Spesolimab-sbzo - Dosage, Uses, and Side Effects

Overview

Spesolimab-sbzo is a drug indicated to treat adult patients with generalized pustular psoriasis (GPP) flares (a rare and severe skin disorder). It belongs to a group of medications called interleukin (IL) receptor antagonists or interleukin inhibitors and is used for immune-mediated disorders. It was initially designed as an orphan drug and later approved by the United States Food and Drug Administration (US FDA) on 1st September 2022. It is the first therapy that specifically targets the IL-36 pathway and has been evaluated for treating GPP flares after controlled clinical trials. The drug is also under investigation for preventing generalized pustular psoriasis flares and for the management of other skin diseases.

How Does Spesolimab-sbzo Work?

Spesolimab-sbzo is a biological drug (a drug made of living cells) or a monoclonal antibody (man-made proteins) that acts by blocking a natural protein in the body called interleukin-36 (IL36R) responsible for producing abnormal inflammatory responses. Spesolimab-sbzo inhibits this pathway, which is overexpressed in generalized pustular psoriasis. The binding of Spesolimab-sbzo to interleukin-36 prevents the activation of IL36R ligands, thus reducing the symptoms of GPP flare. It usually works within a week of treatment, but if symptoms are observed even after a week, a second dose may be recommended.

Indications of Spesolimab-sbzo:

Spesolimab-sbzo is indicated for treating adult patients with generalized pustular psoriasis flares.

Contraindications of Spesolimab-sbzo:

• Spesolimab-sbzo is contraindicated in patients with a history of severe hypersensitivity (severe allergic reactions) to the drug or its components.

• Spesolimab-sbzo is not recommended for pregnant women and nursing mothers. It is also not preferred for children and elderly people.

Available Doses and Dose Forms:

Spesolimab-sbzo is a sterile, clear to slightly opalescent, preservative-free solution for intravenous administration. It is recommended as a single 900 mg (milligrams) dose for intravenous infusion over 90 minutes. In persistent generalized pustular psoriasis flares, an additional 900 mg dose can be administered after one week from the first dose. Spesolimab-sbzo must be inspected for any discoloration or diluted particulate matter before administration. If the solution appears cloudy, discolored, or contains particulates, it must be safely discarded.

Warnings and Precautions:

• Immediate hypersensitivity reactions, including anaphylaxis (severe allergic reactions) or delayed reactions, may occur in some patients following the Spesolimab-sbzo infusion. The treatment must be discontinued if the patients develop severe reactions, and appropriate treatment must be initiated. In the case of mild or moderate infusion-related reactions, the infusion must be stopped immediately, and appropriate treatment with antihistamines or corticosteroids must be considered. After the resolution of allergic reactions, the infusion can be started again, but at a slower rate with a gradual increase to complete the treatment.

• Spesolimab-sbzo can increase the risk of infections. In patients with a history of recurrent or chronic infections, the potential risks and benefits of Spesolimab-sbzo must be considered before starting the treatment. Patients must be instructed to seek immediate medical assistance if any signs and symptoms of infection are observed.

• Patients must be evaluated for tuberculosis (TB) infection (bacterial infection affecting the lungs) before starting treatment with Spesolimab-sbzo, as the drug cannot be administered to patients with active TB infection. Antitubercular therapy must be started before Spesolimab-sbzo in patients with latent TB (TB bacteria present in the body but without causing illness) or a history of TB. Patients must be monitored frequently for any signs and symptoms of TB during and after treatment with Spesolimab-sbzo.

• Live vaccines must be avoided during treatment with Spesolimab-sbzo. However, clinical studies have yet to be conducted on patients who have recently received live vaccinations.

Adverse Effects of Spesolimab-sbzo:

Adverse effects of Spesolimab-sbzo include:

• Nausea and vomiting.

• Fatigue (tiredness).

• Infusion site hematoma (abnormal collection of blood).

• Bruising (localized bleeding).

• Headache.

• Asthenia (weakness).

• Pruritus (itching).

• Bacteremia (presence of bacteria in the blood).

• Cellulitis (common bacterial infection of the skin).

• Urticaria (itchy rashes).

• Dyspnea (difficulty breathing).

• Upper respiratory tract infection.

• Urinary tract infection.

• Eye edema (swelling around the eyes).

