Actemra

Approved Uses

Actemra is primarily used to manage symptoms and slow the progression of several autoimmune and inflammatory disorders. It is commonly prescribed for the following conditions:

• Rheumatoid Arthritis: For adults with moderate to severe active rheumatoid arthritis who have not had an adequate response to other disease-modifying antirheumatic drugs (DMARDs).
• Giant Cell Arteritis: To treat inflammation of the lining of the arteries in adults.
• Polyarticular Juvenile Idiopathic Arthritis (PJIA): For children aged 2 years and older with active PJIA.
• Systemic Juvenile Idiopathic Arthritis (SJIA): For children aged 2 years and older with active SJIA.
• Systemic Sclerosis-Associated Interstitial Lung Disease: To slow the rate of decline in lung function in adults with this specific lung condition.

Acute Medical Situations

Actemra is also used in specific hospital or clinical settings for acute conditions:

• Cytokine Release Syndrome (CRS): For adults and children aged 2 years and older who experience severe or life-threatening CRS following CAR T-cell therapy.
• COVID-19: For hospitalized adults who are receiving systemic corticosteroids and require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Depending on the condition being treated, Actemra may be used alone or in combination with other medications, such as methotrexate or other non-biologic DMARDs.

Mechanism of Action

Actemra belongs to a class of medications known as interleukin-6 (IL-6) receptor antagonists. In a healthy body, IL-6 is a protein that helps regulate the immune system and the inflammatory response. However, in people with certain autoimmune diseases, the body produces too much of this protein.

When there is an excess of IL-6, it attaches to receptors on the surface of cells, sending signals that cause inflammation, pain, and swelling. Actemra works by:

• Binding to receptors: The medication attaches itself to both soluble and membrane-bound IL-6 receptors.
• Blocking signals: By occupying these receptors, Actemra prevents the IL-6 protein from connecting with the cells.
• Reducing inflammation: Because the inflammatory signal is blocked, the body's immune response is dampened, which helps to decrease joint damage and other symptoms.

By interfering with this specific part of the immune system, the medication helps manage the underlying cause of inflammation rather than just treating the pain.

Common Side Effects

Many people using Actemra experience mild side effects. These often include:

• Upper respiratory tract infections, such as the common cold or sinus infections
• Headache
• High blood pressure
• Injection site reactions, including redness, itching, or pain
• Nausea or stomach pain
• Mouth sores

Serious Side Effects

While less common, some side effects can be severe and require immediate medical attention. These include:

• Serious Infections: Actemra can lower the immune system's ability to fight infections, including tuberculosis and other bacterial, fungal, or viral infections.
• Gastrointestinal Tears: Some patients have experienced tears (perforations) in the stomach or intestines, often as a complication of diverticulitis.
• Liver Problems: Signs may include yellowing of the skin or eyes (jaundice), dark urine, or extreme fatigue.
• Changes in Blood Counts: The medication may cause a decrease in white blood cells or platelets, which can increase the risk of infection or bleeding.
• Allergic Reactions: Severe reactions, including hives, swelling of the face or throat, and difficulty breathing, can occur during or after treatment.
• Nervous System Issues: In rare cases, new or worsening symptoms of nervous system disorders, such as multiple sclerosis, have been reported.
• High Cholesterol: Increases in blood cholesterol levels are common and may require monitoring by a healthcare provider.

Serious Infections

Actemra carries a boxed warning regarding the risk of serious infections that may lead to hospitalization or death. These include tuberculosis (TB), bacterial, invasive fungal, viral, or other opportunistic infections. Patients should be screened for latent TB before starting treatment and monitored for signs of infection throughout therapy. If a serious infection develops, treatment is typically interrupted until the infection is controlled.

Gastrointestinal Perforation

There is an increased risk of developing a hole in the stomach or intestines, known as gastrointestinal perforation. This risk is notably higher in patients with a history of diverticulitis. The concurrent use of other medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, may further increase this risk.

Laboratory Monitoring

Regular blood tests are necessary to monitor for potential side effects, as Actemra can cause changes in several laboratory values:

• Liver Function: Elevations in liver enzymes may occur, which can indicate liver injury.
• Blood Counts: Decreases in white blood cell counts (neutropenia) and platelet counts (thrombocytopenia) have been observed, which may affect the body's ability to fight infection or clot blood.
• Lipids: Increases in cholesterol and triglyceride levels may occur during treatment.

Hypersensitivity and Allergic Reactions

Serious allergic reactions, including anaphylaxis, have been reported during or after administration. These reactions can occur even if the patient has tolerated previous doses. If a serious hypersensitivity reaction occurs, the medication must be permanently discontinued.

