Golimumab - Uses, Dosage, Side Effects, Precautions, Warnings, and Interactions

Overview:

Golimumab is a TNF (tumor necrosis factor)- alpha-inhibiting biological monoclonal-antibody medicine. It treats rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. It is a drug approved by the Food and Drug Administration (FDA) on April 24, 2009. The drug is not a painkiller but has an effect in controlling the effects of rheumatoid arthritis.

How Does Golimumab Work?

Golimumab is a drug that blocks the action of the cytokine TNF-alpha. The TNF-alpha plays an important role in the inflammatory process. It is released due to inflammation in joints and bones in rheumatoid arthritis. Hence, the ultimate effect of Golimumab in arthritis patients is inhibiting the TNF-alpha and controlling inflammation, cartilage, and bone destruction.

Uses:

Golimumab is used in treating certain autoimmune conditions (conditions that have weakened immunity and start producing antibodies against the body's healthy cells). The following are some of its uses:

• Rheumatoid Arthritis: It is an autoimmune disease caused due to production of antibodies against the joints leading to pain and swelling. In moderate to severe cases, Golimumab, along with Methotrexate (immunosuppressant), is effective.

• Psoriatic Arthritis: A type of arthritis that causes joint pain and red patches with silvery scales on the skin. It is often associated with psoriasis. This drug is also effective in combination with Methotrexate.

• Ankylosing Spondylitis: It causes pain in the spine and leads to the fusion of the spine's bones. The drug alone, without any adjunct, is effective in providing treatment.

• Ulcerative Colitis: A condition that occurs due to inflammation and ulcers in the digestive tract. Golimumab is indicated in these individuals when all other medications have failed to provide relief.

• Polyarticular Juvenile Idiopathic Arthritis: A type of arthritis that occurs in kids and teenagers.

Dosage and Administration:

Golimumab is administered in an injection form through the subcutaneous (below the skin) or intravenous route. It is usually available as a pre-filled syringe containing 50 milligrams of the drug. It is given once every four weeks. Whereas in ulcerative colitis, it is given once initially in the first week, followed by a dose the week after that. Later, the usual dose of once every four weeks is maintained. When the intravenous route is used, the nurse or the doctor injects the drug for 30 minutes. The pre-filled syringe form can be self-injected, but a nurse or health professional does the intravenous administration in a hospital setting.

Warnings and Precautions:

The drug has the following warnings from the Food and Drug Administration:

• Infection: Golimumab reduces the effect of the immune system and makes the body more prone to infections. The individuals on this drug develop infections such as tuberculosis (TB) and other bacterial, viral, and fungal infections. Before the doctor prescribes the drug, a detailed history regarding the presence of infectious diseases is noted. A TB test is performed before starting the drug. Even if the patient gets a negative result for TB, the doctor checks for any symptoms at regular intervals before, during, and after the treatment with Golimumab.

• Malignancy or Cancer: Patients on Golimumab medication have an increased risk of developing lymphoma (cancer of the lymphatic system) and other types of cancer. People under 18 years of age and those with the active form of the disease are more likely to develop cancer.

• Decreased Blood Cell Count: The drug can affect the levels of different blood cells leading to anemia, infection, and bleeding disorders. Any history regarding lowered blood cell count must be informed to the doctor.

• Heart Failure: Patients with a history of heart failure must inform the doctor. The drug will cause heart failure or has the ability to worsen the condition.

• Hepatitis B: The doctor tests for the presence of the hepatitis B virus in the body before initiating the treatment. The drug activates the virus if present in the body and causes liver damage. So, a complete history must be recorded, and the test for hepatitis B virus must be performed before, during, and after the treatment.

• Rubber and Latex Allergy: Since the covering of the pre-filled syringe contains latex, any allergy to latex must be discussed with the doctor before the treatment.

Infection and malignancy are the most dangerous warnings that can cause serious effects on the body. The doctor must collect all necessary history and perform tests before starting the medication to prevent further complications.

Drug Interactions:

A drug interaction occurs when two drugs that have an effect on each other are used. The resulting effect would be related to decreasing or increasing the effectiveness of the medication. Drug interactions are avoided by not combining their use with the other drug, changing its dosage, or taking certain precautionary measures. The following are the drugs that interact with Golimumab:

• Abatacept.

• Abciximab.

• Acyclovir.

• Albendazole.

• Adenovirus type 7 vaccine.

• Alfentanil.

• Aminophylline.

• Anakinra.

• Ansuvimab

• Apremilast.

• Arsenic trioxide.

• Rituximab.

• Betamethasone.

• Bleomycin.

• Budesonide.

• Cemiplimab.

• Chloramphenicol.

• Cisplatin.

• Dactinomycin.

• Diroximel fumarate.

• Filgotinib.

• Fludrocortisone.

