LAS VEGAS – Most patients taking etanercept or adalimumab for psoriasis can interrupt therapy and restart when needed, but not all of them will get as good a response the second time around.
With either biologic agent, response rates are slightly higher in patients on continuous therapy than in patients who stop and restart therapy, separate speakers said at a dermatology seminar sponsored by Skin Disease Education Foundation (SDEF).
But for a patient who plans to travel and doesn’t want to take along a case of syringes for etanercept injections, a physician can advise that the psoriasis probably won’t return for a few months after stopping the drug, and that restarting etanercept probably will produce a fairly good response, said Dr. Francisco A. Kerdel, director of the dermatology inpatient service at University of Miami Hospital.
Phase III trials of both drugs included arms that allowed withdrawal from therapy and the possibility of retreatment. "This is what happens in real life," he said. "Patients lose their insurance, or they don’t take their medicine, or they have some kind of surgery. Surgeons won’t operate unless the patients discontinue the drug."
On any dosage of etanercept, patients who discontinued the drug lost about half of the improvement they had gained on therapy at approximately 3 months after stopping treatment.
"Do patients flare faster than this in real life? Yes, but in the studies at least we have some data to suggest that it takes a while for patients’ psoriasis to come back," Dr. Kerdel said. Patients who restarted treatment and again discontinued etanercept had similar responses.
A separate randomized, open-label study comparing continuous versus interrupted etanercept therapy in more than 2,500 psoriasis patients showed there was a better response rate after 24 weeks in the continuous-treatment group (71%) than with interrupted therapy (60%), he said (J. Am. Acad. Dermatol. 2007;56:598-603).
"While you can stop and restart, it’s probably not a good idea," Dr. Kerdel said. "I don’t think you should treat psoriasis like you do a light switch and turn it on and off."
Several long-term safety studies that have followed hundreds of patients out to 3 years suggest that continuous etanercept remains efficacious and there is no cumulative toxicity.
Three-year data on adalimumab also suggest that response rates stabilize over time and that no new toxicities emerge, but for both biologic drugs these may be factors of patient selection, Dr. Kenneth B. Gordon said in a separate presentation.
"I would argue that with every medication there is some lost effect over time," said Dr. Gordon of the University of Chicago. Response rates are more variable initially but tend to stabilize over time, because the patients who stay on treatment tend to be the ones who are doing well on it. "You develop a high responding population that’s going to be able to maintain that response over time," he said.
This means, though, that you can tell patients that "if you get them through the first year, the likelihood is that the drug is going to keep on working," Dr. Gordon said.
An unpublished subanalysis by other investigators of phase III trial data on adalimumab looked at patients with a 75% improvement in Psoriasis Area and Severity Index (PASI 75) score after 33 weeks of adalimumab therapy. Among 227 patients who stopped and restarted adalimumab, retreatment recaptured the therapeutic effects, but never quite to the levels seen in 233 patients on continuous treatment. At week 108, 73% on retreatment and 75% on continuous treatment had a PASI 75.
"It’s important to tell patients that when you stop medication, you can restart and there’s a real good chance that you will recapture response, but it’s not in 100% of patients," Dr. Gordon said.
A separate subanalysis of the same data suggests that patients whose psoriasis returns most vigorously after stopping adalimumab are the least likely to recapture their previous response to treatment fully after restarting the drug. Among 70 whose PASI scores fell below 60 before restarting adalimumab, 58% had a PASI 75 at week 108. In 55 patients with a PASI score of 60-74 when restarting adalimumab, 81% achieved a PASI 75 at week 108. In 102 patients with a PASI score of 75-100 when restarting the drug, 86% had a PASI 75 at week 108, he said.
SDEF and this news organization are owned by Elsevier. Dr. Kerdel and Dr. Gordon have been speakers or consultants for, or have received grants from, Amgen (which markets etanercept), Abbott (which markets adalimumab), Centocor, and Merck. Dr. Kerdel also has had associations with Eisai, Astellas, Genentech, Stiefel, Novartis, and Wyeth. Dr. Gordon has had associations with Lilly, Pfizer, Celgene, and Medicis.