Latest Treatments for Psoriatic Arthritis
Ustekimumab and apremilast are welcomed second-line treatment options for PsA
Psoriatic arthritis (PsA) is a chronic, autoimmune, inflammatory form of arthritis that causes painful, swollen joints, as well as the skin symptoms associated with psoriasis. Approximately 30 percent of people with psoriasis develop PsA in addition to their skin condition. Treatment goals are to improve both joint and skin symptoms, as well as to prevent permanent joint damage.
Depending on its severity, psoriatic arthritis is treated with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. Biologics such as adalimumab (Humira), etanercept (Enbrel), golimumab (Simponi) and infliximab (Remicade) also are used when other treatments fail to bring relief. Despite effective treatment, many psoriatic arthritis patients are undertreated. Two drugs have recently been approved for use in psoriatic arthritis, increasing doctors’ and patients’ treatment options.
Ustekimumab Therapy for Psoriatic Arthritis
In September 2013, the U.S. Food and Drug Administration (FDA) approved the biologic ustekinumab (Stelara) for the treatment of moderate to severe psoriatic arthritis (PsA) in adult patients. Ustekimumab can be used alone or with methotrexate, giving PsA patients who haven’t responded to existing treatments another option. It was first approved in 2009 for the skin disease psoriasis. Unlike anti-TNFs, ustekinumab targets two other molecules involved in inflammation, interleukin-12 (IL-12) and interleukin-23 (IL-23).
“Some patients don’t do well with available drugs, so I’m glad we have another choice,” says Joseph F. Merola, MD, co-director of the center for skin and related musculoskeletal diseases at Brigham and Women's Hospital in Boston. “It’s not uncommon to see patients who have been through several first-line therapies and hit a wall when we run out of options, so it’s important for us to have new treatments,” he says.
The FDA based its approval on two phase III, randomized, double blind, placebo-controlled trials of more than 900 patients. The study participants had at least five tender and swollen joints and high levels of C-reactive protein (a measure of inflammation), and weren’t responding to current therapies.
As many as half the patients receiving the drug enjoyed at least a 20 percent improvement in symptoms, as measured by American College of Rheumatology criteria.
Ustekinumab helped PsA patients with symptoms ranging from joint pain and dactylitis (the inflammation of an entire finger or toe, known as “sausage digit”) to skin and soft tissue problems. The dosing regimen is also appealing to patients; after two starter doses, it’s given once every three months. Its side effects, including a higher risk of infection, are similar to those of other biologics.
Ustekimumab is not a first-line drug for PsA patients, and won’t be until doctors learn more about how well it works in PsA in the long-term. “I don’t think anyone will stop their current therapy… but I suspect this will be a very solid second-line agent,” says Dr. Merola.
Apremilast Therapy for Psoriatic Arthritis
In March 2014, the FDA approved the oral medication apremilast (Otezla) for clinically active psoriatic arthritis. Apremilast selectively blocks phosphodiesterase 4 (PDE4), an enzyme involved in inflammation.
“This is an additional treatment option for psoriatic arthritis, which is always a good thing because everyone responds differently to their medications,” says John Hardin, MD, rheumatologist and professor of medicine at Albert Einstein College of Medicine in New York.
In one phase 3 clinical trial, people treated with apremilast showed significant improvement in signs and symptoms of psoriatic arthritis - including tender and swollen joints, physical function and skin symptoms - after 16 weeks on the drug. Up to 40 percent of patients saw at least a 20 percent improvement as measured by the American College of Rheumatology response criteria compared with 19 percent of patients who took a placebo.
Doctors might use apremilast to treat people who have failed to see benefits from other drugs, or they might prescribe it earlier in the course of the disease. “It could be considered as a first-line therapy given its efficacy and safety profile,” says Philip Mease, MD, director of rheumatology research at Swedish Medical Center and clinical professor at University of Washington School of Medicine in Seattle.. “However, in reality, given considerations of cost and the fact that it is new, most formulary managers at insurance companies as well as programs such as Medicare and Medicaid will likely request that clinicians first try a generic therapy such as methotrexate.”
Unlike most biologic drugs, apremilast does not appear to increase the risk of serious infections. Side effects include diarrhea and nausea, which tend to be mild-to-moderate and may improve with continued use.