings and Precautions (5.2)]. 8.5 Geriatric Use In Trial RA, the number of patients ages 65 or older was too small to make comparisons with younger SIMPONI ARIA-treated patients. Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with SIMPONI ARIA.

Interactions

7 DRUG INTERACTIONS Biologics, including abatacept and anakinra: Increased risk of serious infection (5.1, 5.6, 5.7, 5.8, 7.2) Live vaccines should not be given with SIMPONI ARIA (5.10, 7.3). 7.1 Methotrexate SIMPONI ARIA should be used with MTX for the treatment of RA [see Clinical Studies (14.1)]. Following IV administration, concomitant administration of methotrexate decreases the clearance of SIMPONI ARIA by approximately 9% based on population pharmacokinetics (PK) analysis. In addition, concomitant administration of methotrexate decreases the SIMPONI ARIA clearance by reducing the development of antibodies to golimumab. SIMPONI ARIA may be used with or without MTX for the treatment of PsA or AS [see Clinical Studies (14.2 and 14.3) and Clinical Pharmacology (12.3)]. 7.2 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 ARIA with other biologic products, including abatacept or anakinra, is not recommended [see Warnings and Precautions (5.6 and 5.7)]. 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, PsA or AS is not recommended because of the possibility of an increased risk of infection. 7.3 Live Vaccines/Therapeutic Infectious Agents Live vaccines should not be given concurrently with SIMPONI ARIA [see Warnings and Precautions (5.10)]. Therapeutic infectious agents should not be given concurrently with SIMPONI ARIA [see Warnings and Precautions (5.10)]. Infants born to women treated with SIMPONI ARIA during their pregnancy may be at increased risk of infection for up to 6 months. 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 [see Use in Specific Populations (8.1)]. 7.4 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 ARIA 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.

More information

Category Value
Authorisation number BLA125433
Agency product number 91X1KLU43E
Orphan designation No
Product NDC 57894-350
Date Last Revised 15-02-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 1431647
Storage and handling Storage and Stability SIMPONI ARIA must be refrigerated at 2º C to 8º C (36º F to 46º F) and protected from light. Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake.
Marketing authorisation holder Janssen Biotech, Inc.
Warnings 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 ARIA (5.1). Discontinue SIMPONI ARIA 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 ARIA (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 ARIA is a member (5.2). SERIOUS INFECTIONS Patients treated with SIMPONI ARIA 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 ARIA if a patient develops a serious infection. Reported infections with TNF blockers, of which SIMPONI ARIA 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 ARIA use and during therapy. Initiate treatment for latent tuberculosis 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. 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 ARIA 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 ARIA, 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 ARIA is a member [see Warnings and Precautions (5.2)].