What is Sarilumab used for?

Introduction to Sarilumab

Sarilumab, marketed under the trade name Kevzara, is a monoclonal antibody that targets the interleukin-6 receptor (IL-6R). Developed through a collaboration between Regeneron Pharmaceuticals and Sanofi, Sarilumab is primarily indicated for the treatment of moderate to severe rheumatoid arthritis (RA) in adults who have shown an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. The drug was approved by the U.S. Food and Drug Administration (FDA) in 2017 and has since garnered attention in the medical community for its efficacy and relatively well-tolerated profile. In addition to RA, Sarilumab has been investigated for treating other inflammatory conditions, including its potential use in managing severe COVID-19 cases where an overactive immune response, often referred to as a cytokine storm, plays a critical role. However, its primary and most studied application remains in the management of rheumatoid arthritis.

Sarilumab Mechanism of Action

Sarilumab functions by targeting the IL-6 receptor, a critical component of the immune system that plays a role in inflammation and autoimmunity. IL-6 is a cytokine—a type of small protein involved in cell signaling—that is produced by various cells, including T-cells and macrophages. It is instrumental in stimulating immune responses, acute phase reactions, and hematopoiesis (formation of blood cells). In the context of rheumatoid arthritis, IL-6 levels are often elevated, contributing to the chronic inflammation and joint damage characteristic of the disease.

By binding to the IL-6 receptor, Sarilumab inhibits the interaction between IL-6 and its receptor, thereby blocking the downstream signaling pathways that lead to inflammation. This inhibition results in decreased production of acute-phase proteins, reduction in inflammatory cell infiltration, and a decrease in the levels of other inflammatory cytokines. The overall effect is a reduction in the signs and symptoms of rheumatoid arthritis, such as pain, swelling, and stiffness, as well as a slowing of disease progression.

How to Use Sarilumab

Sarilumab is administered via subcutaneous injection, typically given once every two weeks. The recommended starting dose is usually 200 mg, but this may be adjusted based on the patient's response and tolerability. Some patients may start at a lower dose of 150 mg, especially if they are at a higher risk of developing side effects. The medication can be injected into the thigh, abdomen, or the upper arm, and patients are often trained to self-administer the injections. If self-administration is not an option, healthcare providers can perform the injections.

The onset of action for Sarilumab can vary among individuals. Some patients may begin to notice an improvement in their symptoms within a few weeks, while for others it may take several months to experience the full therapeutic benefits. It is important to continue the medication as prescribed, even if symptoms do not improve immediately, and to consult with a healthcare provider before making any changes to the treatment regimen.

What is Sarilumab Side Effects

Like all medications, Sarilumab can cause side effects, though not everyone will experience them. Common side effects include injection site reactions (such as redness, swelling, and pain), upper respiratory tract infections, urinary tract infections, and increases in liver enzymes. These side effects are generally mild to moderate in severity and often resolve on their own without the need for additional treatment.

However, there are also potential serious side effects that patients should be aware of. These include:

1. **Infections:** Because Sarilumab suppresses the immune system, there is an increased risk of serious infections, such as tuberculosis, bacterial sepsis, invasive fungal infections, and other opportunistic infections. Patients should be monitored for signs of infection and should undergo screening for latent tuberculosis before starting treatment.

2. **Gastrointestinal Perforations:** Although rare, gastrointestinal perforations, particularly in the stomach and intestines, have been reported. Patients with a history of diverticulitis or ulcers may be at a higher risk.

3. **Liver Enzyme Elevations:** Sarilumab can cause increases in liver enzymes, which may indicate liver damage. Regular monitoring of liver function tests is recommended during treatment.

4. **Hematologic Effects:** Changes in blood cell counts, including decreases in neutrophil counts and platelet counts, can occur. Blood tests should be conducted regularly to monitor for these changes.

Contraindications for Sarilumab include a known hypersensitivity to the drug or any of its components, as well as active, serious infections. Additionally, caution should be exercised in patients with a history of recurrent infections or other conditions that predispose them to infections.

What Other Drugs Will Affect Sarilumab

Several drugs can interact with Sarilumab, potentially affecting its efficacy or increasing the risk of adverse effects. These interactions can be pharmacodynamic (related to the drug's effects on the body) or pharmacokinetic (related to the drug's absorption, distribution, metabolism, and excretion). Some key interactions include:

1. **Biologic DMARDs:** The use of Sarilumab in combination with other biologic DMARDs, such as TNF inhibitors (e.g., etanercept, adalimumab), is generally not recommended due to an increased risk of serious infections and other adverse effects.

2. **Immunosuppressants:** Caution should be exercised when using Sarilumab alongside other immunosuppressive agents, such as corticosteroids or methotrexate. Although methotrexate is commonly used in combination with Sarilumab, close monitoring is required to mitigate the risk of infections and other side effects.

3. **CYP450 Substrates:** IL-6 is known to modulate the expression of certain cytochrome P450 (CYP450) enzymes. By inhibiting IL-6 signaling, Sarilumab can affect the metabolism of drugs that are CYP450 substrates, such as warfarin (an anticoagulant), certain statins (used to lower cholesterol), and some oral contraceptives. Dose adjustments of these medications may be necessary when starting or stopping Sarilumab.

4. **Live Vaccines:** Patients receiving Sarilumab should avoid live vaccines, as the medication can interfere with the body's ability to mount an adequate immune response, increasing the risk of infection from the vaccine itself.

In summary, Sarilumab is a promising treatment for rheumatoid arthritis, offering significant benefits in terms of symptom relief and disease progression. However, its use requires careful consideration of potential side effects, contraindications, and drug interactions. Patients should work closely with their healthcare providers to ensure that Sarilumab is used safely and effectively as part of their overall treatment plan.