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Role of biologics: ustekinumab


and PHOENIX 2, were also performed to evaluate the clinical efficacy of ustekinumab for the treatment of moderate-to-severe psoriasis.1,22,23


Each


study had three phases: a 12-week placebo-controlled phase, a 28- or 40-week placebo crossover phase, and finally a randomised maintenance/ withdrawal phase (weeks 40–76) in PHOENIX 1, and a randomised dose intensification phase (weeks 28–52) in PHOENIX 2.1,22–24


Therefore, while


PHOENIX 1 study included a maintenance/withdrawal phase following active treatment, PHOENIX 2 assessed the effects of dose intensification in patients who responded only partially to ustekinumab.25


In the PHOENIX 1 trial,


patients who were initially randomised to receive ustekinumab at week 0 and achieved long-term response (PASI 75 at weeks 28 and 40) were re-randomised at week 40 to maintenance ustekinumab or withdrawal from treatment until loss of response. After week 76, subjects continued on treatment in a long-term extension for up to five years. In the PHOENIX 1 trial, which included 766 patients, 67.1% and 66.4% of patients in the ustekinumab groups (45mg and 90mg, respectively) reached the primary endpoint (PASI 75) at week 12, versus 3.1% of the patients in the placebo arm (p<0.0001).22


Maintenance


treatment with ustekinumab for up to five years of follow-up resulted in consistent, significant clinical response in adults with moderate-to-severe plaque psoriasis.25 In PHOENIX 2, where 1230 patients were randomised, similar results were observed, with 66.7% and 75.7% of PASI-75 responders in the ustekinumab 45mg and 90mg groups, respectively, compared with 3.7% in the placebo group (p<0.0001).23 12.7% of partial responders developed ustekinumab antibodies compared with 2% of the complete responders.23


Improvements in patient outcomes were seen as early as week 2 in PHOENIX 1 (as measured by Dermatology Life Quality Index) and PHOENIX 2 (as measured by PASI 50) in ustekinumab-treated patients. The maximum efficacy was observed between weeks 20 and 24.22,23 Improvements in PASI scores were sustained for up to three years: PASI 75 rates were 62% and 75% at week 76, and 64% and 76% at week 148 for patients receiving ustekinumab 45 and 90mg, respectively.26


The median time to loss of


response in patients who were withdrawn from treatment was about 15 weeks, but


80 60 40 20 0


0 4 8 12 16 20 24 28 Time (weeks) Figure 1: Proportions of patients in PSUMMIT1 trial achieving ACR20 responses. Adapted from Ref. 33. no rebounds were reported.23 Similar


response rates were achieved when treatment was restarted.22


Treatment with


ustekinumab 45 or 90mg also significantly improved health-related quality-of-life scores from baseline.27–29 While the results are better when receiving higher doses of ustekinumab (90mg), the response is not directly proportional to the dose. In the group of


ustekinumab treatment provided effective symptomatic improvement for almost half of the patients who showed no response to 12 weeks’ treatment with etanercept.32


Psoriatic arthritis


More recent data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis.


“More recent data indicate that ustekinumab also improves the symptoms of arthritis in patients with plaque psoriasis and psoriatic arthritis”


patients that achieved partial response, adjusting dose administration from every twelve weeks to every eight weeks significantly increased the therapeutic response in patients receiving 90mg.23 Predictive factors for partial response to ustekinumab were high body weight, long duration of psoriasis, previous inadequate response to more than one biological agent (35.5% versus 44.9%) and history of PsA (22.2% versus 34.8%). Adjusting ustekinumab dose to 90mg may result in a clinically meaningful improvement in response in patients ≤100kg with suboptimal initial response (please note that a 90mg dose is only recommended in patients with a body weight >100kg).30 Besides, following 12 weeks’ treatment, ustekinumab 45 or 90mg was superior to etanercept 50mg twice weekly in the treatment of moderate-to-severe psoriasis in another Phase III trial (ACCEPT), where ustekinumab and etanercept were compared head-to-head: 67.5% and 73.8% of patients receiving ustekinumab 45mg or 90mg, compared with 56.8% of patients with etanercept (p=0.01 and p<0.001, respectively), as evaluated by PASI 75 over a 12-week period.31


Furthermore,


Ustekinumab has been evaluated in psoriatic arthritis in the PSUMMIT133 PSUMMIT234


and studies. In these two large


randomised, placebo-controlled Phase III trials, 615 patients (in PSUMMIT1) and 312 patients (in PSUMMIT2) were randomised to receive ustekinumab (45 or 90mg SC) at weeks 0 and 4, and every 12 weeks, or a placebo. Patients were required to have active disease despite traditional treatments in PSUMMIT1, and despite traditional treatments or anti-TNF-a agents in PSUMMIT2. The primary endpoint for the PSUMMIT1 and PSUMMIT2 studies was the rate of ACR20 responders at week 24. The results showed a higher proportion of responders in the ustekinumab arms in both studies compared with placebo: 42.4% in patients receiving ustekinumab 45mg versus 49.5% in the 90mg group versus 22.8% in the placebo group (p<0.001) in PSUMMIT1 trial; and 43.7% versus 43.8% versus 20.2% (p<0.001) in ustekinumab 45mg, 90mg and placebo, respectively, in PSUMMIT2.33,34 The highest ACR20 response rates were at week 28, and they were maintained at week 52 (55.7% in patients


www.hospitalpharmacyeurope.com 32 36


Placebo (n=206) Ustekinumab 45mg (n=205) Ustekinumab 90mg (n=204)


40 44 48 52


15


Patients (%)


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