Simponi (Golimumab) is a TNF (tumor necrosis factor) inhibitor. It reduces the inflammatory process by reducing the production of IL-6 and IL-8. It is used to treat inflammatory conditions like rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis.

Indications of Golimumab:

• Ankylosing spondylitis (Simponi, Simponi Aria):

  • It is used for the treatment of adults with active ankylosing spondylitis (single agent or concurrently with methotrexate).

• Psoriatic arthritis (Simponi, Simponi Aria):

  • It is indicated for the treatment of adults with active psoriatic arthritis (monotherapy or in combination with methotrexate).

• Rheumatoid arthritis (Simponi, Simponi Aria):

  • It is effective for the treatment of adults with moderately-to-severely active rheumatoid arthritis (concurrently with methotrexate).

• Ulcerative colitis (Simponi):

  • In adults with moderately-to-severely active ulcerative colitis with corticosteroid dependence, refractory, intolerant to oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine (to induce and maintain clinical response, improve mucosal appearance during induction, induce clinical remission, and achieve and sustain remission in induction responders), it is an effective therapy.

• Off Label Use of Golimumab in Adults:

  • Axial spondyloarthritis (active, nonradiographic)

Read: Simponi Vs Enbrel

Golimumab (Simponi) dose in adults:

Note: Corticosteroids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and/or NSAIDs may be continued for the treatment of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. Golimumab should not be used in combination with biologic DMARDs.

Simponi Dose in the treatment of Ankylosing spondylitis:

• IV: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter (monotherapy or in combination with methotrexate or other nonbiologic DMARDs).
• SubQ: 50 mg once every 4 weeks (monotherapy or in combination with methotrexate or other nonbiologic DMARDs)

Simponi Dose in the treatment of Psoriatic arthritis:

• IV: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter (monotherapy or in combination with methotrexate or other nonbiologic DMARDs).
• SubQ: 50 mg once every 4 weeks (monotherapy or in combination with methotrexate or other nonbiologic DMARDs).

Simponi Dose in the treatment of Rheumatoid arthritis:

• IV: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter (in combination with methotrexate).
• SubQ: 50 mg once every 4 weeks concurrently with methotrexate).

Simponi dose in the treatment of Ulcerative colitis:

• SubQ: Induction: 200 mg at week 0, then 100 mg at week 2.
• maintenance therapy: 100 mg every 4 weeks.

Simponi Dose in the treatment of Axial spondyloarthritis (active, non-radiographic) (off-label):

• SubQ: 50 mg once every month for 16 weeks.

Use in Children:

Not indicated.

Pregnancy Risk Category: B

• No adverse reactions were found in animal reproduction studies. There are limited data available on the effects of golimumab during pregnancy.
• Monoclonal antibodies can cross the placenta during the third trimester.
• Data from other TNF-blockers suggests that newborn serum could contain antibodies for as long as 6 months.
• Infants who are exposed to golimumab during pregnancy have a high risk of contracting infection.
• Live vaccines for newborns should not be administered until six months after the last maternal dose.

Golimumab use during breastfeeding:

• Golimumab secretion is not known in breast milk.
• Breast milk contains maternal IgG.
• The manufacturer will inform you about the risks to infants and the benefits to breastfeeding.

Dose adjustment in renal disease:

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Common Side Effects of Simponi (Golimumab):

• Hematologic & Oncologic:

  • Positive ANA Titer

• Immunologic:

  • Antibody Development

• Infection:

  • Infection

• Respiratory:

  • Upper Respiratory Tract Infection

Rare Side Effects Of Simponi (Golimumab):

• Cardiovascular:

  • Hypertension

• Central Nervous System:

  • Dizziness
  • Paresthesia

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Constipation

• Hematologic & Oncologic:

  • Decreased Neutrophils
  • Leukopenia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Infection:

  • Viral Infection
  • Fungal Infection
  • Bacterial Infection

• Local:

  • Injection Site Reaction

• Respiratory:

  • Nasopharyngitis
  • Bronchitis
  • Sinusitis

• Miscellaneous:

  • Fever
  • Infusion-Related Reaction

Simponi Side effects (Frequency Not Defined):

• Dermatologic:

  • Cellulitis

• Infection:

  • Sepsis

• Respiratory:

  • Tuberculosis

Contraindications to Simponi (Golimumab):

The US labeling of the manufacturer does not list any contraindications. Canadian labeling:

• Hypersensitivity to golimumab or latex or any other ingredient of formulations or packaging
• Severe infections (eg sepsis or tuberculosis, or opportunistic infection)
• Moderate to severe heart disease (NYHA class III/IV).

