August 8, 2011 (New York, NY) — Ongoing studies of the novel interleukin (IL)12/23 monoclonal antibody ustekinumab (Stelara; Janssen Biotech, Inc [formerly Centocor]; Horsham, Pennsylvania) continue to show sustained efficacy and a high benefit-to-risk ratio, with a number needed to treat (NNT) of less than 2. Results were reported here at the American Academy of Dermatology (AAD) Summer Academy Meeting.
Ustekinumab has been approved for the treatment of moderate to severe psoriasis. The AAD included this drug in its treatment guidelines, published in the February issue of the Journal of the American Academy of Dermatology, for the treatment of moderate to severe psoriasis. At the AAD Annual Meeting, also in February, new study findings showed that the drug achieves a high resolution of symptoms but does not affect the underlying disease process.
At the Summer Academy Meeting, many studies have continued to evaluate the safety and efficacy of ustekinumab.
Kenneth B. Gordon, MD, head of dermatology at NorthShore University Health System in Skokie, Illinois, and colleagues reported in their study abstract that "the majority of responders [in PHOENIX 1 and the ACCEPT trial] withdrawn from ustekinumab treatment were able to recapture clinical response after 12 weeks of retreatment."
Retreatment resulted in 84% to 85% of patients achieving a Psoriasis Area and Severity Index (PASI) 75 at week 12 in PHOENIX 1, and "85-89% of retreated patients in ACCEPT re-achieved a PGA [Physician's Global Assessment] ≤ 2 (clear/minimal/mild) response at week 12."
Predictors of response were a lower baseline body weight and no antibodies against ustekinumab. The researchers found "no safety concerns with treatment."
Tsen-Fang Tsai, MD, from the Department of Dermatology, National Taiwan University Hospital in Taipei, and colleagues in Germany, the United States, and Canada, report that the drug shows similar efficacy in Asian and non-Asian populations with moderate to severe psoriasis.
They compared results of PHOENIX 1 and PHOENIX 2, involving nearly 2000 North American and European patients, with those of JPN-02 and PEARL, involving nearly 300 Japanese, Korean, and Taiwanese patients. All but PEARL evaluated results of ustekinumab 45 mg or 90 mg subcutaneously at week 0 and week 4 with placebo, with a third dose given at week 16. PEARL did not include the higher dose of the drug.
Efficacy was similar in both ethnic groups, and response was durable in both through week 28.
Silas Martin, MD, of Janssen Biotech, Inc, and colleagues conducted a benefit-risk analysis of the PHOENIX 1 and PHOENIX 2 trials. They reported in their abstract presented here at the AAD Summer Academy Meeting that "During the 12-week placebo-controlled period of the PHOENIX 1 and 2 trials, the risk difference for ustekinumab v. placebo for all efficacy measures was high, with corresponding low NNT values."
Improvement in PASI 75 was greater than 600 per 1000 patients for both 45-mg and 90-mg doses vs placebo. The NNT was less than 1.6. There were no significant risk differences between groups. The benefit-risk profile with ustekinumab was comparable to other biologics used to treat psoriasis.
One of the most important findings reported here, in the opinion of Mark Lebwohl, MD, chairman of the Department of Dermatology, Mt. Sinai School of Medicine in New York, NY, was that ustekinumab could be discontinued and then restarted with little loss of efficacy.
"If you stop and restart ustekinumab, you regain about 90% [of its effect]," he told Medscape Medical News. "This is new information."
Dr. Lebwohl said that it is possible to discontinue ustekinumab treatment without significant disease flare. "This may be due to the normal waxing and waning of psoriasis...but my inclination is to keep patients on it. It is a pretty safe drug and one of the most effective drugs we've ever had [for psoriasis] for long-term maintenance. It is dramatically effective."
"This is still a relatively new drug," Alan Menter, MD, chairman of the Department of Dermatology at Baylor College of Medicine in Dallas, Texas, and chairman of the AAD psoriasis treatment guidelines. "We only have about 5 or 10 years of data to draw from. However, ustekinumab is a welcome addition [to the treatment armamentarium]."
"We have three major categories of treatment — oral drugs, biologics, such as methotrexate and cyclosporin A, and drugs such as etanercept and ustekinumab. Methotrexate has a 2-year maximum duration of treatment, because of kidney toxicity and cyclosporin A can't be given to women of child-bearing age — but psoriasis is an equal opportunity disease." The IL blockers are an important addition to treatment options, he said.
"All of these have sight differences in efficacy, and some patients fail to respond to respond to one or more of these," Dr. Menter observed. "This is still a drug used as second-line therapy, but ustekinumab is good for patients who are [tumor necrosis factor]–alpha-resistant, and it can be combined with other therapies.
However, clinical trial use is different than clinical use," Dr. Menter cautioned, "and there have been no head-to-head studies. "Patient populations in clinical trials are carefully restricted, which is not the case in clinical practice." As such, treatment outcomes might not be the same.
He added that there are roughly 7 million people with psoriatic joint disease, of whom 1 million have moderate to severe disease. Of these, only approximately 200, 000 receive biologics. "This means that about 80% of people with psoriasis are undertreated."
Study authors Drs. Gordon, Tsai, and Martin have received funding from Centocor. Drs. Lebwohl and Menter have both served as consultants for Centocor, among most of the other makers of therapies for psoriasis, but neither has received any funding.
