DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 65–10
Biological Agents Commonly Used in Dermatology
DRUG ALEFACEPT EFALIZUMAB ADALIMUMAB ETANERCEPT INFLIXIMAB
Structural class Receptor- Humanized Human Receptor-antibody Chimeric monoclonal
antibody monoclonal monoclonal fusion protein antibody
fusion antibody antibody
protein
Components LFA-3 and Complementarity IgG1 p75 TNF receptor Variable region of mouse
Fc IgG1 determining region and Fc IgG1 monoclonal antibody on
of mouse monoclonal
human IgG1
antibody on human IgG 1
Binding site CD2 CD11a subunit of LFA-1 TNF- TNF- TNF-
Method of IM SC SC SC IV
administration
Dosing for 15 mg 0.7 mg/kg first week, 80-mg loading 50 mg twice 5 mg/kg at weeks 0, 2,
psoriasis weekly × then 1 mg/kg weekly dose, then 40 weekly × 3 , and 6, then every
12 weeks, mg biweekly months then 6-8 weeks
stop 12
50 mg weekly
weeks, then
repeat
FDA indications Moderate- Moderate-severe Moderate-severe Moderate- Severe psoriasis;
severe psoriasis psoriasis; severe psoriasis; moderate-severe
psoriasis moderate- moderate- psoriatic arthritis; adult
severe psoriatic severe psoriatic rheumatoid arthritis;
arthritis; adult arthritis; ankylosing spondylitis;
and juvenile adult and juvenile ulcerative colitis;
rheumatoid rheumatoid Crohn’s disease
arthritis; arthritis;
ankylosing ankylosing
spondylitis; spondylitis
Crohn’s disease
Pregnancy B C B B B
category
Efficacy in 28-33% 27-39% 53% 47% 76-80%
psoriasis a
a
Probability (%) of Psoriasis Area and Severity Index (PASI) score of 75 after 12 weeks of therapy at the dosing described in the table (Tzu and
Kerdel, 2008). LFA, lymphocyte function–associated antigen; IgG, immunoglobulin G; TNF, tumor necrosis factor; IM, intramuscular;
SC, subcutaneous; IV, intravenous.
Efalizumab. Efalizumab (RAPTIVA) is a humanized monoclonal
antibody against the CD11a molecule of LFA-1. By
binding to CD11a on T cells, efalizumab prevents binding
of LFA-1 to intercellular adhesion molecule (ICAM)-
1 on the surface of antigen-presenting cells, vascular
endothelial cells, and cells in the dermis and epidermis
(Figure 65–5), thereby interfering with T-cell activation
and migration and cytotoxic T-cell function (Weinberg,
2003). A transient peripheral leukocytosis occurs in some
patients taking efalizumab, which may be due to the inhibition
of T-cell trafficking. Other side effects include
thrombocytopenia, exacerbation of psoriasis, and rebound
psoriasis upon discontinuation. Therefore, CBCs should
be obtained at baseline and periodically thereafter. Recent
reports have implicated efalizumab in the development of
PML, and extra caution should be exercised in patients
who develop neurological signs while on efalizumab
(Castelo-Soccio and Van Voorhees, 2009).
Tumor Necrosis Factor Inhibitors
TNF-, produced by macrophages, T cells, dendritic
cells, and keratinocytes, is elevated in both the lesions