Golimumab

Q: What should I know before taking Golimumab?

5 WARNINGS AND PRECAUTIONS Serious Infections: Do not start SIMPONI ARIA during an active infection. If an infection develops, monitor carefully, and stop SIMPONI ARIA if infection becomes serious ( 5.1 ). Invasive Fungal Infections: For patients who develop a systemic illness on SIMPONI ARIA, consider empiric antifungal therapy for those who reside in or travel to regions where mycoses are endemic ( 5.1 ). Hepatitis B Reactivation: Monitor HBV carriers during and several months after therapy. I

Q: Is Golimumab available over the counter?

Golimumab is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Prescription

Nama merek: SIMPONI ARIA

Bentuk Sediaan

Injection

Rute Pemberian

INTRAVENOUS

Produsen

Janssen Biotech, Inc.

About This Medication

11 DESCRIPTION Golimumab is a human IgG1қ monoclonal antibody specific for human tumor necrosis factor alpha (TNFα) that exhibits multiple glycoforms with molecular masses of approximately 150 to 151 kilodaltons. Golimumab was created using genetically engineered mice immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions. Golimumab is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses. The SIMPONI ARIA ® (golimumab) Injection is a sterile solution of the golimumab antibody supplied in a 4-mL glass vial for intravenous infusion. SIMPONI ARIA is a preservative-free, colorless to light yellow solution with a pH of approximately 5.5. SIMPONI ARIA is not made with natural rubber latex. Each 4-mL vial of SIMPONI ARIA contains 50 mg golimumab, L-histidine (1.14 mg), L-histidine monohydrochloride monohydrate (6.42 mg), polysorbate 80 (0.6 mg), sorbitol (180 mg), and water for injection.

Bahan Aktif

Bahan	Kekuatan
Golimumab	-

Indikasi & Penggunaan

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) in patients 2 years of age and older ( 1.2 ) Adult patients with active Ankylosing Spondylitis (AS) ( 1.3 ) Active polyarticular Juvenile Idiopathic Arthritis (pJIA) in patients 2 years of age and older ( 1.4 ) 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 active psoriatic arthritis in patients 2 years of age and older. 1.3 Ankylosing Spondylitis (AS) SIMPONI ARIA is indicated for the treatment of adult patients with active ankylosing spondylitis. 1.4 Polyarticular Juvenile Idiopathic Arthritis (pJIA) SIMPONI ARIA is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older.

Cara kerja

12.1 Mechanism of Action Golimumab is a human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNFα. This interaction prevents the binding of TNFα to its receptors, thereby inhibiting the biological activity of TNFα (a cytokine protein). There was no evidence of the golimumab antibody binding to other TNF superfamily ligands; in particular, the golimumab antibody did not bind or neutralize human lymphotoxin. Golimumab did not lyse human monocytes expressing transmembrane TNF in the presence of complement or effector cells. Elevated TNFα levels in the blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. TNFα is an important mediator of the articular inflammation that is characteristic of these diseases. Golimumab modulated the in vitro biological effects mediated by TNF in several bioassays, including the expression of adhesion proteins responsible for leukocyte infiltration (E-selectin, ICAM-1 and VCAM-1) and the secretion of proinflammatory cytokines (IL-6, IL-8, G-CSF and GM-CSF). The clinical relevance of these findings is unknown.

