Simponi

— THERAPEUTIC CATEGORIES —
  • Arthritis/rheumatic disorders
  • Colorectal disorders
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Simponi Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Golimumab 50mg/0.5mL, 100mg/mL; soln for SC inj; preservative-free.

    Pharmacological Class

    TNF-alpha blocker.

    How Supplied

    Single-dose prefilled syringe—1; Single-dose SmartJect autoinjector—1

    How Supplied

    Simponi (golimumab) Injection is a preservative-free, sterile, clear to slightly opalescent, colorless to light yellow solution for subcutaneous use in a single-dose prefilled autoinjector (contains a prefilled glass syringe) or single-dose prefilled glass syringe. The Type 1 glass syringe has a coated stopper. The fixed stainless steel needle (5 bevel, 27G, ½ inch) is covered with a needle shield to prevent leakage of the solution through the needle and to protect the needle during handling prior to subcutaneous administration. The needle shield is made of a dry natural rubber containing latex. Simponi is supplied as follows:

    • 50 mg/0.5 mL single-dose prefilled syringe: 1 pack

    • 100 mg/mL single-dose prefilled syringe: 1 pack 

    • 50 mg/0.5 mL single-dose prefilled SmartJect® autoinjector: 1 pack 

    • 100 mg/mL single-dose prefilled SmartJect® autoinjector: 1 pack

     

    Storage

    Refrigerate Simponi at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light until the time of use. Do not freeze. Do not shake. Do not use Simponi beyond the expiration date (EXP) on the carton or the expiration date on the prefilled syringe (observed through the viewing window) or the prefilled SmartJect autoinjector.

    If needed, Simponi may be stored at room temperature up to 77°F (25°C) for a maximum single period of 30 days in the original carton to protect from light. Once a syringe or autoinjector has been stored at room temperature, do not return the product to the refrigerator. If not used within 30 days at room temperature, discard Simponi.

    Manufacturer

    Janssen Biotech, Inc.

    Generic Availability

    NO

    Simponi Indications

    Indications

    Moderately-to-severely active rheumatoid arthritis (RA), in combination with methotrexate (MTX). Active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS), with or without MTX or other nonbiologic DMARDs.

    Simponi Dosage and Administration

    Adult

    50mg SC once monthly. Rotate inj sites. Corticosteroids, non-biologic DMARDs, and/or NSAIDs may be continued during treatment.

    Children

    <18yrs: not established.

    Simponi Contraindications

    Not Applicable

    Simponi Boxed Warnings

    Boxed Warning

    Serious infections. Malignancy.

    Boxed Warning

    Serious Infections

    • Increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

    • Discontinue Simponi 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. 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. 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 prior to initiating therapy in patients with chronic or recurrent infection. 

    • Monitor closely for signs and symptoms of infection during and after treatment, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

    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.

    Simponi Warnings/Precautions

    Warnings/Precautions

    Increased risk of serious or fatal infections (eg, TB, bacterial sepsis, viral, invasive fungal [treat empirically if develops], or other pathogens). Active infections: do not initiate therapy. Chronic or history of recurring or opportunistic infections. Conditions that predispose to infection. Travel to, or residence in, areas with endemic TB or mycoses. Test/treat latent TB and HBV infection prior to initiating therapy. Monitor closely if new infection, active TB (even if initial latent test is negative), reactivation of HBV, or blood dyscrasias occurs; discontinue if serious or opportunistic infection, sepsis, HBV reactivation, new or worsening CHF, hematological abnormality (eg, cytopenias), lupus-like syndrome, or serious hypersensitivity reaction develops. Malignancies. Perform periodic skin exams (esp. those with skin cancer risk factors). Prior history of dysplasia or colon carcinoma; monitor. CHF (monitor). Immunosuppression. CNS demyelinating disorders. Latex allergy. Elderly. Infants (see Interactions). Pregnancy. Nursing mothers.

    Warnings/Precautions

    Serious Infections

    • Increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. 

    • The concomitant use of a TNF blocker and abatacept or anakinra is not recommended due to a higher risk of serious infections.

    • Do not initiate 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. 

    • Prior to initiating Simponi, consider the risks and benefits of treatment:

      • 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: 

      • Monitor closely for signs and symptoms of infection during and after treatment with Simponi. 

      • Discontinue if a patient develops a serious infection, an opportunistic infection, or sepsis. 

      • If a new infection develops during treatment with Simponi: perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor them. 

    • Tuberculosis: 

      • Prior to initiating Simponi and periodically during therapy, evaluate for tuberculosis risk factors and test for latent infection.

      • Assess if treatment for latent tuberculosis is needed prior to initiating therapy; 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.

