MADRID, Spain — Open-label results from a phase 3 study assessing ustekinumab (Stelara, Janssen) show that the improvement achieved at week 24 is confirmed at week 52 in patients with psoriatic arthritis.
The results of the trial known as PSUMMIT II showed sustained improvement in patients previously treated with antitumor necrosis factor inhibitors as well as those not treated.
"Although the development of anti-TNF treatments has drastically improved the treatment of psoriatic arthritis, substantial numbers of patients fail to respond to therapy," said lead investigator Christopher Ritchlin, MD, from the University of Rochester Medical Center, in New York.
"We have not had good alternative therapies for patients who have to stop anti-TNF treatment," he said. "Now an alternative drug has demonstrated improvements not just in anti-TNF-naïve patients, but also in those who have been treated with one or more anti-TNF agent so we consider this an advance."
Dr. Ritchlin presented the results here at the European League Against Rheumatism (EULAR) Congress 2013.
Ustekinumab is an interleukin-12 and interleukin-23 antagonist, approved in the United States for treating moderate-to-severe psoriatic plaques in adults. The manufacturer, Janssen, has filed for approval in the US for treatment of active psoriatic arthritis.
This study included 312 patients randomized to 1 of 3 arms — placebo, ustekinumab 45 mg/day, and ustekinumab 90 mg/day. Of these patients, 180 were previously exposed to 1 to 5 anti-TNF agents.
Patients were treated with ustekinumab at weeks 0, 4, and 16, followed by every 12 weeks up to week 40. Or with placebo at weeks 0, 4, and 16, followed by crossover to ustekinumab 45 mg for week 24, week 28, and week 40.
At baseline, all patients had elevated C-reactive protein from 11 to 20 swollen and tender joints and a history of active plaque psoriasis. Patients with latent tuberculosis were allowed to enroll in the trial.
As previously reported by Medscape Medical News , at week 24 significantly more patients treated with ustekinumab achieved the primary endpoint of at least a 20% response according to American College of Rheumatology criteria compared with placebo (P < .001 for all comparisons with placebo).
The new data show that the ACR20 response was sustained at week 52. Ustekinumab reduced the signs and symptoms of psoriatic arthritis by at least 20% and up to 70% in some patients, and improved physical function, plaque psoriasis, dactylitis, and enthesitis.
Table. ACR20 at Week 24 and Week 52
|Treatment||Week 24 (%)||Week 52 (%)|
|Ustekinumab 45 mg||43.7||46.8|
|Ustekinumab 90 mg||43.8||48.4|
Safety was similar in the ustekinumab and placebo arms of the study, Dr. Ritchlin reported. Ustekinumab was well tolerated with no deaths, tuberculosis, or opportunistic infections reported through 60 weeks of the study.
"These new data show that patients with psoriasis can have comfort in the knowledge that there is an effect of this drug on the joint," he said.
Patients previously treated with an anti-TNF inhibitor had more active disease at baseline compared with the treatment-naïve patients. More robust responses were seen in those who were anti-TNF-naïve compared with those previously treated. The range of ACR20 was 59% to 73% in the untreated patients compared with 37% to 41% in those who had taken other options.
The response rate was lower in those previously treated with 3 or more anti-TNF agents (13% to 30%) compared with 1 or 2 agents (13% to 55%).
At week 52 in the overall population, at least a 50% improvement in signs and symptoms of psoriatic arthritis was seen in 29% of the placebo group assigned to 45 mg of ustekinumab, 28% for ustekinumb 45 mg, and 26% for ustekinumab 90 mg.
ACR70 response rates were 16%, 12%, and 18%, respectively. The Psoriasis Area and Severity Index 75 (PASI 75), which is a high bar for skin improvement, was achieved by 56%, 57%, and 84%.
"Although those previously exposed to agents did not have as robust a response on ACR20/50/70 as those not exposed, the range was still better than placebo," Dr. Ritchlin said.
"The challenge with ustekinumab is the effect on joints," Ulf Müller-Ladner, MD, from the University Giessen, in Germany, told Medscape Medical News. "The drug has a good safety profile. The data today suggest that the effect on joints may meet the challenge, but the data were not overwhelming in this regard. We will have to see how the drug behaves in real-world patients."
This study was funded by Janssen. Dr. Ritchlin disclosed grant and research support from the company, and 4 of the 9 coauthors of the study are Janssen employees and shareholders of Johnson & Johnson, the parent company of Janssen. Dr. Müller-Ladner said he has received consultant and research grants from every company that makes biologics for the treatment of rheumatic diseases.
European League Against Rheumatism (EULAR) Congress 2013: Abstract OP0001. Presented June 12, 2013.
Medscape Medical News © 2013 WebMD, LLC
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Cite this: Ustekinumab Efficacy Sustained for Psoriatic Arthritis - Medscape - Jun 12, 2013.