Warnings and precautions

• Autoimmune disorder:

  • Patients with low baseline levels of antinuclear antibodies have had positive titers.
  • Rarely are autoimmune conditions such as Lupus-like Syndrome or lupus-like Syndrome.
  • Monitoring is necessary on a regular basis
  • If symptoms persist, it is best to stop therapy.

• Demyelinating disease:

  • Golimumab may cause demyelinating disorders such as multiple sclerosis and optic neuritis. It can also cause Guillain Barre syndrome, optic neuritis and polyneuropathy.
  • Therapy should be stopped for patients suffering from peripheral or CNS demyelinating disorders.
  • It should not be used in patients suffering from pre-existing or new-onset peripheral or central nervous system demyelinating conditions.

• Heart failure:

  • Golimumab and other TNF-blockers have been shown to worsen and cause new-onset heart disease.
  • With the onset of or worsening symptoms, strict monitoring and withdrawal may be required.
  • Extreme caution is advised for patients suffering from reduced left ventricular function/heart failure.
  • As per AHA, TNF blockers have been shown to increase myocardial dysfunction or cause myocardial toxicity.

• Hematologic effects

  • TNF-blockers can cause pancytopenia and other significant cytopenias.
  • Golimumab may cause pancytopenia and leukopenia as well as neutropenia and thrombocytopenia.
  • Therapy should be stopped if there are any significant hematologic abnormalities.
  • Extreme caution is required for patients with underlying hemologic disorders.

• Hepatitis B:

  • Patients who are taking immunosuppressants concurrently can experience reactivation, which could be potentially life-threatening.
  • Before beginning therapy, it is important to check your HBV status.
  • Patients with positive HBV-surface antigens should be referred to hepatitis B treatment/evaluation before going on to golimumab therapy.
  • After stopping golimumab treatment, HBV carriers must be monitored for signs and symptoms of active infection for several months.
  • If there is a reactivation of the virus, it is important to stop therapy and start antiviral therapy.
  • If therapy is to be resumed, extreme caution and close monitoring are necessary.

• Hypersensitivity reactions

  • Administration of I/V/S/C can cause severe systemic hypersensitivity reactions, including anaphylaxis, which may present with dyspnea and hives, nausea, pruritus, and vomiting.
  • You may experience reactions within one hour after IV infusion.
  • If you have signs or symptoms, stop therapy immediately and get the appropriate treatment.

• Infections [US Boxed Warning]

  • Patients who receive golimumab have a higher risk of serious reactions.
  • Patients who are taking immunosuppressive drugs (eg, corticosteroids or methotrexate) concurrently are more at risk for infection.
  • Patients who have taken golimumab or TNF blockers are more likely to develop active tuberculosis.
  • Patients with active infection might show negative histoplasmosis tests (antigen, antibody)
  • Signs and symptoms of infection require close monitoring.
  • Stop therapy if you have a serious infection or sepsis.
  • Patients with a history or recurrent chronic infection should not use it.
  • Patients at high risk of invasive fungal infections and who have severe systemic illnesses should receive empirical antifungal treatment.
  • Caution should be exercised (consider risks versus benefits) when considering use in the elderly, patients taking concomitant immunosuppressants, patients with chronic or recurrent infection, patients who have been exposed to tuberculosis, patients with a history of opportunistic infection, patients with comorbid conditions that predispose them to infections (eg, diabetes), or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis).patients with an active infection, including localized infection, which is clinically important.
  • Patients who get a new infection during treatment should not receive therapy.