      • Monitor for 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.

    • 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.

    • Hepatitis B Virus Reactivation: 

      • Test all patients for HBV infection before initiating. If positive for hepatitis B surface antigen, consultation with an expert physician in the treatment of hepatitis B is recommended before initiating.

      • Considered risks and benefits of treatment to patients who are carriers of HBV prior to prescribing TNF blockers. 

      • For patients who are carriers of HBV and require treatment with TNF blockers: monitor closely for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.

      • Discontinue and initiate antiviral therapy with appropriate supportive treatment if HBV reactivation occurs. The safety of resuming TNF blockers after HBV reactivation has been controlled is not known. Use caution when considering resumption of TNF blockers in this situation and monitor patients closely.

    Malignancies

    • Consider the risks and benefits of TNF-blocker treatment, including Simponi, prior to initiating therapy in patients with a known malignancy other than a successfully treated nonmelanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy.  

    • Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF-blocking agents. 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. Carefully consider the potential risk with the combination of AZA or 6-MP and Simponi. 

    • Screen for dysplasia at regular intervals before therapy and throughout their disease course in 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. 

    • Carefully review the risks and benefits in patients with newly diagnosed dysplasia treated with Simponi and consider whether therapy should be continued.

    • Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

    Congestive Heart Failure

    • Simponi has not been studied in patients with a history of CHF. Use caution in patients with CHF. 

    • If a decision is made to administer Simponi to patients with CHF, monitor closely during therapy, and discontinue if new or worsening symptoms of CHF appear. 

    Demyelinating Disorders 

    • Use caution in considering the use of TNF blockers, including Simponi, in patients with central (e.g., multiple sclerosis) or peripheral (e.g., Guillain-Barré syndrome) nervous system demyelinating disorders. 

    • Consider discontinuing if these disorders develop. 

    Autoimmunity

    • Discontinue If symptoms suggestive of a lupus-like syndrome develop following treatment with Simponi.

    Use with Abatacept

    • The concomitant 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.

    • The combination of TNF blockers, including Simponi, and abatacept is not recommended.

    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. 

    • The combination of anakinra with TNF blockers, including Simponi, is not recommended 

    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. 

    Hematologic Cytopenias 

    • Caution should be exercised when using TNF blockers, including Simponi, in patients who have or have had significant cytopenias. 

    Vaccinations/Therapeutic Infectious Agents 

    • Live Vaccines: May receive vaccinations, except for live vaccines, during therapy. 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. 

    • Therapeutic Infectious Agents: Recommended to not give therapeutic infectious agents concurrently with Simponi. 

    • Non-live Vaccines: The data suggest that Simponi does not suppress the humoral immune response to the pneumococcal vaccine.

    Hypersensitivity Reactions 

    • Discontinue immediately and institute appropriate therapy if an anaphylactic or other serious allergic reaction occurs. 

    Pregnancy Considerations

    Risk Summary

    • 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.

    • Only use during pregnancy if clearly needed.  

    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. 

    • Infants may be at increased risk of infection. Administration of live vaccines to infants exposed to Simponi in utero is not recommended for 6 months following the mother’s last Simponi injection during pregnancy.

    Nursing Mother Considerations

    Risk Summary

    • There is no information regarding the presence of Simponi in human milk, the effects on breastfed infants, or the effects on milk production.

    • The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for Simponi and any potential adverse effects on the breast-fed infants from Simponi, or from the underlying maternal condition. 

    Pediatric Considerations

    Effectiveness of Simponi in pediatric patients less than 18 years of age has not been established. 

    Geriatric Considerations

    Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with Simponi.

    Simponi Pharmacokinetics

    Absorption

    Following subcutaneous administration of Simponi to healthy subjects and patients with active RA, the median time to reach maximum serum concentrations (Tmax) ranged from 2 to 6 days. A subcutaneous injection of 50-mg Simponi to healthy subjects produced a mean ± standard deviation maximum serum concentration (Cmax) of 3.2 ± 1.4 mcg/mL. 

    By cross-trial comparisons of mean AUCinf values following an IV or subcutaneous administration of Simponi, the absolute bioavailability of subcutaneous Simponi was estimated to be approximately 53%. 

    Distribution

    Following a single IV administration over the dose range of 0.1 to 10.0 mg/kg in patients with active RA, mean volume of distribution ranged from 58 to 126 mL/kg. The volume of distribution for Simponi indicates that Simponi is distributed primarily in the circulatory system with limited extravascular distribution.  

    Metabolism

    The exact metabolic pathway of golimumab is unknown. 

    Elimination

    Following a single IV administration over the dose range of 0.1 to 10.0 mg/kg in patients with active RA, mean systemic clearance of Simponi was estimated to be 4.9 to 6.7 mL/day/kg.

