Biologic agents have been used for more than 20 years in pediatric medicine—initially to treat inflammatory bowel disease and more recently in dermatology and rheumatology—and have transformed management of many diseases.

Biologic agents are typically thought of in terms of parenterally administered monoclonal antibodies, but discussion of such therapies should also include Janus kinase (JAK) inhibitors, which are small protein molecules that can be given orally. 

All of these agents allow important inflammatory disease pathways to be targeted,

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inhibiting target cells and specific cytokines involved in the disease process.  While effective for numerous diseases, biologic agents can be associated with potentially serious side effects, explaining their use in more moderate-to-severe disease activity. While their specific mechanisms of action may differ, biologic agents have similar side effect profiles and warnings/precautions as do JAK inhibitors. The list below characterizes biologic agents and JAK inhibitors. Clinicians should be intimately familiar with prescribing information for each agent and inhibitor. 

Biologic agents (parenteral) recently approved by FDA for pediatric use

Belimumab is a B-lymphocyte stimulator-specific inhibitor indicated for treatment of patients 5 years and older with active, autoantibody-positive systemic lupus erythematosus who are receiving standard therapy. The recommended dose is 10 mg/kg IV every 2 weeks for the first three doses and every 4 weeks thereafter. Belimumab may be associated with nausea, diarrhea, nasopharyngitis, insomnia, and injection site reactions; prophylactic premedication for infusion reactions and hypersensitivity reactions should be considered. (Belimumab is one of the only FDA-approved drugs for lupus.)

Canakinumab is an IL-1β blocker indicated for treatment of systemic juvenile idiopathic arthritis (JIA) in patients 2 years and older. The recommended dose is 4 mg/kg (maximum of 300 mg) in patients with body weight ≥ 7.5 mg administered subcutaneously (SC) every 4 weeks. Canakinumab may be associated with infections, abdominal pain, and injection-site reactions. 

Dupilumab is an IL-4 receptor alpha antagonist indicated for treatment of moderate-to-severe atopic dermatitis in patients 6 years and older whose disease is not adequately controlled with topical therapies, or for when such therapies are not advisable. Dupilumab can be used with or without topical corticosteroids. The recommended loading dose in pediatric patients (6–17 years of age) is based on body weight (600 mg SC for 15 - < 30 kg; 400 mg SC for 30 - < 60 kg; and 600 mg SC for > 60 kg); subsequent doses are 300 mg SC every 4 weeks, 200 mg SC every 2 weeks, and 300 mg SC every 2 weeks, respectively, for body weight. Adverse reactions include injection site reactions, oropharyngeal pain, and eosinophilia; hypersensitivity reactions also have occurred.

Ixekizumab is a humanized IL-17A antagonist indicated for treatment of patients 6 years and older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The recommended dose for pediatric use is based on body weight: for < 25 kg, the initial dose is 40 mg SC followed by 80 mg SC every 4 weeks; for 25–50 kg, the initial dose is 80 mg SC followed by 40 mg SC every 4 weeks; for >50 kg, the initial dose is 160 mg SC, followed by 80 mg SC every 4 weeks. Ixekizumab may be associated with injection site reactions, upper respiratory tract infections, nausea, and tinea infections.

Secukinumab is a human IL-17A antagonist indicated for treatment of moderate-to-severe plaque psoriasis in patients 6 years and older who are candidates for systemic therapy or phototherapy, active psoriatic arthritis in patients 2 years and older, and active enthesitis-related arthritis in patients 4 years and older. The recommended pediatric dose differs between indications—please refer to prescribing information for exact dosing. Secukinumab may be associated with nasopharyngitis, diarrhea, andupper respiratory tract infections.

Ustekinumab is a human IL-12/23 antagonist indicated for treatment of moderate-to-severe plaque psoriasis in patients 6 years and older who are candidates for systemic therapy or phototherapy. The recommended dose for pediatric use is based on body weight at the initial dose, 4 weeks later, and every 12 weeks subsequently: < 60 kg is SC 0.75 mg/kg; 60-100 kg is 45 mg SC; > 100 kg is 90 mg SC. Ustekinumab may be associated with nasopharyngitis, upper respiratory tract infections, headaches, and fatigue; anaphylaxis or significant hypersensitivity reactions also may occur.   

Available biologic agents for pediatric use in dermatology and rheumatology also include abatacept, adalimumab, etanercept, and tocilizumab. 

Oral JAK inhibitors recently approved by FDA for pediatric use

Tofacitinib oral solution is a JAK inhibitor indicated for treatment of active polyarticular course JIA in patients 2 years and older who have had an inadequate response or intolerance to one or more TNF blockers. The recommended dose is 5 mg (or weight-based equivalent) twice a day orally. Tofacitinib may be associated with upper respiratory tract infections, nasopharyngitis, diarrhea, and headaches; combination with biologic DMARDs or potent immunosuppressants is not recommended. 

Upadacitinib is indicated for treatment of refractory, moderate-to-severe atopic dermatitis in patients 12 years of age and older whose disease is not adequately controlled with other systemic drug products (including biologics), or when use of those therapies is inadvisable. The recommended dose (in patients weighing at least 40 kg) is 15 mg once a day orally, increasing to 30 mg if response is inadequate. Upadacitinib may be associated with upper respiratory tract infections, acne, headache, nausea, abdominal pain, herpes zoster, myalgia, fatigue, and influenza-like illness; combination with other JAK inhibitors, biologic immunomodulators, or immunosuppressants is not recommended.

Limitations of biologic agents and JAK inhibitors

Adalimumab and etanercept have black-box warnings for serious infections and malignancies; tocilizumab has a black-box warning for risk of serious infections. Tofacitinib and upadacitinib have black-box warnings for serious infections, mortality, malignancy, major adverse cardiovascular events,  and thrombosis.

What this means for you

Although administered parenterally, biologic agents are convenient to use,

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have greater and more rapid effects,

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require less monitoring than traditional systemic agents, and have fewer drug interactions, thus providing a beneficial treatment option.