What is the risk of infections with Apremilast (Otezla), an immunosuppressant?

From the Guidelines

Apremilast is not an immunosuppressant medication in the traditional sense and does not significantly increase the risk of infections. Unlike many other medications used for psoriasis and psoriatic arthritis, apremilast works by inhibiting phosphodiesterase 4 (PDE4), which regulates inflammatory mediators within cells. This mechanism is more targeted and does not broadly suppress the immune system like biologics or traditional immunosuppressants.

Key Points

• Clinical trials and post-marketing surveillance have shown that apremilast does not significantly increase infection rates compared to placebo 1.
• Patients taking apremilast do not require special infection monitoring, tuberculosis screening, or vaccination considerations that are typically needed with immunosuppressive therapies.
• This favorable safety profile regarding infections makes apremilast a suitable option for patients who have recurrent infections or are at higher risk for infections.
• Common side effects of apremilast include gastrointestinal symptoms like diarrhea and nausea, headache, and weight loss, rather than infection-related complications.

Considerations

• Apremilast may be used instead of a TNFi biologic if the patient prefers an oral therapy or has contraindications to TNFi 1.
• Apremilast may be used in patients who prefer oral therapy or who have recurrent infections or contraindications to TNFi biologics 1.
• The most common adverse effects of apremilast are diarrhea, nausea, upper respiratory tract infections, and headache 1.

Dosage and Administration

• Patients should initially start at a lower dose (10 mg), which is titrated up over 5 days to reduce the risk of gastrointestinal adverse effects 1.
• Apremilast is dosed 30 mg by mouth twice daily after the initial titration period 1.
• Apremilast should be reduced to 30 mg once daily in patients with severe renal impairment (creatine clearance < 30 mL/min) 1.

From the FDA Drug Label

Diarrhea, nausea, and upper respiratory tract infection were the most commonly reported adverse reactions. The most common adverse reactions leading to discontinuation for subjects taking apremilast were nausea (1.6%), diarrhea (1.0%), and headache (0. 8%). Upper respiratory tract infection 31 (6) 84 (9)

Apremilast may increase the risk of infections, particularly upper respiratory tract infections.

• The most common infections reported were upper respiratory tract infections, which occurred in 9% of subjects taking apremilast compared to 6% of subjects taking placebo 2.
• Apremilast is not an immunosuppressant in the classical sense, but it may increase the risk of infections due to its mechanism of action as a phosphodiesterase 4 inhibitor 2.
• Patients taking apremilast should be monitored for signs of infection and discontinuation of apremilast should be considered if a serious infection occurs 2.

From the Research

Apremilast Infections and Immunosuppressant

• Apremilast is an oral phosphodiesterase inhibitor used to treat moderate to severe psoriasis in adults 3.
• The most commonly reported adverse events with apremilast include diarrhea, headache, nausea, nasopharyngitis, and upper respiratory tract infection 4, 5.
• Apremilast has been found to be a safe and efficacious drug for moderate-to-severe psoriasis, with most patients adhering to the therapy despite minor side effects 3.
• Common side effects of apremilast can be easily managed with interventions available to dermatologists, and rarely require dose adjustment or discontinuation of therapy 6.
• Apremilast modulates the immune system by increasing the levels of intracellular cyclic adenosine monophosphate (cAMP) and inhibiting IL-2 & 8, interferon-γ and tumor necrosis factor (TNF) production, which may contribute to its immunosuppressant effects 7.

Immunosuppressant Effects

• Apremilast's mechanism of action involves the inhibition of phosphodiesterase-4 enzyme, which modulates the immune system 7.
• Apremilast has been used off-label to treat various dermatological diseases where systemic corticosteroids or immunosuppressive agents were not effective 7.
• The immunosuppressant effects of apremilast may increase the risk of infections, such as upper respiratory tract infections and nasopharyngitis, which are commonly reported adverse events 4, 5.

Infection Risk

• The rate of adverse events, including infections, recorded in clinical practice series has been lower compared to clinical trials 5.
• Apremilast has demonstrated good safety and tolerability in both clinical trials and clinical practice series, with no significant increase in serious infections reported 3, 5.
• However, patients taking apremilast should be monitored for signs of infection, and the drug should be used with caution in patients with a history of recurrent infections 6.