    Median terminal half-life values were estimated to be approximately 2 weeks in healthy subjects and patients with active RA, PsA or AS.

    Simponi Interactions

    Interactions

    Concurrent abatacept, anakinra, live vaccines, therapeutic infectious agents, or other TNF blockers: not recommended. Infants exposed to golimumab in utero: do not give live vaccines for 6 months after mother’s last inj during pregnancy. Concomitant immunosuppressants (eg, corticosteroids, MTX) may increase risk of infection. Concomitant CYP450 substrates with narrow therapeutic index (eg, warfarin, cyclosporine, theophylline); monitor and may need dose adjustments of these drugs. Caution with switching between DMARDs; overlapping may further increase the risk of infection.

    Simponi Adverse Reactions

    Adverse Reactions

    Upper respiratory tract infection, nasopharyngitis, inj site reactions, viral infections; other serious infections, malignancies (eg, melanoma, lymphoma; monitor), blood dyscrasias, new or worsening CHF, elevated liver enzymes, antibody formation, exacerbation or new onset of psoriasis.

    Simponi Clinical Trials

    Clinical Trials

    Rheumatoid Arthritis

    The efficacy and safety of Simponi was evaluated in 3 multicenter, randomized, double-blind, controlled trials (Trials RA-1, RA-2, and RA-3), in a total of 1542 patients ≥18 years of age with moderately to severely active RA, diagnosed according to the American College of Rheumatology (ACR) criteria, for at least 3 months prior to administering Simponi. 

    Patients were required to have at least 4 swollen and 4 tender joints. Simponi was administered subcutaneously at doses of 50 mg or 100 mg every 4 weeks. Double-blinded controlled efficacy data were collected and analyzed through Week 24. Patients were allowed to continue stable doses of concomitant low dose corticosteroids (equivalent to ≤ 10 mg of prednisone a day) and/or NSAIDs and patients may have received oral MTX during the trials.  

    Trial RA-1 included 445 patients who were previously treated (at least 8 to 12 weeks prior to administration of trial agent) with one or more doses of a biologic TNF blocker without a serious adverse reaction. Patients were randomly assigned to receive placebo (N=150), Simponi 50 mg (N=147), or Simponi 100 mg (N=148). Patients were allowed to continue stable doses of concomitant MTX, sulfasalazine (SSZ), and/or hydroxychloroquine (HCQ) during the trial. The use of other DMARDs including cytotoxic agents or other biologics was prohibited.

    Trial RA-2 included 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who had not been previously treated with a biologic TNF blocker. Patients were randomly assigned to receive background MTX (N=133), Simponi 50 mg + background MTX (N=89), Simponi 100 mg + background MTX (N=89), or Simponi 100 mg monotherapy (N=133). The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited. 

    Trial RA-3 included 637 patients with active RA who were MTX naïve and had not previously been treated with a biologic TNF blocker. Patients were randomized to receive MTX (N=160), Simponi 50 mg + MTX (N=159), Simponi 100 mg + MTX (N=159), or Simponi 100 mg monotherapy (N=159). For patients receiving MTX, MTX was administered at a dose of 10 mg/week beginning at Week 0 and increased to 20 mg/week by Week 8. The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited. 

    The primary endpoint in Trial RA-1 and Trial RA-2 was the percentage of patients achieving an ACR 20 response at Week 14 and the primary endpoint in Trial RA-3 was the percentage of patients achieving an ACR 50 response at Week 24. 

    Results from all 3 RA trials showed that a greater proportion of patients treated with Symponi plus MTX achieved ACR responses compared with MTX alone. 

    In Trial RA-1, treatment with Symponi 50mg ± DMARDs achieved the following ACR responses vs placebo ± DMARDs, respectively:

    • ACR 20 

      • Week 14: 35% vs 18%

      • Week 24: 31% vs 16%

    • ACR 50 

      • Week 14: 15% vs 7%

      • Week 24: 16% vs 4%

    • ACR 70 

      • Week 14: 10% vs 2% 

      • Week 24: 9% vs 2%

    In Trial RA-2, treatment with Symponi 50mg plus background MTX achieved the following ACR responses vs background MTX alone, respectively:

    • ACR 20 

      • Week 14: 55% vs 33%

      • Week 24: 60% vs 28%

    • ACR 50 

      • Week 14: 35% vs 10%

      • Week 24: 37% vs 14%

    • ACR 70 

      • Week 14: 13% vs 4%

      • Week 24: 20% vs 5%

    In Trial RA-3, treatment with Symponi 50mg plus MTX achieved the following ACR responses vs MTX alone, respectively (data was not collected at week 14):

