Golimumab (Simponi) is a human monoclonal antibody that acts as an anti-inflammatory drug by inhibiting tumor necrosis factor-alpha. It is used to treat the following conditions:

• Adults with Ankylosing spondylitis as monotherapy or in combination with methotrexate.
• Adult patients with psoriatic arthritis as monotherapy or in combination with methotrexate.
• Adults with moderately-to-severely active rheumatoid arthritis as monotherapy or in combination with methotrexate.
• Adults with moderately-to-severely active ulcerative colitis who have an inadequate response to oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine (Golimumab may induce and maintain clinical response, improve mucosal appearance, and induce and sustain remission in patients unresponsive to first-line of therapies)
• Off-Label Use of Golimumab includes axial active non-radiographic spondyloarthritis.

Golimumab (Simponil) Dose in Adults

Note: Patients may be continued on non-biological DMARDs or corticosteroids while being treated with golimumab. However, it should not be given in combination with biological DMARDs.

Golimumab Use in the treatment of Ankylosing spondylitis:

• 2 mg/kg intravenous at weeks 0, 4, followed by 8 weekly thereafter as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.
• 50 mg subQ once a month as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.

Golimumab Use in the treatment of Psoriatic arthritis:

• 2 mg/kg intravenous at weeks 0 and 4, followed by 8 weekly thereafter as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.
• 50 mg subQ once a month as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.

Golimumab Use in the treatment of Rheumatoid arthritis:

• 2 mg/kg intravenous at weeks 0 and 4, followed by 8 weekly thereafter in combination with methotrexate or
• 50 mg subQ once a month in combination with methotrexate.

Golimumab Use in the treatment of Ulcerative colitis:

• Induction: 200 mg subQ at week 0 and 100 mg at week 2
• Maintenance therapy: 100 mg every 4 weeks.

Off label use in the treatment of active (non-radiographic) Axial spondyloarthritis:

• 50 mg subcutaneous once every 4 weeks for 16 weeks.

Use in Children:

Safety and efficacy not established in children.

Golimumab Pregnancy Risk Factor B

• Monoclonal antibodies that cross the placental boundary during the third trimester may be found in newborn serum for up to six month.
• Golimumab is more dangerous for children who are exposed in utero.
• Additionally, live vaccines should not be administered to newborns until six months after the last maternal dose.
• Its use in pregnancy is not known.

Golimumab use during breastfeeding:

• IgG can be found in breastmilk. 
• Manufacturers recommend weighing the benefits and risks of treating the mother, as well as exposing the baby to the drug.

Golimumab Use in Kidney disease:

The manufacturer has not recommended any dose adjustment in patients with renal disease (It has not been studied in patients with renal disease).

Golimumab Use in Liver disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease (It has not been studied in patients with liver disease).

Common Side Effects of Golimumab:

• Hematologic & oncologic:

  • Positive ANA titer

• Immunologic:

  • Antibody development

• Infection:

  • Infection

• Respiratory:

  • Upper respiratory tract infection

Less Common Side Effects of Golimumab Include:

• 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

Side effects of Golimumab (Frequency not defined):

• Dermatologic:

  • Cellulitis

• Infection:

  • Sepsis

• Respiratory:

  • Tuberculosis

Contraindications to Golimumab:

There are no contraindications for its use, according to the manufacturer.

Canadian labeling:

• Allergy reactions to golimumab or latex or any other ingredient in formulation or packaging
• Patients with severe infections such as sepsis and tuberculosis or opportunistic diseases
• Moderate to severe (NYHA Class III/IV) heart disease

Warnings and Precautions

• Autoimmune disorder:

  • Other autoimmune disorders, such as Lupus-like Syndrome and Positive Antinuclear Antibody Titers, can also be developed by patients.
  • Patients with symptoms should stop taking therapy.

• Demyelinating disease:

  • Patients with a history of demyelinating diseases should not use it.
  • It has been associated with demyelinating conditions such as multiple sclerosis and optic neuritis.

• Heart failure:

  • It is possible for patients to develop symptoms of cardiac failure, or worsen their symptoms.
  • Heart failure symptoms should be closely monitored in patients with left ventricular dysfunction and underlying ischemic cardiac disease.

• Hematologic effects

  • Patients with underlying hematological conditions like anemia or thrombocytopenia should not use it. Treatment should be stopped for patients suffering from severe cytopenia.
  • Aplastic anemia, neutropenia and thrombocytopenia are all possible signs of severe cytopenia.

• Hepatitis B:

  • Before starting therapy, patients should be tested for Hepatitis A. Screening should include HBsAg, hepatitis B's surface antigen (anti-HBc) and Hepatitis B's core antibody (anti–HBc).
  • Anti-HBc testing should include both IgG antibodies and IgM antibodies. Isolated IgM antibodies against HBc are not recommended as this only indicates recent infection.
  • All patients with viral hepatitis must be treated with the appropriate antiviral therapy. Patients with a history of infection, as indicated by positive anti-HBc antibody tests, should be treated with prophylactic antiviral treatment.
  • American society for clinical oncology recommends that patients with HBsAg or anti-HBc positivity be initiated on prophylactic antiviral therapy.
  • Patients with HBsAg-negative and anti-HBc-positive status should be closely monitored for HBV reactivation by HBV DNA and ALT testing at least every three months.
  • After discontinuing golimumab, the patient should be closely monitored for several months.

