Psoriasis Responds to Intermittent Etanercept
KOHALA COAST, HAWAII — New data suggest that etanercept can be given intermittently like other psoriasis treatments, according to a poster that Alice B. Gottlieb, M.D., presented at a conference on clinical dermatology sponsored by the Center for Bio-Medical Communication Inc.
Data from the first study of intermittent or rotational use of etanercept came from a large phase III study in U.S. psoriasis patients. After the initial 24 weeks of the randomized, double-blind, controlled trial, 409 patients who responded with at least a 50% improvement in their Psoriasis Area Severity Index (PASI) scores stopped etanercept therapy.
Patients were followed monthly, and if their psoriasis relapsed (defined as losing at least half of the improvement seen in PASI while on treatment), they restarted etanercept at the dose originally assigned to them during the initial blinded phase of the study: weekly at 25 mg or twice-weekly at 25 or 50 mg.
At 60 weeks after all patients had started the original study, 46 remained in remission, 347 had relapsed and restarted etanercept therapy for psoriasis, and 16 patients withdrew from the study before reaching 60 weeks, she wrote.
The median time to relapse among the 498 patients was 85 days after the week-24 visit, when patients first discontinued etanercept. “After discontinuing etanercept, psoriasis gradually relapsed over approximately 3 months,” wrote Dr. Gottlieb of Robert Wood Johnson Medical School, New Brunswick, N.J.
Of the 347 patients who relapsed and restarted etanercept, 297 finished 12 weeks of retreatment. Improvements in PASI scores after retreatment were similar to improvements seen after initial treatment, she reported.
The study was funded in part by the makers of etanercept, Immunex Corp., a wholly owned subsidiary of Amgen Inc. Dr. Gottlieb is a consultant and speaker for the company. An Amgen employee served as a coinvestigator in the study.
The percentages of patients who achieved at least a 75% improvement in PASI scores ranged from 14% to 49% after the first 12 weeks of treatment (depending on dosage group) and 19%-45% after 12 weeks of retreatment.
In the 297 patients who stopped and restarted etanercept, mean PASI scores were 19 at baseline, 6 after the initial 12 weeks of treatment and before disease relapse, and 6 after 12 weeks of retreatment.
About 33% of the 297 patients developed an adverse event during retreatment and 32% developed infection, rates that were similar to those seen in the initial treatment phase of the study.
Stopping etanercept was not associated with severe flares of disease or conversion of psoriasis morphology, and was generally well tolerated by patients, according to Dr. Gottlieb. Retreatment was not associated with an increase in antigenicity to etanercept or with formation of neutralizing antibodies to etanercept.
A subset analysis of 252 patients who achieved at least a 75% improvement in PASI scores after the first 24 weeks of treatment found that a median of 91 days passed between stopping therapy and disease relapse.
Only one patient had a relapse that met the National Psoriasis Foundation's definition of rebound—a PASI score that's 125% or greater of baseline within 3 months of stopping therapy.
Etanercept is a fully human soluble tumor necrosis factor receptor that has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis.
Many psoriasis drugs are used intermittently or in a rotating manner because they lose their effectiveness over time or cause cumulative, dose-dependent toxicity. Etanercept does not appear to produce cumulative toxicity with chronic, continuous treatment of rheumatoid arthritis, according to Dr. Gottlieb.
