Biologic Therapy In Pediatrics: An Overview

Introduction:

Biological therapy is slowly being approved for pediatric use with the changing time. In the future, rheumatologists and dermatologists can access the pathways per the patient's need. The evolution of these therapies is never-ending. In the future, biological treatment may be customized to the patient’s cytokine and genetic profile and the type and severity of the disease. Nowadays, a need exists to specify which patients should be considered for a specific biological treatment. These drugs probable side effects and new applications represent a challenge for pediatric dermatologists and rheumatologists.

Why Are Biological Agents Important?

1. Biologic agents allow us to target important inflammatory pathways.

2. Specific cytokines are targeted that are involved in the disease process by biologic agents.

3. Biologic agents help to inhibit the growth of target diseased cells.

How Are These Agents Administered in the Body?

• Biologic agents are administered in the form of parenterally administered monoclonal antibodies, a specific protein made in the laboratory binds to a specific target, like an antigen or a cancer cell.

• Given in the form of injection or given orally.

What Are the Different Biological Agents Used in the Therapy?

Biological agents administered through injection technique are the following:

1. Belimumab : It is a B-lymphocyte stimulator-specific inhibitor. Used in treating systemic lupus erythematosus. Patients receiving the treatment should be at least five years or older. Belimumab is an approved drug by the FDA (Food and Drug Administration) for lupus. Dosage - 10 mg/kg (milligrams per kilogram) IV (Intravenous) every two weeks for the initial three doses and then every four weeks.

2. Canakinumab: It is an IL-1beta (a form of interleukin 1) blocker. Used in treating systemic juvenile idiopathic arthritis. Patients age should be at least two years or older. Dosage - 4 mg/kg (milligrams per kilograms) every four weeks.

3. Dupilumab: It is an IL-4 (interleukin 4)receptor alpha antagonist. Used in treating moderate to severe atopic dermatitis Patients age should be at least six years or older. Dosage -For six to 17 years old children- it is based on body weight. For 15 kg (kilogram) - less than 30 kilograms: 600 milligrams subcutaneous. For 30 kilograms - less than 60 kg: 400 milligrams subcutaneous (SC). For more than 60 kilograms: 600 milligrams subcutaneous (SC). The next doses should be 300 milligrams SC, 200 milligrams subcutaneously every two weeks, and 300 milligrams subcutaneously (SC) every two weeks for the particular body weight.

4. Ixekizumab: It is a humanized IL-17A (interleukin 17) antagonist. Used in treating moderate and severe psoriasis. Patients age should be at least six years or older. Dosage is as follows: If the weight is less than 25 kg - the first dose is 40 mg subcutaneously. The second dose is- 80 mg SC, followed every weekend. If the weight is 25 kg to 50 kg -- the first dose is 80 mg SC, followed by the second dose, 40 mg SC, every four weeks. If weight is more than 50 – the first dose is 160 mg SC and the second dose is 80 mg, followed every four weeks.

5. Secukinumab: It is an IL-17A antagonist. Used to treat moderate and severe plaque psoriasis. Patients' age should be at least six years or older. Also used in patients with active enthesitis arthritis two years and older. And also used in patients undergoing phototherapy.

6. Ustekinumab: It is a human IL-12/23 antagonist. Used to treat moderate and severe plaque psoriasis. Patients' age should be at least six years and older. Dosage- It is based on body weight at the initial dose, four weeks later, and every 12 weeks later. If the weight is more than 60 kilograms the dose is SC 0.75 milligrams per kilograms. If the weight is 60 to 100 kilograms, the dosage is 45 milligrams SC. If the weight is 100 kilograms, the dosage is 90 milligrams SC.

Are There Any Side Effects Associated With These Biological Agents?

Yes, a few side effects are seen as listed below:

With Belimumab: Nausea, diarrhea (watery stools), insomnia (lack of sleep), nasopharyngitis (viral infection of nose and throat), hypersensitivity reactions (skin rash).

Canakinumab: Abdominal pain, infections. reactions on injection site.

Dupilumab: Eosinophilia (a high level of disease-fighting white blood cells), Oropharyngeal pain ( pain in pharynx behind throat),reactions on injection site, hypersensitivity reactions.

Ixekizumab: Reactions on injection site, upper respiratory tract infections. nausea, tinea infection (fungal infection of the skin).

Secukinumab: Diarrhea, upper respiratory tract infections, nasopharyngitis (inflammatory attack of the pharynx and nasal cavity).

Ustekinumab: Fatigue, headaches, hypersensitivity, nasopharyngitis, upper respiratory tract infections.

Are Any Other Biological Agents Available?

The following agents are available:

1. Abatacept.
2. Adalimumab.
3. Etanercept.
4. Tocilizumab.

Biological Agents Administered Orally Are :

• Tofacitinib: It is an oral solution. It is a JAK inhibitor. Used in the treatment of active polyarticular courses in juvenile idiopathic arthritis. The patient's age should be two years or older. Dosage - 5 mg (milligrams), or according to the weight, is given twice daily.

• Upadacitinib: Used in the treatment of refractory moderate and severe atopic dermatitis. Given in cases where systemic drugs fail. The patient's age should be 12 years and older. Dosage - If the patient's weight is 40 kg to 15mg (once a day orally), increase to 30 mg if the response is not expected.

What Are the Side Effects Associated With Oral Biological Agents?

• Tofacitinib: Upper respiratory tract infections, diarrhea, headache, nasopharyngitis.

• Upadacitinib: Fatigue, headache, upper respiratory tract infections, herpes zoster(a painful rash caused by infection of a virus causing chickenpox), nausea, influenza, abdominal pain, myalgia (fever with pain).

Are Biological Agents and Therapy Effective?

They will remain the effective treatment choice for dermatological and rheumatological diseases until any new technology is developed.

What Cautions Should Be Followed With the Use of Biological Agents?

Very limited pediatric data is available as compared to adults. Some biological agents can cause serious diseases like:

1. Adalimumab and etanercept have warnings issued for serious infections and malignancies.

2. Tocilizumab has a warning against risk for serious infections.

3. Tofacitinib and upadacitinib have warnings against serious infections, malignancy (cancer), major adverse cardiovascular events, thrombosis (blood clot), and mortality ( death rate).

Conclusion:

It has been 20 years since we started using biological agents in pediatric use, and it is still evolving. Patients with severe diseases can be treated by using personalized therapy. Biological agents are designed in such a way that they can reduce the signs and symptoms of rheumatoid arthritis and psoriasis and can also slow down the diseases. Biological therapy demonstrates significant benefits in terms of outcomes for the patients. Even if biological agents are administered parenterally, they are easy to use, have greater immediate effects, require less monitoring than conventional systemic agents, and have rarer drug interactions, thus delivering a beneficial treatment opportunity.