WAILEA, HAWAII – While psoriasis experts typically emphasize the disease’s chronic nature and the importance of effective long-term therapy, in reality the first big question when a patient presents to the office should be, ‘What’s the urgency of treatment?’ according to Dr. Kenneth B. Gordon, professor of dermatology at Northwestern University, Chicago.
Two patients can have equally extensive disease yet dissimilar treatment urgencies – and different treatments of choice as a result, he said at the Hawaii Dermatology Seminar, sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.
The list of preferred medications for patients with high treatment urgency is short: "When you need to get people better fast, infliximab and cyclosporine are the go-to drugs," the dermatologist stressed.
Insurance companies will often insist that a patient try methotrexate before resorting to a far costlier biologic agent. That’s unreasonable when the treatment urgency is high.
"Methotrexate doesn’t have a high enough level of predictability or efficacy of response. Additionally, it takes a long time to act. When someone is acutely ill, you don’t want to have to wait 16 weeks to figure out what’s the highest level of efficacy you’re going to get. You want to know that answer in 10 weeks, like you do with infliximab. Infliximab is a wonderful short-term therapy for patients who have urgent disease. And with cyclosporine you see effects in 4-8 weeks," Dr. Gordon continued.
He noted that in the open-label RESTORE 1 trial, in which 868 psoriasis patients were randomized to infliximab or methotrexate, the PASI-75 response rate at week 6 in the infliximab group was already close to 60%. By week 10, the PASI-75 rate was 75% in the infliximab group and 27% in the methotrexate group (Br. J. Dermatol. 2011;165:1109-17).
The main safety concern with cyclosporine is renal toxicity, which doesn’t emerge as a real problem until after about a year on the drug, Dr. Gordon said. The safety concerns associated with short-term use (6-8 weeks) to treat an acute exacerbation of psoriasis before transitioning to a different medication are modest, and limited to relatively uncommon increases in blood pressure.
Factors that might raise a patient’s treatment urgency level range from sleep deprivation because of psoriasis pain and itching to workplace hassles because of extensive sick leave, to an important public appearance scheduled within 6-8 weeks.
Session moderator Dr. Craig L. Leonardi remarked that getting payer approval for infliximab often takes a month.
"Unless you’re university based, it’s unlikely you’re going to get infliximab fast, so cyclosporine becomes a real mainstay of treatment when it’s hot and bothersome psoriasis," he said. "And it’s the treatment of choice for psoriasis during pregnancy, absolutely. It’s category C, but there’s a lot of experience with it in the transplant population," noted Dr. Leonardi of St. Louis University.
Dr. Gordon also described a clinical scenario completely different from high treatment urgency – the patient with extensive, yet stable disease. In such a case, the priority is to select a drug the patient can tolerate for a year or more, with good long-term safety and little loss of efficacy over time.
The therapeutic responses to infliximab and adalimumab tend to fade over time, but the majority of patients still do well after 1-3 years of continuous therapy, said Dr. Gordon. His analysis of the phase III REVEAL trial extension showed that 83% of patients with at least a PASI-75 response through the first 33 weeks of adalimumab therapy continued to have a PASI-75 or better response through 100 weeks, and 76% of the original responders were still in that category after 160 weeks of therapy (J. Am. Acad. Dermatol. 2012;66:241-51).
The data on the long-term safety of antitumor necrosis factor agents are extensive and largely reassuring, Dr. Gordon noted.
"I make the argument that there is more known about anti-TNF therapy in terms of safety than any other medicines ever," Dr. Gordon said. Much of the data come courtesy of Europe, where most patients are able to get on anti-TNF therapy only if a physician enrolls them in a registry, he added.
The primary safety risk posed by biologic therapy is serious infections, in Dr. Gordon’s opinion. The collective registry experience in rheumatoid arthritis patients suggests that risk is about 20% greater than in patients on methotrexate, and this risk appears to be stable over time. But it’s probably a mistake to extrapolate from the rheumatologic experience to psoriasis, Dr. Gordon said. He and his colleagues have shown that rheumatoid arthritis patients on biologic therapy tend to be older and more likely to be on concomitant systemic corticosteroids and other immunosuppressive drugs than are psoriasis patients (Ann. Rheum. Dis. 2009;68:1863-9). More data on the risks of biologic therapies in psoriasis patients are anticipated from PSOLAR and other large ongoing patient registries, he said.