Dosis & Cara Pemberian

2 DOSAGE AND ADMINISTRATION Adult patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: 2 mg/kg intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter ( 2.1 ) Pediatric patients with polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis: 80 mg/m 2 intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter ( 2.2 ) 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 ( 2.4 ) 2.1 Dosage in Adults with 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, and every 8 weeks thereafter. Follow the dilution and administration instructions for SIMPONI ARIA [see Dosage and Administration (2.4) ] . For patients with rheumatoid arthritis (RA), SIMPONI ARIA should be given in combination with methotrexate. The efficacy and safety of switching between intravenous and subcutaneous formulations and routes of administration have not been established. 2.2 Dosage in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis The SIMPONI ARIA dosage regimen, based on body surface area (BSA), is 80 mg/m 2 given as an intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter. Follow the dilution and administration instructions for SIMPONI ARIA [see Dosage and Administration (2.4) ] . 2.3 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) ] . 2.4 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 adult dosage of 2 mg/kg and the patient's weight for RA, PsA and AS. Calculate the dosage and number of SIMPONI ARIA vials needed based on the recommended pediatric dosage of 80 mg/m 2 and the patient's body surface area (BSA), for pJIA and pediatric patients with PsA. 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 are present. 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 up to 4 hours at room temperature.

Side Effects Overview

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. Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis Trial pJIA evaluated 127 patients with JIA with active polyarthritis [see Use in Specific Populations (8.4) and Clinical Studies (14.4) ]. The adverse reactions observed were consistent with the established safety profile of SIMPONI ARIA in adult patients with RA and PsA. 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. Through approximately 6 months, the incidence of antibodies to golimumab with the drug-tolerant EIA method for Trials RA, PsA, AS, and pJIA was 21%, 19%, 19% and 31%, respectively. Where tested, approximately one-third to one-half were neutralizing. Patients with RA, PsA, AS and pJIA who developed antibodies to golimumab generally had lower trough steady-state serum concentrations of golimumab [see Clinical Pharmacology (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, lichenoid reactions, bullous skin reactions

Peringatan & Tindakan Pencegahan

5 WARNINGS AND PRECAUTIONS Serious Infections: Do not start SIMPONI ARIA during an active infection. If an infection develops, monitor carefully, and stop SIMPONI ARIA if infection becomes serious ( 5.1 ). Invasive Fungal Infections: For patients who develop a systemic illness on SIMPONI ARIA, consider empiric antifungal therapy for those who reside in or travel to regions where mycoses are endemic ( 5.1 ). Hepatitis B Reactivation: Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop SIMPONI ARIA and begin anti-viral therapy ( 5.1 ). Malignancies: More cases of lymphoma have been observed among patients receiving TNF blockers compared with patients in the control groups. 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 ARIA if new or worsening symptoms occur ( 5.3 ). Demyelinating Disorders: Exacerbation or new onset may occur ( 5.4 ). Lupus-like Syndrome: Discontinue SIMPONI ARIA if symptoms develop ( 5.5 ). Hypersensitivity Reactions: Serious systemic hypersensitivity reactions including anaphylaxis may occur ( 5.11 ). 5.1 Serious Infections Patients treated with SIMPONI ARIA 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 ARIA and these biologic products is not recommended [see Warnings and Precautions (5.6 , 5.7) and Drug Interactions (7.2) ] . Treatment with SIMPONI ARIA 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 ARIA 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 ARIA. Discontinue SIMPONI ARIA if a patient develops a serious infection, an opportunistic infection, or sepsis. For patients who develop a new infection during treatment with SIMPONI ARIA, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient and 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 SIMPONI ARIA 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 ARIA, 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 ARIA 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 the subcutaneous formulation of golimumab 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 ARIA 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. 