    • ACR 20 (week 24): 62% vs 49%

    • ACR 50 (week 24): 40% vs 29%

    • ACR 70 (week 24): 24% vs 16%

    For Trial RA-2, Symponi 50 mg plus background MTX achieved the following improvements in the individual ACR components at week 14 from baseline vs background MTX, respectively:

    • Number of swollen joints (0-66): 62% vs 38%

    • Number of tender joints (0-68): 60% vs 30%

    • Patient’s assessment of pain (0-10): 55% vs 18%

    • Patient’s global assessment of disease activity (0-10): 45% vs 15%

    • Physician’s global assessment of disease activity (0-10): 55% vs 35%

    • HAQ score (0-3): 29% vs 10%

    • CRP (mg/dL): 44% vs 2%

    In Trials RA-1 and RA-2, the Simponi 50-mg groups demonstrated a greater improvement compared to the control groups in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24: 0.23 vs. 0.03 in RA-1, 0.47 vs. 0.13 in RA-2, respectively. Also in Trials RA-1 and RA-2, the Simponi 50-mg groups compared to the control groups had a greater proportion of HAQ responders (change from baseline > 0.22) at Week 24: 43% vs. 27%, 65% vs. 35%, respectively.

     

    Psoriatic Arthritis

    The safety and efficacy of Simponi were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial in 405 adult patients with moderately to severely active PsA (≥ 3 swollen joints and ≥ 3 tender joints) despite NSAID or DMARD therapy (Trial PsA). Patients in this trial had a diagnosis of PsA for at least 6 months with a qualifying psoriatic skin lesion of at least 2 cm in diameter, and did not receive previous treatment with a biologic TNF blocker.

    Patients were randomly assigned to placebo (N=113), Simponi 50 mg (N=146), or Simponi 100 mg (N=146) given subcutaneously every 4 weeks. Patients were allowed to receive stable doses of concomitant MTX (≤ 25 mg/week), low dose oral corticosteroids (equivalent to ≤ 10 mg of prednisone a day), and/or NSAIDs during the trial. The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited. The primary endpoint was the percentage of patients achieving ACR 20 response at Week 14.

    Results showed that treatment with Symponi 50mg ± MTX achieved the following ACR responses vs placebo ± MTX, respectively:

    • ACR 20

      • Week 14: 51% vs 9%

      • Week 24: 52% vs 12%

    • ACR 50

      • Week 14: 30% vs 2%

      • Week 24: 32% vs 4%

    • ACR 70

      • Week 14: 12% vs 1%

      • Week 24: 19% vs 1%

    At week 14, treatment with Symponi 50mg ± MTX achieved the following percent improvements in ACR components vs placebo ± MTX, respectively:

    • Number of swollen joints (0-66): 60% vs 8%

    • Number of tender joints (0-68): 54% vs 0%

    • Patient’s assessment of pain (0-10): 48% vs -1%

    • Patient’s global assessment of disease activity (0-10): 49% vs 2%

    • Physician’s global assessment of disease activity (0-10): 59% vs 7%

    • HAQ score (0-3): 28% vs 0%

    • CRP (mg/dL): 40% vs 0%

    In Trial PsA, Simponi 50 mg demonstrated a greater improvement compared to placebo in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24 (0.33 and -0.01, respectively). In addition, the Simponi 50-mg group compared to the placebo group had a greater proportion of HAQ responders (≥ 0.3 change from baseline) at Week 24: 43% vs. 22%, respectively. 

     

    Ankylosing Spondylitis

    The safety and efficacy of Simponi were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial in 356 adult patients with active ankylosing spondylitis according to modified New York criteria for at least 3 months (Trial AS). Patients had symptoms of active disease [defined as a Bath AS Disease Activity Index (BASDAI) ≥ 4 and VAS for total back pain of ≥ 4, on scales of 0 to 10 cm] despite current or previous NSAID therapy.

    Patients were randomly assigned to placebo (N=78), Simponi 50 mg (N=138), or Simponi 100 mg (N=140) administered subcutaneously every 4 weeks. Patients were allowed to continue stable doses of concomitant MTX, sulfasalazine (SSZ), hydroxychloroquine (HCQ), low dose corticosteroids (equivalent to < 10 mg of prednisone a day), and/or NSAIDs during the trial. The use of other DMARDs including cytotoxic agents or other biologics was prohibited. The primary endpoint was the percentage of patients achieving an ASsessment in Ankylosing Spondylitis (ASAS) 20 response at Week 14.

