Table II.

Overview of biologics used in the treatment of RA.

Drug class	Drug (US FDA approval date)	Structure	Mode of action	Dose and route of administration	Half-life	Acquisition cost^a
Currently available treatments
TNF antagonist	Etanercept (1998)²⁰	Soluble fusion protein (dimer) of 2 recombinant p75 TNF-α receptor proteins, with each molecule linked to the Fc portion of human IgG1	Prevent binding of TNF-α to its receptor	SC injection of 25 mg twice weekly or 50 mg once weekly (self-administered)	4 days	$1,664
	Infliximab + MTX (1999)²¹	Chimeric MAB with Fc region of human IgG1 joined to variable region of mouse anti-TNF-α antibody		IV infusion of 3 mg/kg over 2 hours at weeks 0, 2, 6, then every 8 weeks, with dose adjustment up to 10 mg/kg if necessary	8–10 days	$1,109–$5,435
	Adalimumab (2002)²²	Recombinant human IgG1 MAb to TNF-α		SC injection of 40 mg every 2 weeks (self-administered)	14 days	$1,633
	Certolizumab pegol (2009)²⁶	Pegylated humanized monoclonal anti-TNF Fab’ fragment		SC (liquid or lyophilized) injections of 400 mg at weeks 0, 2, and 4, followed by 200 mg every other week (or 400 mg every 4 weeks)	14 days	$1,567
	Golimumab + MTX (2009)²⁷	Human anti-TNF receptor MAb		SC injection of 50 mg once a month	~14 days	$1,575
IL-1 inhibitor	Anakinra (2001)²³	Recombinant IL-1 inhibitor	Prevents IL-1 from binding to its receptor	SC injection of 100 mg daily	4–6 hours	$1,363
T-cell co-stimulation blocker	Abatacept (2005)²⁴	Recombinant fusion protein consisting of the extracellular domain of human CTLA-4 and part of the Fc domain of human IgG1	Prevents the costimulatory signal required for T-cell activation	IV infusion of 500–1000 mg over 30 minutes, depending on bodyweight, at weeks 0, 2, and 4, then every 4 weeks	17 days	$1,056–$2,112
B-cell targeted therapy	Rituximab + MTX (2006)²⁵	Chimeric human/mouse anti-CD20 MAb	Binds to CD20, a cell marker expressed on mature- and pre-B cells, but not on other cells, including plasma cells; leads to selective depletion of CD20+ B cells via several mechanisms	Two separate 1000-mg IV infusions, 2 weeks apart (IV methylprednisolone 100 mg or equivalent is recommended 30 minutes before rituximab to prevent serious reaction)	19 days	$1,845
Biologics newly approved in the US
IL-6 inhibitor	Tocilizumab (approved 2010)	Humanized anti-IL-6 receptor MAb	Prevents IL-6 from binding to both membrane-expressed and soluble IL-6 receptors	IV infusions of 4 mg/kg or 8 mg/kg every 4 weeks as monotherapy or in combination with DMARDs
RANKL inhibitor	Denosumab (phase II)^b	Human anti-RANKL MAb	Binds RANKL and inhibits RANKL action	SC twice-yearly injections of denosumab plus MTX

Estimated based on vial prices 11/11/2009 and WAC from First Data Bank in US dollars.¹¹⁰ The following assumptions were made: dosing based on FDA-approved labels; proprietary concessions not considered; 1 month = 30 days; average infliximab patient weighs 80 kg; maintenance dosing (not loading dose) was used; for products dosed <1× per month, monthly cost = 1/12 × annual cost; infliximab upper bound cost = 10 mg every 4 weeks; rituximab readministered at 6 months; does not include cost of concurrent medication such as MTX or infusion supplies.

Denosumab is approved in the US for the treatment of postmenopausal osteoporosis (approved June 2010) but is not currently indicated for the treatment of rheumatoid arthritis.

DMARDs = disease-modifying antirheumatic drugs; IgG = immunoglobulin; IL = interleukin; IV = intravenous; MAb = monoclonal antibody; MTX = methotrexate; RA = rheumatoid arthritis; RANKL = receptor-activator of NF-κB ligand; SC = subcutaneous; TNF = tumor necrosis factor; US FDA = United States Food and Drug Administration; WAC = wholesale acquisition cost