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 http://dx.doi.org/10.1542/peds.2016-1209 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, half-life |
FDA-approved indication# |
| Infliximab (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] |
| Etanercept (1998) |
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] |
| Adalimumab (2002) |
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] |
| Golimumab (2009) |
Simponi | TNF-α inhibitor (Anti-TNF-α IgG1κ antibody) | SQ, 7–20 days |
[Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis] |
| Certolizumab pegol (2009) |
Cimzia | TNF-α inhibitor (PEGylated human Fab antigen binding) | SQ, 14 days |
[Rheumatoid arthritis, Crohn's disease] |
| Abatacept (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] |
| Anakinra (2001) |
Kineret | Recombinant Anti-IL1 receptor antagonist | SQ, 4–6 h |
[Rheumatoid arthritis] |
| Rituximab (2006) |
Rituxan | Anti-CD20 therapy | IV, 14–62 days |
[Rheumatoid arthritis, non-Hodgkin lymphoma] |
| Tocilizumab (2010) |
Actemra | Anti-IL6 humanized monoclonal antibody | IV, 8–14 days |
[Rheumatoid arthritis] |
| Ustekinumab (2013) |
Stelara | Anti-IL12 and IL23 humanized monoclonal antibody | SQ, 20–24 days |
[Psoriatic arthritis, plaque psoriasis] |
| Canakinumab (2009, 2013) |
Ilaris | Anti-IL1B human monoclonal antibody | SQ, 26 days |
CAPS Juvenile idiopathic arthritis |
| Natalizumab (2008, 2013) |
Tysabri | Humanized anti integrin alpha 4 subunit monoclonal antibody (reduces leukocyte adhesion and transmigration) | IV, 11 days |
[Crohn's disease multiple sclerosis] |
| Belimumab (2011) |
Benlysta | Human IgG1λ monoclonal antibody against soluble human B lymphocyte stimulator protein | IV, 19 days |
[Systemic lupus erythematosus] |
| Rilonacept (2008, Orphan Drug) |
Arcalyst | IL1 receptor fusion protein | SQ, 8.6 days |
CAPS |
| Tofacitinib 2012 |
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.
