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Treatment of psoriatic arthritis reflects the fact that the disease has elements in common with both skin psoriasis and RA. Optimal psoriatic arthritis (PsA) treatment benefits from cooperation between dermatologists (experts in skin disease) and rheumatologists (experts in arthritis).
Non-steroidal Anti-inflammatory Drugs (NSAIDs)
Generic Name (Brand Names)
Ibuprofen (Advil, Motrin, others)
Naproxen (Aleve and others)
Indomethacin (Indocin and others)
Diclofenic (Voltaren and others)
Celecoxib (Celebrex)
Non-prescription NSAIDs such as ibuprofen and naproxen reduce inflammation and relieve pain. They are a first line treatment for many types of arthritis, including PsA. More powerful prescription NSAIDs such as indomethacin and diclofenic are also available. These drugs are appropriate for mild to moderate cases of PsA, in which no structural damage to the joints is visible by X-ray or other imaging methods. Some patients need to stop taking these medications due to gastrointestinal side effects including nausea, ulceration, and bleeding.
Celecoxib is a prescription NSAID that belongs to a family of dugs known as selective COX-2 inhibitors. It has the anti-inflammatory effects of other NSAIDs while being less likely to cause gastrointestinal side effects. Currently available only in the brand name form, Celebrex, celecoxib is very expensive compared to many other NSAIDS.
Long-term use of high-doses of NSAIDs appears to increase the risk of heart attack and stroke. Although the issue is still controversial and somewhat murky, the risk probably applies, in varying degrees, to all NSAIDs. NSAIDs carry an FDA mandated warning about possible cardiovascular effects. Another COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market by its maker, Merck & Co., in 2004 because of an association with heart attacks and strokes.
Traditional Disease Modifying Anti-Rheumatic Drugs (DMARDs)
DMARDs such as methotrexate, cyclosporine, sulfasalazine, and leflunomide are called “traditional” or “conventional” to distinguish them from the newer biologic DMARDs (see below). With the exception of leflunomide, which was FDA approved in 2005, they have been used to treat PsA and RA for decades. They are offered to patients whose arthritis pain does not respond to NSAIDs or who have progressive structural joint damage. All of these drugs most likely inhibit the abnormal immune response that is the root cause of PsA, but their exact mechanisms of action are not well understood. Many health insurance companies require PsA patients to try a course of therapy with a traditional DMARD, usually methotrexate, before agreeing to pay for biologic therapy.
Methotrexate and Cyclosporine
Methotrexate and cyclosporine have a long history of use in treating both skin psoriasis and PsA. (Read more about methotrexate and cyclosporine as psoriasis treatments.) Their effectiveness against PsA has been determined for the most part by years of informal clinical practice, rather than through controlled research studies, so it is difficult to say exactly how well they work. Cyclosporine is the better studied of the two. It outperformed standard therapy (NSAIDs, pain relievers, and/or prednisone, a corticosteroid) in relieving joint pain, swelling, and tenderness. A study comparing methotrexate and cyclosporine in 35 patients with PsA found that they were both effective at reducing pain and swelling in joints, decreasing the duration of morning stiffness, and improving grip strength in arthritic joints. Methotrexate does not appear to slow the progression of structural joint damage; a small study hinted that cyclosporine might be more effective in this capacity. Both drugs can be very toxic—methotrexate to the liver and cyclosporine to the kidneys—so patients taking them must be carefully monitored for organ damage. In fact, cyclosporine usually cannot be used for extended periods of time.
Sulfasalazine
Sulfasalazine is a sulfa drug, related to the sulfa antibiotics. First used to treat RA, it is now used to treat a number of inflammatory diseases including PsA. It has been well tested in clinical trials and has proved to be modestly but consistently effective. Joints in the arms and legs may respond better to sulfasalazine treatment than those in the spine. The side effects of sulfasalazine are usually mild. Nausea is common, but more serious gastrointestinal problems are less common than with NSAIDS. People who have an allergy to sulfa antibiotics should discuss with their doctor whether or not it is safe to take sulfasalazine.
Leflunomide
Leflunomide, a new drug that gained FDA approval for the treatment of RA in 2005, has also been shown to be effective against PsA in a recent clinical trial. There are also hints from clinical practice that leflunomide might inhibit joint damage caused by PsA. Leflunomide works by reducing inflammation, but no one understands as yet exactly how. It is known to interfere with the production of DNA, which could prevent some cells in the immune system from dividing. On the safety side, leflunomide has the potential to cause severe liver damage, although no serious liver problems occurred during the PsA trial. Also, leflunomide may cause birth defects, so women should not become pregnant while taking the drug or within two years after stopping it.
