Analyses of data from two large, prospective, phase 3 studies investigating ustekinumab (Stelara, Janssen Biotech) for the treatment of moderate-to-severe plaque psoriasis are consistent in demonstrating the safety and efficacy of restarting the biologic if treatment is temporarily interrupted.
New York - Analyses of data from two large, prospective, phase 3 studies investigating ustekinumab (Stelara, Janssen Biotech) for the treatment of moderate-to-severe plaque psoriasis are consistent in demonstrating the safety and efficacy of restarting the biologic if treatment is temporarily interrupted.
The findings from post-hoc analyses investigating responses to retreatment with ustekinumab were presented in a poster at the 2011 summer meeting of the American Academy of Dermatology. They showed that among patients who initially responded to ustekinumab; withdrew from therapy; and then reinitiated treatment because of relapse, about 85 percent or more recaptured the treatment benefit.
Dr. Lebwohl says the positive efficacy and safety profile of reinitiated ustekinumab contrasts with outcomes of restarting treatment with other biologics. For example, responders to infliximab (Remicade, Janssen Biotech) who stop treatment are likely to develop antibodies to the biologic agent that mitigate future therapeutic response, and they also are at increased risk for developing an infusion reaction.
"Analyses of responses in patients restarting ustekinumab identified negative status for antibodies to the biologic as a potential predictor of response. However, antibody development occurs much less frequently in patients treated with ustekinumab compared with infliximab," Dr. Lebwohl says.
The retreatment analyses were based on data from the phase 3, placebo-controlled PHOENIX 1 study and the ACCEPT clinical trial that compared ustekinumab with etanercept (Enbrel, Amgen/Pfizer). The inclusion criteria for ACCEPT required patients to be naïve to etanercept and to have failed, be intolerant to, or have a contraindication to at least one conventional systemic agent. Both studies evaluated ustekinumab doses of 45 mg and 90 mg administered initially at weeks 0 and 4.
In PHOENIX 1, treatment was continued at weeks 12 and 28. Patients achieving a Psoriasis Area and Severity index (PASI)-75 response at week 40 were rerandomized to placebo or continued ustekinumab, and ustekinumab could be restarted if the patient lost at least 50 percent of the improvement gained from baseline. A total of 297 patients restarted ustekinumab and 260 patients were evaluated after 12 weeks.
In ACCEPT, treatment was withheld beginning at week 12 from patients who achieved a physician's global assessment (PGA) score less than or equal to 2 (mild, minimal, clear) and could be restarted if the PGA worsened to greater than or equal to 3. A total of 494 ustekinumab patients had treatment discontinued at week 12, 399 patients restarted therapy and 375 patients were evaluated after 12 weeks.
For both studies and across both dose groups, 84 to 89 percent of patients who restarted ustekinumab regained treatment response (PASI-75 for PHOENIX 1 and PGA less than or equal to 2 for ACCEPT) after 12 weeks; median PASI improvement from baseline for the two dose groups in the two studies ranged from 85 to 90 percent.
Efficacy of retreatment with ustekinumab was also analyzed for the smaller subgroups of patients in PHOENIX 1 and ACCEPT who were "partial responders" to initial treatment, defined as achieving a PASI response between 50 and 75. The majority of these patients reachieved a PASI response of 65 of better at 12 weeks after restarting ustekinumab, and the median percent PASI improvement from baseline was about 65 percent.