Other Warnings and Precautions

• Vaccinations: Live vaccines should not be administered during treatment, as the medication may interfere with the body's immune response to the vaccine.
• Neurological Disorders: Rare instances of central nervous system demyelinating disorders, such as multiple sclerosis or chronic inflammatory demyelinating polyneuropathy, have been reported.
• Malignancy: The impact of treatment on the development of malignancies is not fully known, but medications that suppress the immune system may increase the risk of certain cancers.

Pregnancy

There is limited information regarding the safety of Actemra use during pregnancy. It is currently unknown if the medication will cause harm to an unborn baby. Healthcare providers generally recommend that Actemra be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

If you are pregnant or planning to become pregnant, you should discuss your treatment options with your doctor. There is a pregnancy exposure registry that monitors the health of individuals who use Actemra while pregnant and the health outcomes of their infants.

Breastfeeding

It is not known whether Actemra passes into human breast milk or if it could affect a nursing child. Because many medications can be excreted in breast milk and may cause serious side effects in an infant, a decision must be made whether to discontinue breastfeeding or discontinue the drug. This decision should be made in consultation with a healthcare provider, considering the importance of the medication to the mother's health.

Available Forms

Actemra is provided in two primary administration formats depending on the condition being treated and the patient's needs:

• Intravenous (IV) Infusion: This form is a concentrated solution supplied in single-dose vials. It is administered by a healthcare professional into a vein, typically in a clinical setting.
• Subcutaneous (SC) Injection: This form is injected into the fatty tissue just under the skin. It is available in two delivery methods:
  • A single-dose prefilled syringe.
  • A single-dose prefilled autoinjector.

The subcutaneous injection may be administered at home by a patient or caregiver after receiving proper training from a healthcare provider. The intravenous form must be administered by a medical professional.

Strengths

Actemra is supplied in single-use containers. The specific dose and frequency of administration are determined by a healthcare provider based on the patient's body weight and the specific condition being treated.

FDA Approval History

Actemra (tocilizumab) was first approved by the U.S. Food and Drug Administration (FDA) in January 2010. It belongs to a class of drugs known as interleukin-6 (IL-6) receptor antagonists. In September 2023, the FDA approved the first biosimilar version of Actemra for the treatment of adult and pediatric arthritis.

Approved Indications

The FDA has approved Actemra for the treatment of several conditions, including:

• Rheumatoid arthritis in adults
• Giant cell arteritis
• Systemic sclerosis-associated interstitial lung disease
• Polyarticular juvenile idiopathic arthritis
• Systemic juvenile idiopathic arthritis
• Cytokine release syndrome caused by CAR T-cell therapy
• Hospitalized adults with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation

Boxed Warning

Serious Infections: Actemra contains a boxed warning because it can lower the immune system's ability to fight infections. Some people have developed serious infections while taking this medication, including tuberculosis (TB) and infections caused by bacteria, fungi, or viruses that can spread throughout the body. These infections may lead to hospitalization or death.

Safety Monitoring

The FDA monitors the safety of Actemra through the FDA Adverse Event Reporting System (FAERS). In 2018, the FDA identified a potential signal of serious risk regarding hepatotoxicity (liver injury), which resulted in updates to the drug's safety information and ongoing monitoring of liver health in patients using the medication.

Factors Affecting Cost

As a biologic medication, Actemra is typically more expensive than non-biologic drugs. The total cost is influenced by several factors:

• Administration Method: Actemra is available as an intravenous (IV) infusion or a subcutaneous injection. Infusions administered in a clinical setting may involve additional costs for the facility and healthcare provider services.
• Dosage and Frequency: The amount of medication prescribed is often based on the patient's weight and the specific condition being treated, which directly impacts the price per dose.
• Insurance and Pharmacy Benefits: Coverage varies widely between private insurance plans, Medicare, and Medicaid. Many plans require prior authorization or may place the drug on a specialty tier with higher copayments.

Biosimilar Availability

The FDA has approved biosimilar versions of Actemra. Biosimilars are medications that are highly similar to the original biologic in terms of safety and effectiveness but are often available at a lower cost. The availability of these alternatives may provide more affordable options for patients and healthcare systems.

Financial Assistance Programs

Because of the high cost of biologic therapy, financial assistance may be available. This can include manufacturer-sponsored copay cards for patients with commercial insurance or patient assistance programs for those who are uninsured or underinsured. Eligibility for these programs is typically based on income and insurance status.