Friday May 16 2008
A 63 year old man with psoriasis. The skin appears white and flaky
Two trials of a new psoriasis treatment have given “hope” to sufferers, The Independent reported today. The newspaper said that the two separate studies show that a new drug – ustekinumab – is highly effective, has fewer side effects and is more convenient to take than existing treatments.
The research involved almost 2,000 patients with moderate to severe psoriasis and more than two–thirds of those treated had more than a 75% improvement in their skin’s condition.
Both studies were large, well conducted trials – funded by the manufacturers of ustekinumab – and both show that the drug significantly reduced the extent and severity of psoriasis compared to placebo. Longer term follow up – which is planned for both studies – will provide information on safety and effects beyond one year.
The current results will be taken into account when regulatory bodies discuss whether to license the drug later this year. The drug offers genuine hope for sufferers of this common, debilitating skin condition.
The expected cost of this treatment is not mentioned in the published studies or in the newspaper report. It is also unknown if the drug is effective in reducing symptoms from the arthritis caused by psoriasis. If it is licensed, both these factors will have an impact on how the drug is used and for whom it is recommended.
Where did the story come from?
There are two studies associated with the news article. The first was conducted by Dr Craig Leonardi, Dr Kenneth Gordon and investigators from the PHOENIX 1 study group, based across Canada and the USA. Institutions involved in the research include Saint Louis University Medical School, Harvard Medical School and the University of Western Ontario.
The second study was conducted by Kim Papp and investigators from the PHOENIX 2 study group, based across Canada, the USA and Germany. Institutions involved include the University of Western Ontario, Mount Sinai School of Medicine and Dermatologikum Hamburg in Germany. Both studies were funded by Centocor – the biotechnology company that manufactures the drug under study.
Both studies were published in the peer-reviewed medical journal: The Lancet.
What kind of scientific study was this?
The first study – PHOENIX 1 - was a randomised, double-blind, placebo-controlled trial. It assessed the effects of a new drug (ustekinumab) at treating moderate to severe psoriasis over a 12 week period. Psoriasis is a common skin condition appearing as red, scaly patches that can itch and cause pain.
The researchers enrolled 766 patients from 48 sites in the USA, Canada and Belgium. At the beginning of the study, they allocated equal numbers of the patients to one of three groups. A group that received 45mg of the drug, a group receiving double that amount (90mg) or a placebo group.
The patients in the ustekinumab groups were injected with the drug during the first week of the study, again at four weeks, and then every 12 weeks after that. The patients in the placebo group were given a dose of a placebo the first week and the fourth week of the study. After the first 12 weeks, the placebo group were also given the drug, and every 12th week after that.
The researchers also wanted to see if the treatment had to be given continually or if the drug’s effects are long lasting. They did this by randomly allocating the people who had had a very good response to the drug (75% improvement in severity) to either continuing or stopping treatment. The patients whose treatment was stopped were given it again once their psoriasis returned. This was done at both 28 and 40 weeks.
The second study – PHOENIX 2 – was also a randomised, double-blind, placebo-controlled trial that also enrolled people with moderate to severe psoriasis. The point of this study was to assess the effects and safety of the same drug – ustekinumab – after up to 52 weeks of treatment. The study also investigated if people who were “partial responders” after 28 weeks of treatment would respond to an increased dose of the drug. The researchers did this by randomly assigning partial responders to continuing to being given the injection every 12 weeks or to receiving treatment every eight weeks.
In this study, 1,230 patients from 70 sites across Austria, Canada, France, Switzerland, Germany, UK and the USA participated. Similarly to the first study, the patients were randomly assigned to being given different amounts of the drug or a placebo. After 52 weeks, the researchers were able to see how the response at 12 weeks was different between drug and placebo and how “partial responders” fared when their dose was increased or not.
The researchers measured the response to treatment using a recognised treatment score called PASI (the psoriasis area severity index). This score takes into account the extent of the disease, and looks at the severity of redness, scaling, and thickness in different body areas affected by psoriasis. The researchers counted the numbers of patients who achieved PASI 75 (i.e. they had improved by at least 75% compared to when they began the study.
What were the results of the study?
PHOENIX 1: More people achieved at least 75% improvement in severity after 12 weeks in both the ustekinumab groups than in the placebo group. The difference is substantial with 67% of the 45mg group, 66% of the 90mg group, and 3% of the placebo group reaching this goal.
The study also found that continuing treatment with the drug resulted in more people maintaining their improvement response after one year. If the drug was withdrawn at 40 weeks, it was more common for psoriasis symptoms to worsen. There were no differences between groups in the experience of side effects.
PHOENIX 2: This study had similar results to the first after 12 weeks. It found that both doses of ustekinumab resulted in more people achieving a response than placebo. The difference was again substantial with 67% of the 45mg group, 76% of the 90mg group, and 4% of the placebo group achieving at least 75% improvement in severity.
The patients who had only partially responded and so had their dose and frequency of dose changed were also found to have improved. Increasing their dose to 90mg every eight weeks improved response rate at one year compared to those continuing to receive treatment every 12 weeks. There were no differences in the groups in the experience of side effects.
What interpretations did the researchers draw from these results?
Overall, the conclusions from these studies are that ustekinumab is effective in treating moderate to severe psoriasis. It was found that most people who receive treatment every 12 weeks maintain the effects for at least a year.
Intensifying the dose to every eight weeks with 90mg of ustekinumab “might be necessary to elicit a full response in patients who only partially respond to the initial regimen”.
What does the NHS Knowledge Service make of this study?
These important and well-conducted studies could offer genuine hope for psoriasis sufferers. Both doses of the new drug – ustekinumab – performed significantly better than placebo with no notable difference in side effects.
As mentioned in an accompanying commentary to the two papers, it still remains to be seen whether ustekinumab is safe in the long term (i.e. beyond one year). It also isn’t clear whether long term use may diminish the effects of treatment. The research papers mention that the studies have been extended, and longer-term data (up to five years after treatment) will be available from both studies when ready. This follow up data should clarify these remaining issues.
The drug will be discussed by regulatory bodies in the USA in June this year and could be licensed for treatment based on these two studies. The expected cost of this treatment is not mentioned in the published studies or in the newspaper report. It is also not known if the drug is effective in reducing symptoms from the arthritis caused by psoriasis. If it is licensed, both these factors will have an impact on how this drug is used and for whom it is recommended.
Sir Muir Gray adds...
Two randomised controlled trials are impressive. What we need now is for other trials to be done and for all the results to be combined to create a systematic review, a synthesis of all the evidence.