    Results showed that treatment with Symponi 50mg ± DMARDs achieved the following ASAS responses vs placebo ± DMARDs, respectively:

    • ASAS 20 

      • Week 14: 59% vs 22%

      • Week 24: 56% vs 23%

    • ASAS 40 

      • Week 14: 45% vs 15%

      • Week 24: 44% vs 15%

    At week 14, treatment with Symponi 50mg ± DMARDs achieved the following median percent improvements in ASAS components vs placebo ± DMARDs, respectively:

    • Patient’s global assessment (0-10): 47% vs 13%

    • Total back pain (0-10): 50% vs 9%

    • BASFI (0-10): 37% vs -3%

    • Inflammation (0-10): 59% vs 6%

    Simponi Note

    Not Applicable

    Simponi Patient Counseling

    Patient Counseling

    Infections 

    • Inform patients that Simponi may lower the ability of their immune system to fight infections. Patients should contact their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and hepatitis B reactivation. 

    Malignancies 

    • Counsel about the risk of lymphoma and other malignancies while receiving Simponi. 

    Allergic Reactions 

    • Advise latex-sensitive patients that the needle cover on the prefilled syringe as well as the prefilled syringe in the prefilled SmartJect autoinjector contains dry natural rubber (a derivative of latex).  

    Other Medical Conditions 

    • Report any signs of new or worsening medical conditions such as congestive heart failure, demyelinating disorders, autoimmune diseases, liver disease, cytopenias, or psoriasis. 

    Instructions for Safe Administration

    • Perform the first self-injection under the supervision of a qualified healthcare professional. 

    • Prior to use, remove the prefilled syringe or the prefilled SmartJect autoinjector from the refrigerator and allow Simponi to sit at room temperature outside of the carton for at least 30 minutes and out of the reach of children.

    • Do not warm Simponi in any other way. For example, do not warm Simponi in a microwave or in hot water. 

    • Do not remove the prefilled syringe needle cover or SmartJect autoinjector cap while allowing Simponi to reach room temperature. Remove these immediately before injection. 

    • Do not pull the autoinjector away from the skin until you hear a first “click” sound and then a second “click” sound (the injection is finished and the needle is pulled back). If the autoinjector is pulled away from the skin before the injection is completed, a full dose of Simponi may not be administered. 

    • A puncture-resistant container for disposal of needles and syringes should be used. Patients or caregivers should be instructed in the technique of proper syringe and needle disposal, and be advised not to reuse these items. 

    Cost Savings Program

    Simponi Patients Support: https://www.simponi.com/

    Simponi Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Golimumab 50mg/0.5mL, 100mg/mL; soln for SC inj; preservative-free.

    Pharmacological Class

    TNF-alpha blocker.

    How Supplied

    Single-dose prefilled syringe—1; Single-dose SmartJect autoinjector—1

    How Supplied

    Simponi (golimumab) Injection is a preservative-free, sterile, clear to slightly opalescent, colorless to light yellow solution for subcutaneous use in a single-dose prefilled autoinjector (contains a prefilled glass syringe) or single-dose prefilled glass syringe. The Type 1 glass syringe has a coated stopper. The fixed stainless steel needle (5 bevel, 27G, ½ inch) is covered with a needle shield to prevent leakage of the solution through the needle and to protect the needle during handling prior to subcutaneous administration. The needle shield is made of a dry natural rubber containing latex. Simponi is supplied as follows:

    • 50 mg/0.5 mL single-dose prefilled syringe: 1 pack

    • 100 mg/mL single-dose prefilled syringe: 1 pack 

    • 50 mg/0.5 mL single-dose prefilled SmartJect® autoinjector: 1 pack 

    • 100 mg/mL single-dose prefilled SmartJect® autoinjector: 1 pack

     

    Storage

    Refrigerate Simponi at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light until the time of use. Do not freeze. Do not shake. Do not use Simponi beyond the expiration date (EXP) on the carton or the expiration date on the prefilled syringe (observed through the viewing window) or the prefilled SmartJect autoinjector.

    If needed, Simponi may be stored at room temperature up to 77°F (25°C) for a maximum single period of 30 days in the original carton to protect from light. Once a syringe or autoinjector has been stored at room temperature, do not return the product to the refrigerator. If not used within 30 days at room temperature, discard Simponi.

    Manufacturer

    Janssen Biotech, Inc.

    Generic Availability

    NO

    Simponi Indications

    Indications

    In moderately to severely active ulcerative colitis (UC) adult patients who have demonstrated corticosteroid dependence or have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine or 6-MP for: inducing and maintaining clinical response, improving endoscopic appearance of the mucosa during induction, inducing clinical remission, achieving and sustaining clinical remission in induction responders.

