Each drug delivers a different level of efficacy and duration and, therefore, requires a different treatment strategy to optimize its impact.
New York - Long-term studies are beginning to yield encouraging news about leading biologic drugs' effectiveness against psoriasis.
Each drug, however, delivers a different level of efficacy and duration and, therefore, requires a different treatment strategy to optimize its impact.
"We know that alefacept (Amevive, Biogen) has an extremely long-lived effect in patients," says Craig L. Leonardi, M.D., associate clinical professor of dermatology, St. Louis University, Missouri. "Its primary mode of action is to deplete the pool of memory-effector T-cells. And, in fact, after 12 weeks of dosing, those T-cell levels are depressed for many months after the last dose."
"The issue with this drug is, who's going to have that response? That's the part that's very tough - there's no predictor of response right now," Dr. Leonardi says. "With alefacept, overall, the response is the slowest of the biologic drugs we have. The maximum response can be seen well after the last dose. In some patients, it's a very long-lived response, from six to seven months."
RaptivaConversely, Raptiva (efalizumab, Genentech), approved by the U.S. Food and Drug Administration last October, requires continuous dosing because of its shorter action profile. Its maker recently concluded a three-year trial, which represents the longest-running biologic drug trial to date. At press time, researchers had analyzed data through 30 months.
"The news here is very good," Dr. Leonardi says.
In an intent-to-treat population, the as-yet-unpublished data show that at 30 months, 50 percent of patients achieved a 75 percent reduction in Psoriasis Area and Severity Index (PASI) scores. And, in fact, 29 percent had achieved 90 percent reductions.
"This just shows the utility of this drug over a long period of time," Dr. Leonardi explains. "These are very significant numbers. They show that in a chronic-dosing setting, this drug maintains efficacy. And there might be a suggestion that the PASI 90 population increases over time. I don't know if it's statistically significant, but there's a trend upwards. The good news is that a lot of patients are very happy with continuous dosing on this medicine."
EnbrelLike Raptiva, Enbrel (etanercept, Amgen/Wyeth) is a fairly short-acting drug.
"When you discontinue etanercept," Dr. Leonardi says, "the psoriasis does recur. It takes about 12 weeks for it to come halfway back. So that's a little bit longer than Raptiva, which has a relapse time of nine or 10 weeks. But there's no significant difference between these two drugs in that regard because they're both used chronically, not intermittently."
As yet, there have been no long-term studies of etanercept. The longest trial lasted 24 weeks. It shows that at this interval with standard doses, 44 percent of patients achieved PASI 75, and at high doses (50 mg twice weekly) 59 percent achieved PASI 75 (N Engl J Med. 2003 Nov 20;349(21):2014-2022).
RemicadeThe IV infusion drug Remicade (infliximab, Centocor), on the other hand, achieved very rapid onset of response in a recent phase 2 B study.
"This drug works faster than any other (biologic) drug out there," says Dr. Leonardi. "It offers the best efficacy and has a very long-lived response."