• Ibalizumab.

• Methylprednisolone.

• Natalizumab.

• Oxaliplatin.

• Penicillamine.

• Quinestrol.

• Satralizumab.

• Teriflunomide.

• Upadacitinib.

• Vedolizumab.

• Zidovudine.

A few examples of live vaccines avoided for patients under Golimumab therapy are

• Measles, mumps, and rubella vaccine.

• Live flu vaccine.

• Varicella vaccine.

• Herpes zoster vaccine.

• Typhoid vaccine.

• Smallpox vaccine

The drugs mentioned above and vaccines have been reported to cause interaction with Golimumab. Other additional drugs may also be involved in causing drug interaction that differs from one patient to another. Food interaction with the drug has not been reported to date.

For Patients:

What Is Rheumatoid Arthritis?

Rheumatoid arthritis is an autoimmune condition leading to the inflammation of the joints. In a healthy human body, the immune system tries to attack foreign agents such as bacteria, viruses, fungi, or any organism. But in the case of rheumatoid arthritis, the immune system attacks the healthy joints within the body and causes damage. The reason for the autoimmunity developed in these individuals is not clearly understood. Here, the inflammatory process at the joints is caused due to the activation of two crucial inflammatory cytokines:

• Interleukin-1 (IL-1): It plays a significant role in bone and cartilage destruction but has no role in joint inflammation and swelling.

• Tumor Necrosis Factor Alpha: An immune system protein that causes inflammation and symptoms in rheumatoid arthritis.

Effects of Rheumatoid Arthritis:

Rheumatoid arthritis commonly affects the joints of the hand, wrist, and knees. It can also affect many joints at a time, causing polyarthritis. The affected joint tissue gets inflamed, leading to damage, persistent pain, and lack of balance. It also affects other tissues in the body, such as the heart, lungs, and eyes.

Learn More About Golimumab:

When Does a Doctor Start Treatment With Golimumab?

The treatment for rheumatoid arthritis is usually started with steroids and Methotrexate. The following alternate effective drugs are chosen if the symptoms persist after the initial therapy. The doctor checks the patient's condition and performs lab or imaging tests if necessary to find the cause for treatment failure and suggests a new treatment plan. The doctor starts treatment with medications like Golimumab. Since it has a blocking effect on the TNF-alpha, inflammation and joint pain can be effectively controlled.

Effectiveness of Golimumab:

Golimumab effectively treats rheumatoid arthritis by providing the following effects:

• Pain relief in one to three months after starting the medication.

• Decreases joint pain and swelling.

• Lowers the progression rate of rheumatoid arthritis.

• Relieves discomfort and improves the daily activities of the patient.

Things to Inform the Doctor Before Starting Golimumab:

Before starting any medical therapy, a complete history regarding the past or present medical treatment, allergy, and underlying medical conditions is discussed with the physician. The patient must share the following history with the doctor:

• History of infections or symptoms like fever, chills, cough, difficulty breathing, unexplained weight loss, painful skin lesions, stomach ache, vomiting, diarrhea, muscle pain, blood in the phlegm, painful urination, frequent urination, feeling more tired than usual, or history of treatment for infections.

• History of tuberculosis or any recent contact with a tuberculosis patient.

• History of past or present autoimmune conditions of the patient, such as diabetes, HIV (human immunodeficiency virus).

• History of any diseases related to the heart or surgery done for heart problems.

• History of liver diseases such as hepatitis.

• Recent travel to certain countries with high chances of getting infected with histoplasmosis, blastomycosis, coccidioidomycosis, or other fungal infections.

• Allergy history to food substances, drugs, or latex material.

• History regarding medications taken for other conditions in the past.

• Pregnancy history is also noted if the mother is pregnant or breastfeeding.

• History of any medications taken in the past for rheumatoid arthritis which failed in providing relief.

Starting With Golimumab:

How to Take Golimumab?

Golimumab is usually available as a pre-filled syringe or in self-injection form. The doses may vary for each patient depending on their condition, age, severity, underlying medical illness, and reaction to the first dose.

• Dosage for Rheumatoid Arthritis in Children: The dosage for children between 0 to 17 years old has still not been estimated.

• Dosage for Rheumatoid Arthritis in Adults: Adults above 18 years are given 50 milligrams of the drug in an injectable form. The drug is administered once every month. The drug is usually given in combination with Methotrexate.

Things to Know After Starting Treatment with Golimumab:

The following things to be kept in mind after starting treatment with Golimumab:

• Storage: The drug is kept in a refrigerator at two degrees Celsius to eight degrees Celsius. If the drug is at room temperature, it should not be returned to the refrigerator. Do not expose the drug to extreme heat and cold temperatures. The drug should not be used if it is frozen.

• Refills: The medication can be refilled, and the doctor writes the number of refills in the prescription, which can be used while purchasing from the pharmacy.

