Pharmacokinetics: Golimumab is administered subcutaneously and has a half-life of approximately 14 days. Concomitant use with methotrexate increases golimumab serum levels and decreases anti-golimumab antibodies. The recommended dose for the treatment of RA, PsA, and AS is 50 mg given every 4 weeks. A higher dose of golimumab is used for the treatment of ulcerative colitis as follows: 200 mg initially at week 0 followed by 100 mg at week 2 and every 4 weeks thereafter.
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Indications: Golimumab with methotrexate is indicated for the treatment of moderately to severely active RA in adult patients. It is also indicated for the treatment of PsA and AS and moderate to severe ulcerative colitis.
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Mechanism of Action: Infliximab (Figure 36–4) is a chimeric (25% mouse, 75% human) IgG1 monoclonal antibody that binds with high affinity to soluble and possibly membrane-bound TNF-α. Its mechanism of action probably is the same as that of adalimumab.
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Pharmacokinetics: Infliximab is given as an intravenous infusion with “induction” at 0, 2, and 6 weeks and maintenance every 8 weeks thereafter. Dosing is 3–10 mg/kg, and the usual dose is 3–5 mg/kg every 8 weeks. There is a relationship between serum concentration and effect, although individual clearances vary markedly. The terminal half-life is 9–12 days without accumulation after repeated dosing at the recommended interval of 8 weeks. After intermittent therapy, infliximab elicits human antichimeric antibodies in up to 62% of patients. Concurrent therapy with methotrexate markedly decreases the prevalence of human antichimeric antibodies.
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Indications: Infliximab is approved for use in RA, AS, PsA, Crohn’s disease, ulcerative colitis, pediatric inflammatory bowel disease, and psoriasis. It is being used off-label in other diseases, including granulomatosis with polyangiitis (Wegener’s granulomatosis), giant cell arteritis, Behçet’s disease, uveitis, and sarcoidosis. In RA, infliximab plus methotrexate decreases the rate of formation of new erosions. Although it is recommended that methotrexate be used in conjunction with infliximab, a number of other nonbiologic csDMARDs, including antimalarials, azathioprine, leflunomide, and cyclosporine, can be used as background therapy for this drug. Infliximab is also used as monotherapy.
Adverse Effects of TNF-`-Blocking Agents
TNF-α–blocking agents have multiple adverse effects in common. The risk of bacterial infections and macrophage-dependent infection (including tuberculosis, fungal, and other opportunistic infections) is increased, although it remains very low. Activation of latent tuberculosis is lower with etanercept than with other TNF-α–blocking agents. Nevertheless, all patients should be screened for latent or active tuberculosis before starting TNF-α– blocking agents. The use of TNF-α–blocking agents is also associated with increased risk of HBV reactivation; screening for HBV is important before starting the treatment.
TNF-α–blocking agents increase the risk of skin cancers— including melanoma—which necessitates periodic skin examination, especially in high-risk patients. On the other hand, there is no clear evidence of increased risk of solid malignancies or lymphomas with TNF-α–blocking agents, and their incidence may not be different compared with other bDMARDs or active RA itself.