A low incidence of newly formed dsDNA antibodies and antinuclear antibodies (ANAs) has been documented when using TNF-α–blocking agents, but clinical lupus is extremely rare and the presence of ANA and dsDNA antibodies per se does not contraindicate the use of TNF-α–blocking agents. In patients with borderline or overt heart failure (HF), TNF-α–blocking agents can exacerbate HF. TNF-α–blocking agents can induce the immune system to develop antidrug antibodies in about 17% of cases. These antibodies may interfere with drug efficacy and correlate with infusion site reactions. Injection site reactions occur in 20–40% of patients, although they rarely result in discontinuation of therapy. Cases of alopecia areata, hypertrichosis, and erosive lichen planus have been reported. Cutaneous pseudo-lymphomas are reported rarely with TNF-α–blocking agents, especially infliximab. TNF-α–blocking agents may increase the risk of gastrointestinal ulcers and large bowel perforation including diverticular and appendiceal perforation.
Nonspecific interstitial pneumonia, psoriasis, and sarcoidosislike syndrome are among the rare reported toxicities associated with TNF-α blockers. Rare cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia have also been reported. The precipitating drug should be discontinued in such cases.
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Mechanism of Action: Ustekinumab is an IL-12 and IL-23 antagonist. It is a fully human IgG monoclonal antibody to the p40 protein subunit, which is part of both IL-12 and IL-23. These two cytokines are important contributors to the chronic inflammation in psoriasis plaques, PsA, and Crohn’s disease. Ustekinumab prevents the binding of the p40 subunit of both IL-12 and IL-23 to the IL-12 receptor b1 found on the surface of CD4 T cells and NK cells. This interruption interferes with IL-12 and IL-23 signal transduction and suppresses the formation of proinflammatory TH1 and TH17 cells.
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Pharmacokinetics: Ustekinumab is available as a 45and 90-mg SC injection for PsA and plaque psoriasis. Its bioavailability is 57% following SC injection; time to peak plasma concentration is 7–13.5 days and elimination half-life is 10–126 days. For adults with PsA, a loading dose at 0 and 4 weeks is followed by maintenance doses once every 12 weeks. IV infusion as a 130 mg dose is available for Crohn’s disease.
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Indications: Ustekinumab is indicated for treatment of adult patients with PsA. It can be used as monotherapy or in combination with methotrexate. Other indications include plaque psoriasis and Crohn’s disease.
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Adverse Effects: Upper respiratory tract infection is the most common side effect, but rare severe infection, malignancy, and reversible posterior leukoencephalopathy syndrome have been reported. Ustekinumab should be discontinued at least 15 weeks before live vaccines are administered and can be resumed at least 2 weeks after.
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Mechanism of Action: Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the IL-17A cytokine, inhibiting its interaction with the IL-17A receptor. IL-17A is involved in normal inflammatory and immune responses. Elevated concentrations of IL-17A are found in psoriatic plaques and PsA.
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