    Simponi Dosage and Administration

    Prior to Treatment Evaluations

    Prior to initiating Simponi and periodically during therapy, evaluate patients for active tuberculosis and tested for latent infection. Prior to initiating Simponi, patients should be tested for hepatitis B viral infection.

    Prior to initiating Simponi, consider the risks and benefits of treatment:

    • 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. 

    Test all patients for HBV infection prior to initiating Simponi.

    Consider the risks and benefits of TNF-blocker treatment, including Simponi, 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.  

    Adult

    Initially 200mg by SC inj at Week 0, followed by 100mg at Week 2, and then 100mg every 4 weeks. Rotate inj sites.

    Children

    <18yrs: not established.

    Simponi Contraindications

    Not Applicable

    Simponi Boxed Warnings

    Boxed Warning

    Serious infections. Malignancy.

    Boxed Warning

    Serious Infections

    • Increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

    • Discontinue Simponi 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. 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. 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 prior to initiating therapy in patients with chronic or recurrent infection. 

    • Monitor closely for signs and symptoms of infection during and after treatment, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

    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.

    Simponi Warnings/Precautions

    Warnings/Precautions

    Increased risk of serious or fatal infections (eg, TB, bacterial sepsis, viral, invasive fungal [treat empirically if develops], or other pathogens). Active infections: do not initiate therapy. Chronic or history of recurring or opportunistic infections. Conditions that predispose to infection. Travel to, or residence in, areas with endemic TB or mycoses. Test/treat latent TB and HBV infection prior to initiating therapy. Monitor closely if new infection, active TB (even if initial latent test is negative), reactivation of HBV, or blood dyscrasias occurs; discontinue if serious or opportunistic infection, sepsis, HBV reactivation, new or worsening CHF, hematological abnormality (eg, cytopenias), lupus-like syndrome, or serious hypersensitivity reaction develops. Malignancies. Perform periodic skin exams (esp. those with skin cancer risk factors). Prior history of dysplasia or colon carcinoma; monitor. CHF (monitor). Immunosuppression. CNS demyelinating disorders. Latex allergy. Elderly. Infants (see Interactions). Pregnancy. Nursing mothers.

    Warnings/Precautions

    Serious Infections

    • Increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. 

    • The concomitant use of a TNF blocker and abatacept or anakinra is not recommended due to a higher risk of serious infections.

    • Do not initiate 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. 

    • Prior to initiating Simponi, consider the risks and benefits of treatment:

      • 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: 

      • Monitor closely for signs and symptoms of infection during and after treatment with Simponi. 

      • Discontinue if a patient develops a serious infection, an opportunistic infection, or sepsis. 

      • If a new infection develops during treatment with Simponi: perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor them. 

    • Tuberculosis: 

      • Prior to initiating Simponi and periodically during therapy, evaluate for tuberculosis risk factors and test for latent infection.

      • Assess if treatment for latent tuberculosis is needed prior to initiating therapy; 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.

      • Monitor for 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.

    • 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.

    • Hepatitis B Virus Reactivation: 

      • Test all patients for HBV infection before initiating. If positive for hepatitis B surface antigen, consultation with an expert physician in the treatment of hepatitis B is recommended before initiating.

      • Considered risks and benefits of treatment to patients who are carriers of HBV prior to prescribing TNF blockers. 

      • For patients who are carriers of HBV and require treatment with TNF blockers: monitor closely for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.

      • Discontinue and initiate antiviral therapy with appropriate supportive treatment if HBV reactivation occurs. The safety of resuming TNF blockers after HBV reactivation has been controlled is not known. Use caution when considering resumption of TNF blockers in this situation and monitor patients closely.

    Malignancies

    • Consider the risks and benefits of TNF-blocker treatment, including Simponi, prior to initiating therapy in patients with a known malignancy other than a successfully treated nonmelanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy.  

    • Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF-blocking agents. 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. Carefully consider the potential risk with the combination of AZA or 6-MP and Simponi. 

    • Screen for dysplasia at regular intervals before therapy and throughout their disease course in 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. 

    • Carefully review the risks and benefits in patients with newly diagnosed dysplasia treated with Simponi and consider whether therapy should be continued.

    • Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

    Congestive Heart Failure

    • Simponi has not been studied in patients with a history of CHF. Use caution in patients with CHF. 

    • If a decision is made to administer Simponi to patients with CHF, monitor closely during therapy, and discontinue if new or worsening symptoms of CHF appear. 

    Demyelinating Disorders 

    • Use caution in considering the use of TNF blockers, including Simponi, in patients with central (e.g., multiple sclerosis) or peripheral (e.g., Guillain-Barré syndrome) nervous system demyelinating disorders. 

    • Consider discontinuing if these disorders develop. 

