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    Off-label systemic immunomodulators useful for various indications

    Off-label systemic immunomodulators useful for various indications

    Denver — Although many systemic immunomodulators are approved for psoriasis, their mechanisms of action suggest they have utility in indications ranging from atopic dermatitis (AD) to chronic urticaria, according to an expert.

    Understanding a systemic immunomodulator’s mechanism of action provides a theoretical basis for uses beyond its labeled indication, says Neal Bhatia, M.D., a dermatologist in private practice in Long Beach, California, and an associate professor of dermatology at the Harbor University of California Los Angeles Medical Center.

    “Apremilast will be marketed for psoriatic arthritis, but its utility in discoid lupus and atopic dermatitis could be substantial,” he says.

    RELATED: Gene helps confirm existence of psoriatic arthritis

    Improving AD severity

    Case reports in AD show that apremilast reduces pruritus and disease severity and helps maintain disease control, he says.

    Apremilast inhibits phosphodiesterase-4 (PDE4), which exerts its impact upstream of proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-17a, Dr. Bhatia says.

    “In terms of the Th1 profile in psoriasis, if you slow the progression that produces those cytokines and proteins, you can reduce inflammation,” he says.

    Along with impacting the expression and actions of cyclic adenosine monophosphate (cAMP), protein kinase A and nuclear factor (NF)-kB, he adds, “Apremilast works on pathways that are much broader and can encompass the Th2 side of inflammation, which was shown in a 16-patient pilot study involving AD.1

    RELATED: Study: CME improves psoriasis care

    In this study, patients who took 20mg doses of apremilast twice daily achieved significant reductions in baseline pruritus scores (p=0.02) and the Dermatology Life Quality Index (DLQI; p=0.003) at three months. Patients who took twice-daily 30mg doses achieved significant reductions in DLQI (p=0.01) and Eczema Area and Severity Index (EASI; p=0.008) scores at three months. At six months, investigators observed significant reductions in DLQI, EASI and visual analog scores.

    “In AD, we need the fire not only to be put out, but also kept out. That’s where the sustained anti-inflammatory activity of apremilast can help,” Dr. Bhatia says. As eczema shifts from acute to chronic, the Th profile shifts. Initially, “Th2 predominates. Then, as lymphocytes come in and the disease becomes expressed, there is more Th1 immunity later on. So it’s important to catch the disease early. And apremilast has shown it has that potential because it changes the immune makeup early in the disease. AD is a good example of an off-label application that might skyrocket use of apremilast.”

    NEXT: Use in lichen planus

    John Jesitus
    John Jesitus is a medical writer based in Westminster, CO.

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