• Hypersensitivity reactions

  • Hypotension, angioedema and rash may be signs of allergic reactions.
  • These patients should be stopped from receiving therapy and treated accordingly.
  • Symptoms of allergic reactions can occur either during therapy or within an hour after the infusion.

• Infections [US Boxed Warning]

  • Golimumab can make the patient more susceptible to serious infections, which could lead to death or hospitalization.
  • Patients who are taking other immunosuppressants concurrently have a higher risk of getting infected.
  • Patients who receive TNF inhibitors, including golimumab, may develop active tuberculosis. They could also experience invasive fungal infections such as blastomycosis or coccidioidomycosis.
  • The spread of infection may be more severe.
  • Testing for antigen or antibodies may give false-negative results.
  • Patients suffering from serious infections should be advised to stop taking TNF inhibitors. Patients with recurrent infections must also be stopped from receiving TNF inhibitors.
  • Patients at higher risk for developing the infection may need to be treated immediately with antifungal medication.
  • Patients with concomitant immunosuppressants, elderly patients, patients from areas endemic to mycosis, those with diabetes and patients who have been exposed to tuberculosis should not use it.

• Malignancy[US Boxed Warning]

  • TNF-blocking drugs can increase the incidence of lymphoma, and other malignancies.
  • The effect of golimumab upon malignancy incidence is unclear because the patients were taking a combination immunosuppressants.
  • Patients with Rheumatoid Arthritis also have a higher incidence of lymphoma. It is unclear what role golimumab played in the development and progression of lymphoma.
  • Young adults and adolescents who have received TNF-blocking drugs and concurrent or previous azathioprine, mercaptopurine to treat ulcerative colitis or Crohn’s colitis are at higher risk of developing hepatosplenic T cell lymphoma.
  • TNF-blocking drugs such as golimumab have been linked to melanoma or Merkel cell carcinoma. 
  • A periodic skin exam should be done on patients undergoing therapy, especially those who are at high risk.

• Tuberculosis [US Boxed Warning]

  • It has been reported that it can cause reactivation of latent tuberculosis or new infections in the lungs, disseminated, and extrapulmonary tuberculosis.
  • Before starting therapy, it is important to perform skin tests for tuberculin.
  • Before starting treatment, patients with latent tuberculosis must be treated.
  • Patients living in endemic areas should be monitored for the possibility of contracting the infection.
  • Tuberculosis patients should not be treated if they have not completed the entire course of anti-tuberculous treatment.
  • Patients who have had previous exposure to tuberculosis must be warned about the dangers of taking this drug.

Golimumab: Drug Interaction

Monitoring Parameters:

• CBC with differential counts
• Screen for latent TB prior to initiating and periodically during therapy
• Hepatitis B virus screening prior to initiating therapy in all patients, during the treatment, and for several months after the therapy in patients who are HBV carriers
• Monitor for clinical response and assess for the improvement in the functional status.
• Monitor for the clinical features of infection prior to, during, and following therapy
• Monitor for clinical features of allergic reactions
• Observe the patients with ischemic heart disease for clinical features and worsening symptoms of heart failure.
• Observe the patient for symptoms of the lupus-like syndrome
• Monitor the patient for clinical features of malignancy like splenomegaly, hepatomegaly, abdominal pain, fever, night sweats, weight loss, and skin examination

How to administer Golimumab?

• Intravenous administration:
  • Dilute the drug prior to its use.
  • Infuse over at least half an hour, using an infusion set with an in-line low protein-binding 0.22-micron filter.
  • Avoid infusing it in the same line with other medications.
• Subcutaneous injection:
  • Hold the autoinjector firmly against the skin and inject subcutaneously into the lower abdomen below the nave, the thigh, or the upper arm.
  • A loud click is heard when the injection has begun.
  • Hold the autoinjector against the skin until the second click is heard which may take 3 - 15 seconds.
  • Following the second click, lift the autoinjector from the injection site.
  • Do not inject into red, scaly, hard, tender, bruised skin, and areas with scars and stretch marks.
  • Rotate the injection sites.
  • Multiple injections should be administered at different sites on the body.

Mechanism of action of Golimumab:

• It is a monoclonal antibody for humans that inhibits TNFa (tumor-neoplasm alpha) activity by binding human tumor necrosis factor (TNFa).
• The following inflammatory processes can be inhibited by blocking TNFa activity:
  • Induction of proinflammatory cytokines (interleukin-6, IL-8, Granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor)
  • For leukocyte infiltration, adhesion molecules are required for expression (E-selectin and vascular cell adhesion mole [VCAM]-1, and intercellular adhesion mole [ICAM]-1).
  • Activation and maintenance of neutrophils.

It has been abioavailabilitySubcutaneous administration of the drug results in a reduction of approximately 53% 

TheMetabolicThe pathway is unknown and it is unclear what the implications are.

half-life eliminationIt takes approximately 2 weeks. Subcutaneous administration takes 2-6 days to reach peak serum concentration.

International brand Names of Golimumab:

• Simponi
• Simponi IV

Golimumab Brand Names in Pakistan:

No brands available in Pakistan