    Autoimmunity

    • Discontinue If symptoms suggestive of a lupus-like syndrome develop following treatment with Simponi.

    Use with Abatacept

    • The concomitant 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.

    • The combination of TNF blockers, including Simponi, and abatacept is not recommended.

    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. 

    • The combination of anakinra with TNF blockers, including Simponi, is not recommended 

    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. 

    Hematologic Cytopenias 

    • Caution should be exercised when using TNF blockers, including Simponi, in patients who have or have had significant cytopenias. 

    Vaccinations/Therapeutic Infectious Agents 

    • Live Vaccines: May receive vaccinations, except for live vaccines, during therapy. 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. 

    • Therapeutic Infectious Agents: Recommended to not give therapeutic infectious agents concurrently with Simponi. 

    • Non-live Vaccines: The data suggest that Simponi does not suppress the humoral immune response to the pneumococcal vaccine.

    Hypersensitivity Reactions 

    • Discontinue immediately and institute appropriate therapy if an anaphylactic or other serious allergic reaction occurs. 

    Pregnancy Considerations

    Risk Summary

    • 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.

    • Only use during pregnancy if clearly needed.  

    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. 

    • Infants may be at increased risk of infection. Administration of live vaccines to infants exposed to Simponi in utero is not recommended for 6 months following the mother’s last Simponi injection during pregnancy.

    Nursing Mother Considerations

    Risk Summary

    • There is no information regarding the presence of Simponi in human milk, the effects on breastfed infants, or the effects on milk production.

    • The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for Simponi and any potential adverse effects on the breast-fed infants from Simponi, or from the underlying maternal condition. 

    Pediatric Considerations

    Effectiveness of Simponi in pediatric patients less than 18 years of age has not been established. 

    Geriatric Considerations

    Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with Simponi.

    Simponi Pharmacokinetics

    Absorption

    Following subcutaneous administration of Simponi to healthy subjects and patients with active RA, the median time to reach maximum serum concentrations (Tmax) ranged from 2 to 6 days. A subcutaneous injection of 50-mg Simponi to healthy subjects produced a mean ± standard deviation maximum serum concentration (Cmax) of 3.2 ± 1.4 mcg/mL. 

    By cross-trial comparisons of mean AUCinf values following an IV or subcutaneous administration of Simponi, the absolute bioavailability of subcutaneous Simponi was estimated to be approximately 53%. 

    Distribution

    Following a single IV administration over the dose range of 0.1 to 10.0 mg/kg in patients with active RA, mean volume of distribution ranged from 58 to 126 mL/kg. The volume of distribution for Simponi indicates that Simponi is distributed primarily in the circulatory system with limited extravascular distribution.  

    Metabolism

    The exact metabolic pathway of golimumab is unknown. 

    Elimination

    Following a single IV administration over the dose range of 0.1 to 10.0 mg/kg in patients with active RA, mean systemic clearance of Simponi was estimated to be 4.9 to 6.7 mL/day/kg.

    Median terminal half-life values were estimated to be approximately 2 weeks in healthy subjects and patients with active RA, PsA or AS.

    Simponi Interactions

    Interactions

    Concurrent abatacept, anakinra, live vaccines, therapeutic infectious agents, or other TNF blockers: not recommended. Infants exposed to golimumab in utero: do not give live vaccines for 6 months after mother’s last inj during pregnancy. Concomitant immunosuppressants (eg, corticosteroids, MTX) may increase risk of infection. Concomitant CYP450 substrates with narrow therapeutic index (eg, warfarin, cyclosporine, theophylline); monitor and may need dose adjustments of these drugs. Caution with switching between DMARDs; overlapping may further increase the risk of infection.

    Simponi Adverse Reactions

    Adverse Reactions

    Upper respiratory tract infection, nasopharyngitis, inj site reactions, viral infections; other serious infections, malignancies (eg, melanoma, lymphoma; monitor), blood dyscrasias, new or worsening CHF, elevated liver enzymes, antibody formation, exacerbation or new onset of psoriasis.

    Simponi Clinical Trials

    Clinical Trials

    Ulcerative Colitis

    The safety and efficacy of Simponi were evaluated in 2 multicenter, randomized, double-blind, placebo-controlled clinical trials in patients ≥ 18 years of age (Trials UC-1 and UC-2). 

    Trial UC-1 was an induction trial conducted in patients with moderately to severely active ulcerative colitis (UC) who were corticosteroid dependent (i.e., an inability to successfully taper corticosteroids without a return of the symptoms of UC) or had an inadequate response to or had failed to tolerate at least 1 of the following therapies: oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine.