• Travel: If travel has been scheduled during treatment, always remember to carry the drug. The pre-filled injection form stays at a cool temperature and is helpful while traveling. Never leave the medication inside the car, as it can bring down the temperature due to the heat.

Side Effects:

The side effects of Golimumab are:

• Allergic reactions may occur at the injection site. Pain, redness, swelling, itching, and tingling sensation at the injection site indicate an allergic reaction.

• Upper respiratory tract infections such as runny nose, sore throat, and hoarseness of voice.

• Viral infections like flu and cold sores.

• A persistent cough that does not go away.

• Fever.

• Continuous weight loss due to unknown causes.

• A rash on the face and arms worsens on exposure to sunlight.

• Symptoms of cancer include fever, tiredness, weight loss, overgrowth on skin surfaces, changes in appearance, and growth of lumps on the face, neck, and back.

• Symptoms of heart failure include shortness of breath, tiredness, increased weight, and swollen legs.

• Sometimes, an allergic reaction to the drug may need a shift to any other treatment modality. In a few other cases, there may be no progress in the patient even after regular medication consumption.

Apart from the side effects listed above, the patient can also experience other symptoms. Any changes noticed must be consulted with the doctor immediately to start the appropriate management.

Dietary Alterations:

No dietary alterations are usually required. A normal healthy diet can be maintained. Any modifications in the diet, if needed, will be discussed by the doctor before starting the treatment.

What Should Be Done When a Dose Is Missed?

Sometimes, the individual forgets to take the medication. In such cases, patients must take the missed dose as soon as they remember. If the patient remembers that the dose has been missed when nearing the next dose, the missed dose is skipped, and the next dose alone is taken. This is to prevent double dosage at that particular month which can lead to side effects due to overdosage.

• If the missed dose is two weeks late, the drug can be administered.

• If the missed dose is late by more than two weeks, the patient can inject the missed dose and formulate a new schedule with the doctor’s consent.

What Should Be Done to Treat Golumimab Overdose?

Single doses up to 10 mg/kg have not been proven to cause any symptoms of overdosage. If any symptoms occur, the patient must inform the doctor, and the necessary treatment can be done.

How to Self-Administer Golimumab?

The doctor suggests self-administering the drug after a few days. Until then, the health professional injects the drug and teaches the patient how to inject it themselves. The following are a few steps to be followed by the patient during self-administration of the drug:

• The drug is first placed at room temperature for about half an hour, and the color of the solution is checked. The drug is discarded if any discoloration or presence of foreign objects is noticed. It is normally clear to light yellow in color.

• The injection site is cleaned with alcohol wipes or a sterile solution.

• An autoinjector is placed on the injection site and allowed to stay in that position till the whole solution is injected. It usually takes about 15 seconds to deposit the solution completely.

• Do not use the same injection site for all the doses. The various sites of injection are in front of the thigh or the area below the belly button.

Dispose of Golimumab:

The used syringes with needles must not be disposed of with the usual domestic waste. The patient can purchase a puncture-proof disposal container and discard them separately. The container is labeled ‘ do not recycle’ before throwing it away into the trash.

Monitoring of the Patient:

The doctor monitors the presence of tuberculosis and hepatitis in the patient from time to time to prevent any unfavorable complications. The doctor runs a series of tests before, during, and after treatment to check for signs of tuberculosis, hepatitis B, and other infections.

Avoid Self-Medication:

Never take any medicine, including Golimumab, unless prescribed by a registered healthcare provider. All the blood tests mentioned are mandatory before starting this drug.

Staying on Golimumab

Tips to Stay on Track:

Some patients see improvement in their symptoms within a few weeks, but it can take months for some. If any side effects are noticed, seek help immediately so the dosage can be altered or the drug can be stopped. Do not forget to report infection and allergy symptoms, if any. Also, follow the dosing and treatment schedule set by the physician.

Three points to remember,

• 1) Missing a dose will impact the treatment outcome, so stick to the schedule.

• 2) Set goals with the help of a doctor.

• 3) Follow up regularly with the doctor and let them know the progress.

For Doctors

Indication:

Golimumab is used in adults with unacceptable drug responses or those intolerant to other conventional treatments. Methotrexate is often used as an adjunct to the drug.

Pharmacology:

Mechanism of Action:

Golimumab is a human monoclonal antibody that attaches to the TNF-alpha. This results in the inhibition of the TNF-alpha from binding to the receptors and blocks its action. Increased levels of TNF-alpha in the blood, synovium, and joints are the primary pathogenesis by which conditions like rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis occur. It causes articular inflammation, which is pathognomonic for rheumatoid arthritis. Golimumab also altered the in vitro biological effects mediated by TNF, such as the expression of adhesion proteins for infiltration of leukocytes and secretion of the proinflammatory cytokines.

