Table II.
Drug class | Drug (US FDA approval date) | Structure | Mode of action | Dose and route of administration | Half-life | Acquisition costa |
---|---|---|---|---|---|---|
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