    Trial UC-1 was divided into 2 parts. In Part 1 (dose finding), patients were randomly assigned to 1 of 4 treatment groups: 400-mg Simponi administered subcutaneously (SC) at Week 0 and 200 mg at Week 2 (400/200 mg), 200-mg Simponi SC at Week 0 and 100 mg at Week 2 (200/100 mg), 100-mg Simponi SC at Week 0 and 50 mg at Week 2 (100/50 mg), or placebo SC at Weeks 0 and 2. In Part 2 (dose confirming), efficacy was evaluated in 761 patients who were randomly assigned to receive either 400 mg Simponi SC at Week 0 and 200 mg at Week 2, 200-mg Simponi SC at Week 0 and 100 mg at Week 2, or placebo SC at Weeks 0 and 2. Concomitant stable doses of oral aminosalicylates (5-ASA), oral corticosteroids (less than 40 mg/day), azathioprine (AZA), 6-mercaptopurine (6-MP), and/or methotrexate (MTX) were permitted. The primary endpoint was the percent of patients in clinical response at Week 6, defined as a decrease from baseline in the Mayo score by ≥ 30% and ≥ 3 points, accompanied by a decrease in the rectal bleeding subscore of ≥ 1 or a rectal bleeding subscore of 0 (no blood seen) or 1 (streaks of blood with stool less than half the time).

    Trial UC-2 was a randomized-withdrawal maintenance trial that evaluated 456 patients who achieved clinical response with Simponi induction and tolerated Simponi treatment. Patients were randomly assigned to receive Simponi 50 mg, Simponi 100 mg or placebo administered subcutaneously every 4 weeks. Patients were permitted to receive concomitant stable doses of oral aminosalicylates, azathioprine, 6-mercaptopurine, and/or methotrexate. Corticosteroids were to be tapered at the start of the maintenance trial. The primary endpoint was the percent of patients maintaining clinical response through Week 54.

    The following results from Trial UC-1 showed that a greater proportion of patients in the Simponi 200mg/100mg group achieved clinical response, clinical remission, and had improvement of endoscopic appearance of the mucosa at week 6 compared with the placebo group, respectively:

    • Clinical response: 51% vs 30% (treatment difference, 21%; 95% CI, 12-29; P <.0001)

    • Clinical remission: 18% vs 6% (treatment difference, 11%; 95% CI, 6-17; P <.0001)

    • Improvement of endoscopic appearance of the mucosa: 42% vs 29% (treatment difference, 14%; 95% CI, 5-22; P =.0014)

    The following results from Trial UC-2 showed that a greater proportion of patients in the Simponi 100mg group achieved clinical response through week 54 and clinical remission at both week 30 and week 54 compared with the placebo group, respectively:

    • Clinical response: 50% vs 31% (treatment difference, 19%; 95% CI, 8-29; P <.001)

    • Clinical remission: 28% vs 16% (treatment difference, 12%; 95% CI, 3-21; P =.004)

    Simponi Note

    Not Applicable

    Simponi Patient Counseling

    Patient Counseling

    Infections 

    • Inform patients that Simponi may lower the ability of their immune system to fight infections. Patients should contact their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and hepatitis B reactivation. 

    Malignancies 

    • Counsel about the risk of lymphoma and other malignancies while receiving Simponi. 

    Allergic Reactions 

    • Advise latex-sensitive patients that the needle cover on the prefilled syringe as well as the prefilled syringe in the prefilled SmartJect autoinjector contains dry natural rubber (a derivative of latex).  

    Other Medical Conditions 

    • Report any signs of new or worsening medical conditions such as congestive heart failure, demyelinating disorders, autoimmune diseases, liver disease, cytopenias, or psoriasis. 

    Instructions for Safe Administration

    • Perform the first self-injection under the supervision of a qualified healthcare professional. 

    • Prior to use, remove the prefilled syringe or the prefilled SmartJect autoinjector from the refrigerator and allow Simponi to sit at room temperature outside of the carton for at least 30 minutes and out of the reach of children.

    • Do not warm Simponi in any other way. For example, do not warm Simponi in a microwave or in hot water. 

    • Do not remove the prefilled syringe needle cover or SmartJect autoinjector cap while allowing Simponi to reach room temperature. Remove these immediately before injection. 

    • Do not pull the autoinjector away from the skin until you hear a first “click” sound and then a second “click” sound (the injection is finished and the needle is pulled back). If the autoinjector is pulled away from the skin before the injection is completed, a full dose of Simponi may not be administered. 

    • A puncture-resistant container for disposal of needles and syringes should be used. Patients or caregivers should be instructed in the technique of proper syringe and needle disposal, and be advised not to reuse these items. 

    Cost Savings Program

    Simponi Patients Support: https://www.simponi.com/

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