• Malignancy: [US Boxed Warning]

  • TNF-blockers are known for causing lymphoma, other malignancies that could be life-threatening.
  • Half of all malignancies in children were lymphomas, both Hodgkin or non-Hogkin. Other cases included rare malignancies that are not usually found in this population.
  • Malignancy began after 30 months, with a range of 1 to 84 month after the TNF-blocking medication was started. Patients who were also taking immunosuppressants had the most cases.
  • Patients with rheumatoid arthritis are at greater risk for lymphoma.
  • TNF-blockers have been shown to cause hepatosplenic T cell lymphoma (HSTCL), a rare form of T-cell lymphoma.
  • Young adult males with Crohn disease, ulcerative colitis and who have been treated with TNF-blocking agents and concurrent or previous azathioprine and mercaptopurine may be at increased risk.
  • TNF-blockers can cause Merkel cell carcinoma and melanoma.
  • Patients at higher risk for cancer should undergo skin examinations on a regular basis.
  • Patients with a diagnosed malignancy should weigh the risks and benefits. If a patient develops a malignancy, consider whether continuing treatment is possible.

• Tuberculosis: [US-Boxed Warning]

  • Patients should be tested for tuberculosis risk factors (with a tuberculin test) before and during treatment.
  • Tuberculosis can develop in patients who have received golimumab. This includes reactivation or new infection as well as pulmonary tuberculosis.
  • Latent tuberculosis must be treated before therapy can begin.
  • Patients with first negative tuberculin skin test, patients receiving treatment for latent or active tuberculosis should be monitored for the possibility of developing tuberculosis.
  • Therapy should be administered with caution in areas where tuberculosis has become an epidemic.
  • Anti-tuberculosis treatment may be considered if a course of treatment is not possible for patients with a history or risk factors of active or latent tuberculosis.
  • Before starting treatment for patients who have been exposed, it is important to properly evaluate the patient.

Monitoring parameters:

• CBC with differential
• latent TB screening (prior to initiating and periodically during therapy)
• HBV screening (prior to initiating [all patients]; during and for several months following therapy [HBV carriers])
• Monitor improvement of symptoms and physical function assessments
• Signs/symptoms of infection (before, during, and after therapy)
• Signs/symptoms/worsening of heart failure
• Symptoms of hypersensitivity reaction
• Symptoms of a lupus-like syndrome
• Signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) including periodic skin examination

How to administer Simponi (Golimumab)?

Note: The safety and efficacy of switching between the IV and SubQ formulations and routes have not been studied.

IV:

• Dilution is necessary before use.
• The infusion should be over 30 minutes, using an infusion set with an in-line low protein binding 0.22 micron filter.
• The same line should not be infused with other medications.

Subcutaneous injection:

• Hold autoinjector firmly against the skin and inject subcutaneously into the thigh, lower abdomen (below the navel), or upper arm.
• When the injection is started, a loud click will be heard. It should be continued to hold against the skin until the second click is heard (may take 3 to 15 seconds).
• The autoinjector from the injection site should be lifted after the second click.
• Injection sites should be rotated and injecting should be avoided into tender, red, scaly, hard, or bruised skin, or areas with scars or stretch marks.
• If multiple injections are required for a single dose, administer the drug at different sites on the body.

Mechanism of action of Golimumab (Simponi):

• Golimumab, a monoclonal human antibody that binds to human tumor necrosis factors-alpha (TNFa) and interferes with endogenous TNFa activities, is called a human monoclonal antibody.
• Biological activities of TNFa include the induction of proinflammatory cytokines (interleukin [IL]-6, IL-8, Granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor), expression of adhesion molecules (E-selectin, vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1) necessary for leukocyte infiltration, activation of neutrophils and eosinophils.

Distribution:

• Distributed primarily to the circulatory system with limited extravascular distribution.

Bioavailability:

• SubQ: ~53%

Metabolism:

• Pathway unknown

Half-life elimination:

• About 2 weeks

Time to peak, serum:

• SubQ: 2-6 days

International Brand Names of Golimumab:

• Simponi
• Simponi Aria
• Simponie

Golimumab Brand Names in Pakistan:

No Brands Available in Pakistan.