Pharmacokinetics: Certolizumab is given subcutaneously and has a half-life of 14 days. Methotrexate decreases the appearance of anti-certolizumab antibodies. The usual dose for RA is 400 mg initially and at weeks 2 and 4, followed by 200 mg every other week, or 400 mg every 4 weeks.
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Indications: Certolizumab is indicated for the treatment of adults with moderately to severely active RA. It can be used as monotherapy or in combination with nonbiologic DMARDs. Additionally, certolizumab is approved in adult patients with Crohn’s disease, active PsA, and active AS. The certolizumab head-to-head TNFi trial, Exxelerate (NCT01500278), was a multicenter, single-blind, 24-month, randomized, parallel-group trial in moderate to severe MTX-incomplete-responder RA patients, comparing adalimumab + MTX to certolizumab
MTX. ACR20 responses at 3 months and achievement of low disease activity at 2 years were numerically comparable for both protocols. Although putatively a 24-month trial, patients could switch from one regimen to the other at 3 months, confounding comparability beyond that time frame. Not surprisingly, given this confounding, the primary goal of certolizumab
MTX superiority was not met. Patients were switched without washout so blood levels of TNFis as a group could be expected to be very high during the switchover. Interestingly, no serious infectious events occurred during the switch-over period.
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Mechanism of Action: Etanercept is a recombinant fusion protein consisting of two soluble TNF p75 receptor moieties linked to the Fc portion of human IgG1 (Figure 36–4); it binds TNF-α molecules and also inhibits lymphotoxin α.
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Pharmacokinetics: Etanercept is given subcutaneously as 25 mg twice weekly or 50 mg weekly. In psoriasis, 50 mg is given twice weekly for 12 weeks and then is followed by 50 mg weekly. The drug is slowly absorbed, with peak concentration 72 hours after drug administration. Etanercept has a mean serum elimination half-life of 4.5 days. A recent study demonstrated a reduction of radiographic progression with the use of 50 mg of etanercept weekly.
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Indications: Etanercept is approved for the treatment of RA, juvenile chronic arthritis, psoriasis, PsA, and AS. It can be used as monotherapy, although over 70% of patients taking etanercept are also using methotrexate. Etanercept decreases the rate of formation of new erosions relative to methotrexate alone. It is also being used in other rheumatic syndromes such as scleroderma, granulomatosis with polyangiitis (Wegener’s granulomatosis), giant cell arteritis, Behçet’s disease, uveitis, and sarcoidosis. However, a comparative study of ustekinumab (an IL-12 and IL-23 blocker) and etanercept concluded that ustekinumab at a dose of 45 or 90 mg was superior to high-dose etanercept (50 mg twice weekly) over a 12-week period in patients with psoriasis.
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Mechanism of Action: Golimumab is a human monoclonal antibody with a high affinity for soluble and membrane-bound TNF-α. Golimumab effectively neutralizes the inflammatory effects produced by TNF-α seen in diseases such as RA.
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