American Academy of Dermatology 69th Annual Meeting: Abstracts 2401, 2402, and 2403. Presented August 5, 2011.
Ustekinumab has been approved for the treatment of moderate to severe psoriasis. The AAD included this drug in its treatment guidelines, published in the February issue of the Journal of the American Academy of Dermatology, for the treatment of moderate to severe psoriasis. At the AAD Annual Meeting, also in February, new study findings showed that the drug achieves a high resolution of symptoms but does not affect the underlying disease process.
At the Summer Academy Meeting, many studies have continued to evaluate the safety and efficacy of ustekinumab.
Kenneth B. Gordon, MD, head of dermatology at NorthShore University Health System in Skokie, Illinois, and colleagues reported in their study abstract that "the majority of responders [in PHOENIX 1 and the ACCEPT trial] withdrawn from ustekinumab treatment were able to recapture clinical response after 12 weeks of retreatment."
Retreatment resulted in 84% to 85% of patients achieving a Psoriasis Area and Severity Index (PASI) 75 at week 12 in PHOENIX 1, and "85-89% of retreated patients in ACCEPT re-achieved a PGA [Physician's Global Assessment] ≤ 2 (clear/minimal/mild) response at week 12."
Predictors of response were a lower baseline body weight and no antibodies against ustekinumab. The researchers found "no safety concerns with treatment."
Tsen-Fang Tsai, MD, from the Department of Dermatology, National Taiwan University Hospital in Taipei, and colleagues in Germany, the United States, and Canada, report that the drug shows similar efficacy in Asian and non-Asian populations with moderate to severe psoriasis.
They compared results of PHOENIX 1 and PHOENIX 2, involving nearly 2000 North American and European patients, with those of JPN-02 and PEARL, involving nearly 300 Japanese, Korean, and Taiwanese patients. All but PEARL evaluated results of ustekinumab 45 mg or 90 mg subcutaneously at week 0 and week 4 with placebo, with a third dose given at week 16. PEARL did not include the higher dose of the drug.
Efficacy was similar in both ethnic groups, and response was durable in both through week 28.
Silas Martin, MD, of Janssen Biotech, Inc, and colleagues conducted a benefit-risk analysis of the PHOENIX 1 and PHOENIX 2 trials. They reported in their abstract presented here at the AAD Summer Academy Meeting that "During the 12-week placebo-controlled period of the PHOENIX 1 and 2 trials, the risk difference for ustekinumab v. placebo for all efficacy measures was high, with corresponding low NNT values."
Improvement in PASI 75 was greater than 600 per 1000 patients for both 45-mg and 90-mg doses vs placebo. The NNT was less than 1.6. There were no significant risk differences between groups. The benefit-risk profile with ustekinumab was comparable to other biologics used to treat psoriasis.
One of the most important findings reported here, in the opinion of Mark Lebwohl, MD, chairman of the Department of Dermatology, Mt. Sinai School of Medicine in New York, NY, was that ustekinumab could be discontinued and then restarted with little loss of efficacy.
"If you stop and restart ustekinumab, you regain about 90% [of its effect]," he told Medscape Medical News. "This is new information."
Dr. Lebwohl said that it is possible to discontinue ustekinumab treatment without significant disease flare. "This may be due to the normal waxing and waning of psoriasis...but my inclination is to keep patients on it. It is a pretty safe drug and one of the most effective drugs we've ever had [for psoriasis] for long-term maintenance. It is dramatically effective."
"This is still a relatively new drug," Alan Menter, MD, chairman of the Department of Dermatology at Baylor College of Medicine in Dallas, Texas, and chairman of the AAD psoriasis treatment guidelines. "We only have about 5 or 10 years of data to draw from. However, ustekinumab is a welcome addition [to the treatment armamentarium]."
"We have three major categories of treatment — oral drugs, biologics, such as methotrexate and cyclosporin A, and drugs such as etanercept and ustekinumab. Methotrexate has a 2-year maximum duration of treatment, because of kidney toxicity and cyclosporin A can't be given to women of child-bearing age — but psoriasis is an equal opportunity disease." The IL blockers are an important addition to treatment options, he said.
"All of these have sight differences in efficacy, and some patients fail to respond to respond to one or more of these," Dr. Menter observed. "This is still a drug used as second-line therapy, but ustekinumab is good for patients who are [tumor necrosis factor]–alpha-resistant, and it can be combined with other therapies.
However, clinical trial use is different than clinical use," Dr. Menter cautioned, "and there have been no head-to-head studies. "Patient populations in clinical trials are carefully restricted, which is not the case in clinical practice." As such, treatment outcomes might not be the same.
He added that there are roughly 7 million people with psoriatic joint disease, of whom 1 million have moderate to severe disease. Of these, only approximately 200, 000 receive biologics. "This means that about 80% of people with psoriasis are undertreated."
Study authors Drs. Gordon, Tsai, and Martin have received funding from Centocor. Drs. Lebwohl and Menter have both served as consultants for Centocor, among most of the other makers of therapies for psoriasis, but neither has received any funding.
American Academy of Dermatology 69th Annual Meeting: Abstracts 2401, 2402, and 2403. Presented August 5, 2011.
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