SONOMA, CALIF.– Data support dosage escalation or intensification for patients who don’t respond to biologic therapy for psoriasis, but only for three of the four biologic agents available in the United States, Dr. April W. Armstrong said at the annual Coastal Dermatology Symposium.
It may make sense to increase the dose or shorten the intervals between doses in some patients with psoriasis who don’t respond to etanercept, adalimumab, or ustekinumab, she suggested.
Dr. April W. Armstrong
For infliximab, however, increasing the standard 5-mg/kg dose to 10 mg/kg in nonresponders did not significantly improve efficacy in one randomized study of patients with moderate to severe psoriasis. Consider combination therapy instead of dose escalation in those patients, said Dr. Armstrong, director of the psoriasis program at the University of Colorado, Denver.
Most clinical trials of dose escalation for psoriasis target patients in whom conventional doses produce only a partial response, defined as a Psoriasis Area and Severity Index (PASI) score of 50-75, or no response, defined as a PASI score below 50, she said.
A conventional dosage of etanercept for psoriasis uses 50 mg twice weekly for 12 weeks, followed by 50 mg once weekly for maintenance, Dr. Armstrong said. In an open-label extension of a study of 912 patients with moderate to severe psoriasis who received 12 weeks of etanercept therapy, nonresponders who escalated the maintenance dosage to 50 mg twice weekly boosted the likelihood of achieving a PASI 75 from 33% at 12 weeks to 44% at 48 weeks and 43% at 72 weeks (J. Drugs Dermatol. 2010;9:928-37).
Safety profiles were similar between standard dosing and escalated or intensified dosing in studies of all four biologic therapies, Dr. Armstrong said at the symposium, jointly presented by the University of Louisville (Ky.) and the Global Academy for Medical Education.
In the etanercept study, rates of serious infections were 0.9 events per 100 patient-years on standard maintenance therapy and 1.9 events per 100 patient-years on the escalated dosage. Myocardial infarctions occurred in none of 321 patients on standard maintenance therapy and in 2 of 591 patients on the twice-weekly dosage.
The conventional dosage of adalimumab for psoriasis is 80 mg at the start of therapy, followed by 40 mg every other week starting at week 1. In an open-label extension of a study of 147 patients, those who did not achieve a PASI 50 by week 25 were allowed to escalate the maintenance therapy dosage to 40 mg weekly. By week 60, 64% of patients in the dose-escalation group achieved a PASI 75, compared with 56% of patients who had been on the standard regimen and 45% of patients who had started with placebo for 12 weeks and then went on the standard dosage (J. Am. Acad. Dermatol. 2006;55:598-606). The mean PASI score improved by 27% after 8 weeks on the escalated dose, Dr. Armstrong said.
Three malignancies and two cardiovascular events (one leading to death) developed in the escalated-dosage group, compared with two malignancies and a serious case of coccidiomycosis in the standard-therapy group, she noted.
The conventional dosage for ustekinumab is 45 mg in patients weighing up to 100 kg or 90 mg in heavier patients, administered in subcutaneous injections at weeks 0 and 4, then every 12 weeks thereafter. In the only head-to-head study comparing biologic therapies for psoriasis, ustekinumab was more effective than etanercept in the first 3 months, Dr. Armstrong noted. The 12-week Active Comparator (CNTO1275/Enbrel) Psoriasis Trial (ACCEPT) found that 74% of 347 patients on 90 mg of ustekinumab and 68% of 209 patients on 45 mg of ustekinumab achieved a PASI 75, compared with 57% of 347 patients on etanercept (N. Engl. J. Med. 2010;362:118-28).
In a separate study of 158 patients with psoriasis who only partially responded to standard ustekinumab therapy after 24 weeks, maintenance dose escalation to every 8 weeks instead of 12 significantly improved response rates in patients on 90 mg but not in those on 45 mg. By week 52, 69% of patients receiving 90 mg ustekinumab every 8 weeks achieved a PASI 75, compared with 33% of patients on ustekinumab 90 mg every 12 weeks (Lancet 2008;371:1675-84). In the patients on 45 mg ustekinumab, the proportions achieving PASI 75 by week 52 did not differ significantly between those receiving the drug every 8 or 12 weeks.
One cutaneous malignancy, one noncutaneous malignancy, and two other serious adverse events occurred in the intensified-therapy groups, compared with one serious infection and two other serious adverse events in the standard-therapy groups.
The conventional dosage of infliximab for psoriasis is 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks. A study that randomized 33 patients with moderate to severe psoriasis to 10 weeks of therapy with placebo or 5 mg/kg or 10 mg/kg of infliximab at weeks 0, 2, and 6 found that 91% of patients on the escalated dose and 82% on the standard dose of infliximab achieved a Physician Global Assessment score of good, excellent, or clear, compared with 18% of patients on placebo (Lancet 2001;357:1842-7).