A Closer Look At Current Biologics For Psoriasis

Approximately 2 percent of the U.S. population have psoriasis, which can affect skin, nails and joints. Therapies include topical medications (such as corticosteroids and moisturizers), oral medications (methotrexate and cyclosporine) and phototherapy (PUVA and UVB). Targeted systemic therapies, typically known as “the biologics,” have been gathering momentum in the treatment of psoriasis. I have personally seen significant improvement in the quality of life for some of my patients on various biologics.

However, the point of this blog is not to encourage rapid prescription writing of these medications but rather to understand why a current patient would be prescribed a biologic therapy by a rheumatologist or a dermatologist.

Biologic therapies treat moderate to severe psoriasis in patients who have failed topical therapies and/or the oral systemic and phototherapies. Many of these medications also treat psoriatic arthritis. They can be used alone or in combination with other therapies like methotrexate, depending on the patient’s situation.

From a podiatric patient’s perspective, a manifestation of hand-foot plaque psoriasis that has failed first- and second-line therapies warrants biologic therapy. The presence of disabling dactylitis of the digits or enthesitis at the insertion of the Achilles tendon would also warrant biologic therapy. When considering biologic therapy, physicians must be intimately familiar with the patient’s medical history and order a series of laboratory tests as well as a PPD test prior to starting the medication. Physicians should also monitor these values during the course of treatment.

Over the last few years, the various cytokines in the inflammatory cascade of psoriasis have been targeted with these emerging therapies that can significantly decrease the presence of psoriatic plaques and joint tenderness.

Reviewing The Tumor Necrosis Factor Inhibitors

Infliximab (Remicade®, Centocor), etanercept (Enbrel®, Amgen/Wyeth) and adalimumab (Humira®, Abbott) are approved for use in treating psoriasis and psoriatic arthritis (PsA). The newly approved golimumab (Simponi™, Centocor Ortho Biotech) is indicated for active PsA.

Infliximab is a chimeric (mouse and human) monoclonal antibody that binds to both transmembrane and soluble TNF-α, which ultimately blocks the effects of the cytokine. Patients receive this medication as an infusion over several hours at certain weekly frequencies. Etanercept is a human fusion protein consisting of a TNF-α receptor and the Fc portion of IgG1, which binds to both membrane bound and soluble TNF-α. Prescribing physicians administer etanercept as a subcutaneous injection twice a week for 12 weeks. This regimen is followed by weekly injections that can be given at home.

Adalimumab is a human monoclonal anti-TNF-α antibody that binds to both membrane-bound and soluble TNF-α. Prescribing physicians initially provide a loading dose injected subcutaneously. This is followed by a lower dose the second week and subsequent injections every two weeks. Golimumab is another human monoclonal antibody that targets TNF-α and this is administered via subcutaneous injection once a month.

Other Emerging Biologic Agents

The t-cell inhibitor alefacept (Amevive®, Astellas Pharma) is approved for moderate to severe chronic plaque psoriasis. It is a fusion protein that binds to the CD2 on memory T-cells. This medication blocks the activation of these T-cells and ultimately reduces their number.

Recently, ustekinumab (Stelara™, Centocor Ortho Biotech) has been approved for chronic plaque psoriasis. It is a monoclonal antibody that blocks IL-12 and IL-23, and ultimately decreases T-cell differentiation into Th1 cells and Th17 cells. This exciting development in the psoriasis inflammatory pathway will be the target of many more biologic medications in the future.

Ultimately, these drugs have the potential of changing a patient’s quality of life in ways never thought imaginable. However, it is important as a podiatric practitioner to be familiar with these medications and be in contact with the prescribing physician when it comes to gauging how the patient will handle infection, surgery or newly diagnosed diseases on the lower extremity such as skin cancer or a rash that could be a drug reaction.

References

1. Gottlieb AB, Kardos M, Yee M. Current biologic treatments for psoriasis. Dermatology Nursing 2009:21(5); 259.
2. Menter A, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis, Section 1. JAAD 2008:58(5); 826.
3. Gottlieb A, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis, Section 2. JAAD 2008:58(5); 851.