Pharmacodynamics:

Treatment with Golimumab in rheumatoid arthritis patients resulted in the following:

• Reduction in C-reactive proteins.

• Reduction in interleukin-6.

• Reduction in matrix metalloproteinase-3.

• Reduction in intercellular adhesion molecules.

• Reduction in vascular endothelial growth factor.

Chemical Taxonomy:

Ingredients:

The drug contains 50 milligrams of Golimumab antibody in 0.5 milliliters of solution. Every 0.5 ml solution contains 50 mg of Golimumab antibody, 0.44 mg of L-histidine and L-histidine monohydrochloride monohydrate, 20.5 mg of sorbitol, 0.08 mg of polysorbate 80, and water.

Absorption:

When the drug is administered through a subcutaneous route, the time to reach maximum serum concentrations (Tmax) ranges from two to six days and a mean serum concentration (Cmax) of 2.5 micrograms per milliliter. The absolute bioavailability of Golimumab was estimated to be approximately 53 percent. After administering 50 milligrams of the drug, the serum concentrations reached a steady state by week 12 and a mean steady-state serum concentration of 0.4 to 0.6 micrograms/milliliters. When the drug is combined with Methotrexate, patients with rheumatoid arthritis have 52 percent higher mean steady-state serum concentrations than those without Methotrexate.

Metabolism:

Similar to endogenous IgG (immunoglobulin G), Golimumab gets degraded into small peptides and amino acids through the catabolic pathways.

Elimination:

The half-life is two weeks for 50 mg of Golimumab. Monoclonal antibodies like Golimumab are not excreted through the renal or hepatic pathways.

Warnings and Precautions:

• Infections: Treatment with Golimumab should not be initiated in individuals with active infection. Patients above 65 years and under steroid therapy are at a higher risk for developing infections. The most common infections are tuberculosis, hepatitis B, and invasive fungal infections.

• Malignancy - Immunosuppressant treatment does increase the risk of certain types of cancer. Even though cancers have been reported in clinical studies, the exact role of Golimumab here is not fully understood.

• Hypersensitivity Reactions - 0.3 percent of patients in clinical trials had to stop treatment with Golimumab due to hypersensitivity reactions. The most common allergic reactions reported are rash at the injection site, skin rash, and urticaria.

• Liver Disease - As this drug is known to increase transaminase levels, it is not recommended for patients with active liver disease or hepatic impairment.

• Live Vaccines - Live vaccines should be avoided while the patient is on this drug due to an increased risk of infections. There is no data on the possible secondary transmission of infection from a vaccinated patient taking Golimumab to others.

Indications and Uses:

Rheumatoid Arthritis - For active cases of rheumatoid arthritis (RA) in adults who failed to respond to or tolerate more than one disease-modifying antirheumatic drug (DMARDs).

Dosage Strength and Forms:

Golimumab is injected subcutaneously. An injection of 50 mg/mL is used in a pre-filled syringe. The drug is clear to pale yellow.

Contraindications:

Avoid Golimumab in patients with known hypersensitivity to the drug or the inactive ingredients in the formulation.

Results from Clinical Trials:

The effectiveness and safety of Golimumab were evaluated in three multicenter, randomized, double-blind controlled trials in 1542 patients aged above 18 years with moderate to severe rheumatoid arthritis. This was determined according to the American College of Rheumatology (ACR) criteria for three months before administering the agent. The patients with at least four swollen and four tender joints were selected. Golimumab was administered to these patients at 50 mg every four weeks. The patient’s responses were observed, and the data was analyzed through week 24.

• In study group 1, 445 patients treated with a biologic TNF-alpha blocker were evaluated. In group 2, 444 patients with a stable dose of 15 mg/week of Methotrexate and who had not been treated with a TNF blocker were evaluated. In group 3, 637 patients not previously treated with Methotrexate and TNF blockers were evaluated.

• In groups 1 and 2, great improvement in the condition was observed compared to the control group.

Other Specifications:

• Golimumab in Pregnant Women: Not many studies have tested its efficacy in pregnant women. The ability to harm the fetus in pregnant women is also not known. One study in which Golimumab was subcutaneously given to a pregnant monkey showed no harm or developmental defects to the fetus. The drug should be prescribed during pregnancy only if necessary and under the doctor’s advise.

• Golimumab in Lactating Women: The excretion of the drug in breast milk is not known. In studies done in monkeys, it was found that Golimumab was present in human milk at concentrations that were 400-fold lower than the maternal serum concentrations.

• Golimumab in Pediatric Patients: The effectiveness and safety of the drug for those under 18 years of age have not been evaluated.

• Golimumab in Geriatric Patients: Patients older than 65 are more prone to infections. So special attention must be given to these patients while prescribing Golimumab as a medication.