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. Hepatitis B Virus 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 (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 ARIA, 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. 5.2 Malignancies Malignancies in Pediatric Patients 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), including golimumab. 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. Most cases were reported postmarketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports. Malignancies in Adult Patients The risks and benefits of TNF-blocker treatment including SIMPONI ARIA should be considered prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma 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 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. 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 ARIA, 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. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with TNF-blockers cannot be excluded. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including SIMPONI ARIA. 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 clinical trial evaluating the use of the subcutaneous formulation of golimumab in patients with severe persistent asthma, more patients treated with golimumab reported malignancies compared with control patients. The significance of this finding is unknown. During the controlled portion of the Phase 3 trial in RA for SIMPONI ARIA, the incidence of malignancies other than lymphoma and NMSC 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. 5.3 Congestive Heart Failure Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF-blockers, including SIMPONI ARIA. 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 ARIA has not been studied in patients with a history of CHF and SIMPONI ARIA should be used with caution in patients with CHF. If a decision is made to administer SIMPONI ARIA to patients with CHF, these patients should be closely monitored during therapy, and SIMPONI ARIA should be discontinued if new or worsening symptoms of CHF appear. 5.4 Demyelinating Disorders Use of TNF-blockers, including SIMPONI ARIA, 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 golimumab. Prescribers should exercise caution in considering the use of TNF-blockers, including SIMPONI ARIA, in patients with central or peripheral nervous system demyelinating disorders. Discontinuation of SIMPONI ARIA should be considered if these disorders develop. 5.5 Autoimmunity Treatment with TNF blockers, including SIMPONI ARIA, may result in the formation of antinuclear antibodies (ANA). Rarely, treatment with TNF blockers, may result 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 ARIA, treatment should be discontinued. 5.6 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 ARIA, and abatacept is not recommended [see Drug Interactions (7.2) ] . 5.7 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 ARIA, is not recommended [see Drug Interactions (7.2) ] . 5.8 Switching Between Biological Disease Modifying Antirheumatic Drugs (DMARDs) 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. 5.9 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 ARIA, in patients who have or have had significant cytopenias. 5.10 Vaccinations/Therapeutic Infectious Agents Live Vaccines Avoid live vaccines in patients treated with SIMPONI ARIA. 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. 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 Drug Interactions (7.3) and Use in Specific Populations (8.1) ] . Whenever possible update immunizations prior to initiation of treatment with SIMPONI ARIA following current immunization guidelines for patients receiving immunosuppressive agents. Advise patients to discuss with the physician before seeking any immunizations. 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 ARIA. 5.11 Hypersensitivity Reactions In postmarketing experience, serious systemic hypersensitivity reactions (including anaphylaxis) have been reported following administration of the subcutaneous and intravenous formulations of golimumab including SIMPONI ARIA. Hypersensitivity reactions including hives, pruritus, dyspnea, and nausea, were reported during infusion and generally within an hour after infusion. Some of these reactions occurred after the first administration of golimumab. If an anaphylactic or other serious allergic reaction occurs, administration of SIMPONI ARIA should be discontinued immediately and appropriate therapy instituted.

