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AAP issues guidance on managing infectious complications of biologic response modifiers

July 18, 2016

A new AAP clinical report provides comprehensive guidance on factors to consider prior to, during and following the use of biologic response modifiers (BRMs) that dampen the immune system and are used increasingly to treat conditions such as juvenile idiopathic arthritis, psoriatic arthritis or inflammatory bowel disease. They often are used in combination with other immunosuppressive agents, such as methotrexate and corticosteroids (see table).

The report titled Infectious Complications With the Use of Biologic Response Modifiers in Infants and Children from the AAP Committee on Infectious Diseases is available at and will be published in the August issue of Pediatrics.

While the risk varies with the class of BRM, patients receiving immune-dampening BRMs generally are at increased risk of infection or reactivation with mycobacterial infections (Mycobacterium tuberculosis and nontuberculous mycobacteria), some viral infections (herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, hepatitis B), fungal infections (histoplasmosis, coccidioidomycosis) and other opportunistic infections. As a result, pediatricians using BRMs need to determine the risk of the patient acquiring these infections based on the history (including exposure, residence, and travel and immunization history) and selected baseline screening test results.

Recommendations include providing routine immunizations at least two weeks (with inactivated or subunit vaccines) or four weeks (with live vaccines) prior to initiation of BRMs whenever feasible and giving inactivated influenza vaccine annually. While inactivated and subunit vaccines should be given when needed while on BRM, live vaccines should be avoided except under special circumstances and in consultation with an infectious diseases specialist.

If the patient develops a febrile or serious respiratory illness during BRM therapy, consideration should be given to stopping the BRM while searching for and treating possible infectious causes.

Dr. Davies is lead author of the clinical report and a member of the AAP Committee on Infectious Diseases.

FDA-approved biologic response modifiers and indications
Generic name (Year(s) FDA approved for indications) Trade name Mechanism of action Usual route,
FDA-approved indication#
(1999, 2009)
Remicade TNF-α inhibitor (anti-TNF-α chimeric monoclonal IgG1κ antibody) IV,
7.5–9.5 days
Crohn’s disease, [rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis]
Enbrel TNF-α inhibitor (soluble TNF-α receptor fusion protein) SQ,
70–132 h
Juvenile idiopathic arthritis,
[rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis]
Humira TNF-α inhibitor (Anti-TNF-α humanized monoclonal IgG1 antibody) SQ,
10–20 days
Juvenile idiopathic arthritis,
[rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease]
Simponi TNF-α inhibitor (Anti-TNF-α IgG1κ antibody) SQ,
7–20 days
[Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis]
Certolizumab pegol
Cimzia TNF-α inhibitor (PEGylated human Fab antigen binding)  SQ,
14 days
[Rheumatoid arthritis, Crohn's disease]
(2005, 2009)
Orencia Anti-CTLA4 selective T cell costimulation modulator protein; (blocks TNF-α, IL-2 and interferon–γ production) IV or SQ,
8–25 days
Juvenile idiopathic arthritis,
[rheumatoid arthritis]
Kineret Recombinant Anti-IL1 receptor antagonist SQ,
4–6 h
[Rheumatoid arthritis]
Rituxan Anti-CD20 therapy IV,
14–62 days
[Rheumatoid arthritis, non-Hodgkin lymphoma]
Actemra Anti-IL6 humanized monoclonal antibody IV,
8–14 days
[Rheumatoid arthritis]
Stelara Anti-IL12 and IL23 humanized monoclonal antibody SQ,
20–24 days
[Psoriatic arthritis, plaque psoriasis]
(2009, 2013)
Ilaris Anti-IL1B human monoclonal antibody SQ,
26 days
Juvenile idiopathic arthritis
(2008, 2013)
Tysabri Humanized anti integrin alpha 4 subunit monoclonal antibody (reduces leukocyte adhesion and transmigration) IV,
11 days
[Crohn's disease
multiple sclerosis]
Benlysta Human IgG1λ monoclonal antibody against soluble human B lymphocyte stimulator protein IV,
19 days
[Systemic lupus erythematosus]
(2008, Orphan Drug)
Arcalyst IL1 receptor fusion protein SQ,
8.6 days
Xeljanz Small molecule protein kinase inhibitor of JAK-3 and JAK 1 Oral,
3 h
[Rheumatoid arthritis]

IV, intravenous; SQ, subcutaneous; CAPS, cryopyrin-associated periodic syndromes (consisting of familial cold autoinflammatory syndrome and Muckle-Wells syndrome)

#FDA approved indication: for underlined conditions, safety and efficacy have been established in children <18 years; for bracketed indications, safety and efficacy have been shown only in adults. Infliximab, etanercept and adalimumab have been used off-label for scleritis, but none are FDA approved for this condition.



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