For Patients

What Is Generalized Pustular Psoriasis?

Generalized pustular psoriasis (GPP) is a rare, long-term, severe form of skin disease characterized by the sudden occurrence of sterile pustules (small, painful pus-filled blisters) along with inflammation (swelling). The severity and frequency of the flares of GPP vary between patients and can last between two and five weeks; some patients may even require hospitalization.

The exact cause of this condition is unknown; however, it is known to be associated with a combination of genetic mutations and other risk factors such as infections, certain medications, stress, pregnancy, or menstruation. Some patients with GPP may have sudden flares that last for a few weeks, after which there is spontaneous remission, during which the skin completely or partially clears up.

Some of the signs and symptoms of generalized pustular psoriasis include:

• Red and inflamed skin.

• Pus-filled bumps.

• Fever.

• Tiredness.

• Swelling.

• Itching.

• Headache.

• Nausea.

• Joint pain.

• Muscle weakness.

The treatment of generalized pustular psoriasis includes topical and oral medications, phototherapy, and biological treatments.

What Is Spesolimab-sbzo?

Spesolimab-sbzo is a prescription medicine used to treat generalized pustular psoriasis (a severe form of psoriasis) in adult patients. The dose and treatment schedule are based on the severity of the condition. However, Spesolimab-sbzo may reduce the ability to fight infections; hence, the patient may be prone to frequent infections. The doctor must be consulted, and immediate medical assistance must be taken if the patient experiences any signs of infection, such as fever, chills, swelling, sore throat, and cough.

How Effective Is Spesolimab-sbzo?

Spesolimab-sbzo belongs to a group of medicines called monoclonal antibodies and works by blocking a protein in the body called interleukin-36 that is responsible for causing inflammation and other symptoms of generalized pustular psoriasis. This medication has received positive opinions in many countries worldwide and is also being developed for other conditions. It is usually a well-tolerated and highly effective medication. Though the drug is associated with mild to moderate side effects, no clinically relevant severe hypersensitivity reactions, safety concerns, or opportunistic infections (infections that often occur in people with weak immune systems) were evident during the clinical trials.

How Should Spesolimab-sbzo Be Taken?

Spesolimab-sbzo is administered by a healthcare provider intravenously (into the vein) by infusion over 90 minutes. It is usually a single 900-milligram dose. Still, if the flares persist even after the treatment, the doctor may recommend an additional dose of Spesolimab-sbzo after one week. The patient and caregivers can read the drug information leaflet or discuss it with the doctor to address any concerns or to understand the treatment.

What Are the Side Effects of Spesolimab-sbzo?

Some of the side effects of Spesolimab-sbzo include:

• Nausea and vomiting.

• Tiredness.

• Headache.

• Itching or itchy bumps.

• Cough.

• Chills.

• Muscle ache.

• Collection of blood under the skin at the infusion site.

• Respiratory infection.

• Urinary tract infection.

What Must the Patient Inform the Doctor Before Taking Spesolimab-sbzo?

• Patients must inform the doctor if they have a long-term infection or frequent infections before starting treatment with Spesolimab-sbzo.

• Patients must tell the doctor if they have tuberculosis or have been in close contact with someone who has TB (tuberculosis).

• Patients must inform the doctor if they have recently received or scheduled a vaccination.

• Before taking Spesolimab-sbzo, female patients must tell the doctor if they are pregnant, breastfeeding, planning, or suspecting pregnancy.

• Patients must tell the doctor if they are allergic to Spesolimab-sbzo, its components, or any other medications before starting the treatment.

• Before taking Spesolimab-sbzo, patients must inform their healthcare provider if they take herbal medicines, vitamins, nutritional supplements, other medications, or over-the-counter (OTC) drugs.

What Are the Precautionary Measures to Be Followed While Taking Spesolimab-sbzo?

• Spesolimab-sbzo may lower the ability of the immune system to fight infections, thus increasing the risk of frequent infections. Therefore, patients must inform the doctor if they have a history of chronic infections or are suffering from other medical conditions before starting the treatment.

• During the treatment with Spesolimab-sbzo, if the patients show any signs or symptoms of infection, such as fever, chills, cough, sore throat, muscle ache, or burning sensation during urinating, the doctor must be consulted immediately.