Kontraindikasi

4 CONTRAINDICATIONS None. None ( 4 )

Farmakokinetik

12.3 Pharmacokinetics Golimumab exhibited approximately dose-proportional pharmacokinetics in patients with RA over the dose range of 0.1 to 10.0 mg/kg following a single intravenous dose. Absorption Following a single intravenous administration of 2 mg/kg SIMPONI ARIA, a mean C max of 44.4 ± 11.3 mcg/mL was observed in patients with RA. Data directly comparing 2 mg/kg intravenous administration and 50 mg subcutaneous administration are not available. Distribution Following a single intravenous administration of 2 mg/kg SIMPONI ARIA, the mean volume of distribution was estimated to be 115 ± 19 mL/kg in healthy subjects, and 151 ± 61 mL/kg in patients with RA. The volume of distribution of golimumab may indicate that golimumab is distributed primarily in the circulatory system with limited extravascular distribution. Elimination Following a single intravenous administration of 2 mg/kg SIMPONI ARIA, the systemic clearance of golimumab was estimated to be 6.9 ± 2.0 mL/day/kg in healthy subjects and 7.6 ± 2.0 mL/day/kg in patients with RA. The mean terminal half-life was estimated to be 12 ± 3 days in healthy subjects and the mean terminal half-life in RA patients was 14 ± 4 days. Multiple Doses When 2 mg/kg SIMPONI ARIA was administered intravenously to patients with RA at weeks 0, 4 and every 8 weeks thereafter, serum concentrations reached steady-state by Week 12. With concomitant use of MTX, treatment with 2 mg/kg SIMPONI ARIA every 8 weeks resulted in a mean steady-state trough serum concentration of approximately 0.4 ± 0.4 mcg/mL in patients with active RA. The mean steady-state trough serum concentration in patients with PsA was 0.7 ± 0.6 mcg/mL. The mean steady-state trough serum concentration in patients with AS was 0.8 ± 0.6 mcg/mL. Patients with RA, PsA and AS who developed antibodies to golimumab generally had lower trough steady-state serum concentrations of golimumab [see Adverse Reactions (6.2) ]. Specific Populations No formal study of the effect of renal or hepatic impairment on the PK of golimumab was conducted. Body Weight Following intravenous administration, patients with higher body weight tended to have slightly higher serum golimumab concentrations than patients with lower body weights when golimumab was administered on a mg/kg (body weight) basis. However, based on population PK analysis, there were no clinically relevant differences in golimumab exposure following intravenous administration of 2 mg/kg SIMPONI ARIA in adult patients across a range of different body weights. Pediatrics When 80 mg/m 2 SIMPONI ARIA was administered intravenously to patients with JIA with active polyarthritis at weeks 0, 4 and every 8 weeks thereafter, serum concentrations reached steady-state by Week 12. With concomitant use of MTX, treatment with 80 mg/m 2 SIMPONI ARIA resulted in a mean steady-state trough serum golimumab concentration of approximately 0.5 ± 0.4 mcg/mL and a mean steady-state AUC of 425 ± 125 mcg∙day/mL in patients with JIA with active polyarthritis. Overall, the observed steady-state golimumab trough concentrations in patients with JIA with active polyarthritis were within the range of those observed for adult RA and PsA after administration of SIMPONI ARIA. Consistent with the intravenous data in adult patients with RA, population pharmacokinetic analyses for intravenous SIMPONI ARIA in pJIA revealed that there were no clinically relevant differences in golimumab exposure following intravenous administration of 80 mg/m 2 SIMPONI ARIA in pediatric patients across a range of age and different body weights. The immune response effect on golimumab clearance in patients with JIA with active polyarthritis was comparable to adults with RA. Drug Interaction Studies Specific drug interaction studies have not been conducted with SIMPONI ARIA. Population PK analysis indicated that concomitant use of MTX, NSAIDs, oral corticosteroids, or sulfasalazine (SSZ) did not significantly influence the clearance of golimumab following IV administration.

Frequently Asked Questions

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) in patients 2 years of age and older ( 1.2 ) Adult patients with active Ankylosing Spondylitis (AS) ( 1.3 ) Active polyarticular Juvenile Idiopathic Arthritis (pJIA) in patients 2 years of age and older ( 1.4 ) 1.1 Rheumatoid Arthritis …

2 DOSAGE AND ADMINISTRATION Adult patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis: 2 mg/kg intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter ( 2.1 ) Pediatric patients with polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis: 80 mg/m 2 intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter ( 2.2 ) Dilution of supplied SIMPONI ARIA solution with 0.9% Sodium Chloride Injection, USP is required prior …

5 WARNINGS AND PRECAUTIONS Serious Infections: Do not start SIMPONI ARIA during an active infection. If an infection develops, monitor carefully, and stop SIMPONI ARIA if infection becomes serious ( 5.1 ). Invasive Fungal Infections: For patients who develop a systemic illness on SIMPONI ARIA, consider empiric antifungal therapy for those who reside in or travel to regions where mycoses are endemic ( 5.1 ). Hepatitis B Reactivation: Monitor HBV carriers during and several months after therapy. If reactivation occurs, …

4 CONTRAINDICATIONS None. None ( 4 )

Golimumab is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

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References & Data Sources

• DailyMed — Golimumab drug label (National Library of Medicine)
• openFDA — Golimumab label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 1431642 (NLM Normalized Drug Names)
• NDC Directory — Golimumab (FDA National Drug Code)

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Sumber data: DailyMed (NLM), openFDA, MFDS