The Biologics (aka Biologic Response Modifiers or Biologic DMARDs)
Over the past several years the FDA has approved several biologic agents for the treatment of PsA, skin psoriasis, RA, and a number of other inflammatory diseases. These agents, which are derivatives of human or animal protein molecules, inhibit specific components of the immune system that contribute to prolonged inflammation. Some of the biologics have been impressively effective in clinical trials, and serious side effects have been rare. However, there are two significant downsides to the biologics: One is cost—a year’s worth of treatment can cost from $10,000 - $30,000, out of reach for anyone who does not have good health insurance. The other is the uncertainty about whether long-term risks may emerge after decades of use, or decades after use (since the biologics have emerged only in the last 10 years). (Click here for detailed information on biologics for the treatment of psoriasis.) The biologics used to treat PsA target either TNF-alpha (etanercept/Enbrel, infliximab/Remicade, and adalimumab/Humira) or T cells (alefacept/Amevive and efalizumab/Raptiva). The TNF-alpha inhibitors have shown particularly strong results for psoriatic arthritis.
TNF-alpha Inhibitors
Generic Name (Brand Name)
Etanercept (Enbrel)
Infliximab (Remicade)
Adalimumab (Humira)
Etanercept, infliximab, and adalimumab have all proven to be very effective against PsA when compared to placebo in clinical trials in reducing the signs and symptoms of psoriatic arthritis (both skin and joint symptoms) and improving physical function of psoriatic arthritis patients. Importantly, all three treatments have also been shown for many patients to prevent bones and joints affected by psoriatic arthritis from getting worse. We believe this is a very important consideration for psoriatic arthritis patients, particularly those who have evidence of permanent damage from PsA. These patients now have FDA-approved options that may slow or prevent further damage from PsA.
T cell Inhibitors
Generic Name (Brand Name)
Alefacept (Amevive)
Efalizumab (Raptiva)
Both agents are FDA approved for the treatment of skin psoriasis and clinical trials in PsA patients are underway. In a 24-week long Phase II clinical trial, alefacept was significantly superior to placebo in treating PsA. So far, efalizumab has not fared so well. It did not perform significantly better than placebo in a 12 week trial. Researchers are investigating whether efalizumab might be more effective if used for a longer time.
Other possible options
Generic Name (Brand Name)
Abatacept (Orencia)
Ustekinumab/CNTO 1275 (None yet)
When other treatments fail for psoriatic arthritis, physicians consider whether treatments approved for other diseases may work for PsA. Treatments for rheumatoid arthritis are often the first place physicians look in such cases. One RA treatment that is receiving attention as a potential treatment for psoriatic arthritis is abatacept (brand name Orencia). Previously, a small, Phase Two clinical trial found abatacept effective at treating psoriasis. Now, patients are being gathered for an upcoming Phase Two clinical trial to test abatacept in psoriatic arthritis. Psoriasis Cure Now advocated before the U.S. Food and Drug Administration in 2005, urging abatacept’s approval for rheumatoid arthritis, precisely because it may prove effective in practice for psoriasis and/or psoriatic arthritis, giving patients an additional treatment option. (Abatacept works differently than existing biologics for PsA.)
Another novel treatment that is currently being reviewed by the FDA is ustekinumab (also known as CNTO 1275). It, too, works differently than existing biologics (including abatacept). In Phase Three clinical trials, ustekinumab proved effective as a psoriasis treatment, and is currently in a Phase Two trial for psoriatic arthritis. FDA approval for ustekinumab for moderate to severe psoriasis could come as early as December 2008. (Once FDA-approved for psoriasis, doctors would be permitted to prescribe it for patients with other diseases, including psoriatic arthritis, although such “off label” use is not often done with brand new treatments.)
The treatment pipeline
The biotechnology and pharmaceutical industries are curently investigating more than 70 new potential psoriasis and/or psoriatic arthritis treatments! So our treatment arsenal is expected to grow further in the coming years. The psoriasis community should keep pushing for additional treatments and improved access to proven therapies until every psoriasis and psoriatic arthritis patient finds relief.
Treatment for psoriatic arthritis has improved dramatically in the last decade. Everyone who has or may have psoriatic arthritis should discuss treatment options with their physician. Permanent joint damage is no longer inevitable. But too many people are still suffering. The battle is not over yet.
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Back to the Psoriatic Arthritis Info Center.
Selected References
Furfaro, N. "Diagnostic Signs and Symptoms of Psoriatic Arthritis." Dermatology Nursing. 2006 Oct;Suppl:7-9, 22.
Gladman, DD. "Clinical, radiological, and functional assessment in psoriatic arthritis: is it different from other inflammatory joint diseases?" Annals of the Rheumatic Diseases. 2006 Nov;65 Suppl 3:iii22-4.
Lee, MR and Cooper, AJ. "Immunopathogenesis of psoriasis." Australasian Journal of Dermatology. 2006 Aug;47(3):151-9.
Mease, P. "Current Treatment for Psoriatic Arthritis and Other Spondyloarthritides." Rheumatic Disease Clinics of North America. 2006 Dec;32 Suppl 1:11-20.
Soriano, ER and McHugh, NJ. "Therapies for Peripheral Joint Disease in Psoriatic Arthritis. A Systematic Review." The Journal of Rheumatology. 2006 Jul;33(7):1422-30.
Turkiewicz, AM and Moreland, LW. "Psoriatic Arthritis: Current Concepts on Pathogenesis-Oriented Therapeutic Options." Arthritis & Rheumatism. 2007 Apr;56(4):1051-66.
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