• The doctor will recommend a test for tuberculosis and may treat the patient in case of a history of TB or active tuberculosis before starting treatment with Spesolimab-sbzo.

• Live vaccinations must not be taken after the treatment with Spesolimab-sbzo.

• Hypersensitivity (severe allergic reactions) or infusion site reactions such as itching, dizziness, trouble breathing, swelling of the face, fever, and skin rash can occur in some patients during the treatment with Spesolimab-sbzo; in such situations, the doctor must be immediately consulted.

Dietary Considerations:

No dietary restrictions are required during the treatment with Spesolimab-sbzo unless instructed by the prescribing doctor.

Storage:

Spesolimab-sbzo must be refrigerated at 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit) in their original container to protect them from excess light. It must not be frozen. Before use, unopened vials may be stored at room temperature at around 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) in their original packaging to protect them from light.

For Doctors

Pharmacological Aspects of Spesolimab-sbzo:

Mechanism of Action:

Spesolimab-sbzo is a humanized monoclonal antibody (immunoglobulin G1) that acts by inhibiting interleukin-36 (IL-36) by signaling and specifically binding to the ligand IL36R. This prevents subsequent activation of IL36R by cognate ligands and causes downstream activation of profibrotic and proinflammatory pathways. However, the exact mechanism responsible for the association between reduced interleukin-36 activity and the treatment of GPP flares is not known.

Pharmacodynamics:

The pharmacodynamics of Spesolimab-sbzo for treating generalized pustular psoriasis have yet to be completely understood. However, inhibiting the signaling effects of interleukin-36 leads to the normalization of the C-reactive protein and suppression of the molecular pathways associated with GPP, thus reducing inflammation.

Pharmacokinetics:

• Absorption: Following the administration of a single dose of 900 mgSpesolimab-sbzo, the area under the curve (AUC) was 4750 mcg/day/ml (microgram per day per milliliter), and the maximum plasma concentration (Cmax) was 238 mcg/ml (microgram per milliliter). The area under the curve was dose proportionate and increased from 0.3 to 20 mg/kg (milligrams per kilogram). The terminal half-life of Spesolimab-sbzo was independent of the dose.

• Distribution: According to the pharmacokinetic analysis, the total volume of distribution at the steady state was 6.4 L (liter).

• Metabolism: The metabolic pathway of Spesolimab-sbzo is not determined; however, as a monoclonal antibody, it is estimated to be degraded via catabolic pathways into small peptides and amino acids similar to endogenous IgG.

• Excretion: The clearance rate of Spesolimab-sbzo based on the population pharmacokinetic model was around 0.184 L/day (liters per day), and the terminal half-life was 25.5 days.

Drug Interactions:

Drug interaction studies have not been conducted with Spesolimab-sbzo.

Clinical Studies:

A randomized, placebo-controlled, double-blind study was conducted to determine the safety and efficacy of the intravenous 900 mg of Spesolimab-sbzo in adult patients with generalized pustular psoriasis flares. The patients were instructed to discontinue any systemic or topical treatment for GPP if they were undergoing it before administering Spesolimab-sbzo. The mean age of the subjects was 43 years, and around 25 percent were previously treated with biological therapy. Spesolimab-sbzo was safe and effective with a consistent profile, regardless of the patient’s demographics or clinical characteristics.

Nonclinical Toxicology:

Carcinogenicity and mutagenicity studies have not been performed with Spesolimab-sbzo. No adverse effects were seen in male or female mice administered with Spesolimab-sbzo at intravenous doses up to 50 mg/kg (milligram per kilogram) twice a week.

Specific Considerations:

• Pregnancy: Limited data is available on the use of Spesolimab-sbzo, which is insufficient to determine the associated risks or adverse effects of the drugs in pregnant women.

• Lactation: Spesolimab-sbzo is a monoclonal antibody and is expected to be present in breast milk. However, no data is available to determine the presence of the drug in human milk, its effects on the breastfed infant, or milk production. The benefits of breastfeeding and the adverse effects of Spesolimab-sbzo on the infant must be considered, along with the mother’s requirement for the drug.

• Pediatric Use: The safety and effectiveness of Spesolimab-sbzo have not been established in children.

• Geriatric Use: A sufficient number of subjects above 65 years of age were not included in the clinical studies of Spesolimab-sbzo to determine their response compared to the younger subjects.