SAN ANTONIO — Long-term, continuous use of ustekinumab for maintenance therapy in patients with moderate to severe plaque psoriasis is efficacious and generally well tolerated, according to phase III study findings reported at the annual meeting of the American Academy of Dermatology.
The results of the PHOENIX I trial, a randomized, double-blind, placebo-controlled crossover trial of the novel human monoclonal antibody against interleukins 12 and 23, showed treatment response was better maintained at 76 weeks in responders who received 45 mg or 90 mg of ustekinumab every 12 weeks, compared with those who stopped treatment at 40 weeks, Dr. Kenneth B. Gordon of Northwestern University, Chicago, said in a poster session.
The drug's maker (Centocor Inc.) announced last month that its Biologics License Application for ustekinumab (CNTO 1275) had been accepted for review by the Food and Drug Administration.
The results of another phase III study of the drug (PHOENIX II), reported in October at the World Congress of Dermatology in Buenos Aires, showed ustekinumab was effective and safe in more than two-thirds of 1,230 patients with moderate to severe disease who received two subcutaneous doses of the drug. A 75% improvement in the psoriasis severity area index score (PASI 75) was achieved in 67% of patients randomized to receive 45-mg doses, 76% of those randomized to receive 90-mg doses, and 4% of those in the placebo group.
For the current study, 766 patients were randomized to receive placebo or 45 mg or 90 mg of subcutaneous ustekinumab at weeks 0 and 4 of the study, and then every 12 weeks thereafter. At the 12-week mark, those in the placebo group crossed over to receive 45 mg or 90 mg of ustekinumab then and at week 16 and then every 12 weeks thereafter.
At 40 weeks, the 160 patients in the 45-mg treatment group from baseline and the 161 in the 90-mg treatment group from baseline who achieved a PASI 75 response at weeks 28 and 40 were further randomized to ongoing treatment or placebo every 12 weeks.
Of those in the ongoing treatment groups, 96% maintained at least a PASI 50 score through week 76, compared with just over 30% in the placebo groups; PASI 75 and 90 scores were also maintained in more patients in the ongoing treatment groups, compared with the placebo groups (see chart). At 40 weeks, about 75% of the 90-mg group had disease rated as cleared or minimal on the Physician's Global Assessment.
Maintenance therapy with ustekinumab was well tolerated in this study at both the 45-mg and 90-mg doses, and safety was “generally comparable” with that with interrupted therapy after 40 weeks in both groups, noted Dr. Gordon, who received research support for the study from Centocor. No cases of tuberculosis, anaphylactic or serum sickness-like reactions, or injection-site reactions occurred. The most common adverse events were upper respiratory tract infection, nasopharyngitis, arthralgia, and headache (see chart).
Patients in PHOENIX I were at least 18 years old, had been diagnosed with plaque psoriasis for at least 6 months (most had a disease duration of about 20 years), had a baseline PASI score of 12 or higher, and had at least 10% body surface area involvement. Those with nonplaque forms of psoriasis, with a recent serious systemic or chronic infection, a history of tuberculosis, or a known malignancy were excluded. Baseline disease characteristics were similar across the groups, with 23%–25% body surface area involvement and baseline PASI scores of 19–20 in all groups.
Baseline Dermatology Life Quality Index (DLQI) scores were 11 or 12 in all groups and improved markedly when the PASI 75 primary end point was reached. But in those switched from treatment to placebo in the randomized withdrawal phase, DLQI scores returned to baseline even in those whose PASI scores were above baseline. “This means when people get better, they don't want to get worse again,” Dr. Gordon said in an interview. “Even with clinical improvement … they are no longer tolerant of the amount of psoriasis they once had.”
The findings show that the drug might “control plaque psoriasis with as few as four injections a year,” he noted in a press statement. The drug targets different proteins involved in the inflammatory process and development of psoriasis. “The molecule attacks, binds to, and inactivates interleukin 12 and 23. The latter is important in activating the immune process and impacting the keratinocyte response, which are seen as the clinical manifestations of psoriasis.
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