GOTHENBURG, SWEDEN – In patients with both plaque psoriasis and psoriatic arthritis, initial treatment with etanercept at 50 mg twice weekly resulted in faster clearance of skin lesions than 50 mg once weekly.
The twice-weekly regimen, however, offered no advantage for treatment of joint and tendon symptoms. These were the key findings of the Psoriasis Randomized Etanercept Study in Subjects with Psoriatic Arthritis (PRESTA), a collaborative study that paired dermatologists and rheumatologists in an effort to determine how to optimize the use of etanercept to treat both skin and rheumatologic symptoms in these dual-diagnosis patients.
The PRESTA results will enable physicians to individualize treatment of such patients with a degree of confidence not before possible, Dr. Wolfram Sterry, one of the study investigators, said at the annual congress of the European Academy of Dermatology and Venereology.
PRESTA findings suggest that patients with more severe cutaneous disease are best off with an initial 12 weeks of etanercept (Enbrel) at 50 mg twice weekly before stepping down to 50 mg once weekly, while 50 mg/week from the outset is sufficient in patients with milder skin involvement, explained Dr. Sterry, professor and chair of the department of dermatology and allergy at Charit? University Hospital, Berlin.
PRESTA also showed the ideal dosing regimen for psoriatic arthritis to be closer to that employed in rheumatoid arthritis than for that used in psoriasis, he added.
PRESTA was a 24-week, multicenter, randomized, double-blind clinical trial in 752 patients with both psoriasis evaluated by dermatologists and psoriatic arthritis evaluated by rheumatologists. Participants were assigned to subcutaneous etanercept at either 50 mg once or twice weekly for 12 weeks, after which everyone received open-label etanercept at 50 mg/week for a further 12 weeks.
The primary efficacy end point was the number of patients achieving “clear” or “almost clear” on the Physician’s Global Assessment of psoriasis at 12 weeks. This outcome was obtained in 46% (176 of 379) of patients on twice-weekly therapy, compared with 32% (119 of 373) of patients on once-weekly treatment, a significant difference, said Dr. Sterry. In addition, the twice-weekly etanercept group showed significantly greater improvement from baseline to week 12 in the Psoriasis Area and Severity Index: 71%, compared with 62% for once-weekly therapy.
In contrast, both groups were equally likely to meet American College of Rheumatology (ACR) criteria for treatment response. At week 12, an ACR 20% response was achieved by 66% of patients on twice-weekly and 61% on once-weekly etanercept. An ACR 50% response was documented in 45% of those on twice-weekly and 41% on once-weekly etanercept. An ACR 70% response occurred in 20% on twice-weekly and 22% on once-weekly therapy, he noted.
By week 24, 66% of patients who initially got twice-weekly etanercept had an ACR 20% response and 35% had an ACR 70% response, as did 61% and 37%, respectively, of patients on 50 mg once weekly for the full 24 weeks.
Of note, by 24 weeks both patient groups achieved comparable improvements in their skin disease. Patients who initially received twice-weekly etanercept had a 78% improvement from baseline in the psoriasis area and severity index, while those on once-weekly therapy all along had a 74% improvement.
Another noteworthy finding, said Dr. Sterry, is that the study showed definitively, for the first time, that etanercept significantly improves two clinically important extra-articular manifestations of psoriatic arthritis: dactylitis and enthesis. These disease manifestations were present at baseline in 42% and 38% of patients, respectively. By week 24, dactylitis scores had improved by a mean of 85%, compared with baseline in both study arms, while enthesis scores improved by 81%.
There were no significant differences in the safety profiles between the two study arms.
The prevalence of psoriatic arthritis among psoriasis patients is estimated to be up to 30%, noted Dr. Sterry. The arthritis component typically does not present until about a decade after onset of the skin disease. This was true in PRESTA: Participants had a mean 18.9-year duration of psoriasis, with psoriatic arthritis appearing 11.9 years after the skin disease.
Dr. Sterry disclosed that he has received consulting fees from Wyeth, which sponsored PRESTA, as well as from Abbott, Schering-Plough, and Janssen-Cilag.