Janssen has reported new findings about Stelara at the annual meeting of the European Academy of Dermatology and Venereology (EADV)

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Janssen has reported new findings at the annual meeting of the European Academy of Dermatology and Venereology (EADV) showing significantly better persistency and lower rates of discontinuation with STELARA® (ustekinumab) therapy in comparison to anti-tumor necrosis factor (TNF)-alpha treatments among patients participating in the Psoriasis Longitudinal Assessment and Registry (PSOLAR), a post-marketing registry following patients with moderate to severe plaque psoriasis. The analysis reports on patients starting treatment, longevity of treatment and discontinuation rates of biologic therapies, including ustekinumab, infliximab, etanercept and adalimumab.

"Finding a therapy that patients can continue long term for a lifelong disease like psoriasis is important, especially when considering the potential consequences from stopping or switching treatment," said Dr Alan Menter, Chief, Division of Dermatology, Baylor University Medical Center, USA and lead investigator. "This particular analysis of the PSOLAR registry showed higher treatment longevity and lower rates of discontinuation with ustekinumab compared with anti-TNF-alpha agents."

PSOLAR is a longitudinal, observational study evaluating safety and clinical outcomes for patients with psoriasis who are treated with or are candidates for treatment with ustekinumab, infliximab, adalimumab, etanercept and other conventional systemic agents.2 PSOLAR is funded and managed by Janssen, and has a Steering Committee that includes external experts in the field of epidemiology and psoriasis. In this analysis, duration of treatment was defined by the length in days between the first dose of treatment and discontinuation of treatment; switch to a different treatment; registry withdrawal or the most recent data collection (August 23, 2013), whichever occurred first. Persistence was assessed by Kaplan-Meier (KM) analysis for time to therapy stop/switch. Cox proportional hazard regression (HR) analysis was used to compare time to stop/switch of ustekinumab with time to stop/switch of infliximab, adalimumab and etanercept.

Separate analyses were performed for first-line use (biologic-naive patients; ie first biologic started, with start occurring on registry), second-line use (second biologic started, with start occurring on registry) and third-line use (third biologic started, with start occurring on registry) to reduce confounding associated with prior exposures. It is important to note that patients are not randomised to treatments in PSOLAR, and interpretation of the results should take into account the characteristics of longitudinal registry studies.

More patients overall were treated with ustekinumab (n=1,833) than adalimumab (n=1,303), etanercept (n=537) or infliximab (n=327). Among first-line use, significantly better persistence was observed for ustekinumab compared with other biologics (adalimumab vs. ustekinumab: HR 4.99; confidence interval (CI): 3.39-7.35; P < 0.0001; etanercept vs. ustekinumab: HR 5.59; CI: 3.77-8.29; P < 0.0001; infliximab vs. ustekinumab: HR 3.04; CI: 1.66-5.57; P = 0.0003). Similar results were observed among the second- and third-line patient groups, with ustekinumab showing better treatment longevity and fewer discontinuations than other biologics. Reasons for stop/switch were similar across all four biologics. The analyses have not yet been adjusted for differences among treatment groups such as socioeconomic factors, setting of administration (self-administration versus in doctor's office) and geographic region.

Additional PSOLAR data presentations, including multiple safety analyses of the various treatment groups, are being presented at the EADV meeting.

Amgen have released results of the ABP 501 phase 3 study evaluating the efficacy and safety of their biosimilar of Humira (adalimumab)

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Amgen today announced its Phase 3 study evaluating efficacy and safety of biosimilar candidate ABP 501 compared with Humira® (adalimumab) in patients with moderate-to-severe plaque psoriasis met its primary endpoint. The primary endpoint was the Psoriasis Area and Severity Index (PASI) percent improvement from baseline to week 16 of treatment. At week 16, the PASI percent improvement from baseline was within the prespecified equivalence margin for ABP 501 compared to adalimumab. Safety and immunogenicity of ABP 501 were comparable to adalimumab. This is the first of two Phase 3 studies intended to form the basis for global regulatory submissions for ABP 501.

ABP 501 is being developed as a biosimilar to adalimumab, an anti-TNF-α monoclonal antibody, which is approved in many countries for the treatment of inflammatory diseases, including rheumatoid arthritis, plaque psoriasis (PsO), polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease and ulcerative colitis.

"Results from Amgen's biosimilar Phase 3 plaque psoriasis study met the primary endpoint for efficacy and showed comparable safety and immunogenicity to adalimumab, which further demonstrates the Company's commitment to provide patients with access to high-quality medicines," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to continuing to leverage our experience and expertise in biotechnology to bring biosimilars to patients."

Amgen has six biosimilar molecules in development and expects to launch the portfolio starting in 2017.

Study Design:
This randomized, double-blind, active-controlled study (study number 20120263) evaluated safety and efficacy of ABP 501 compared to adalimumab in adult patients with moderate-to-severe plaque PsO. There were 350 patients enrolled and initially randomized. Among them, there were 174 patients in the ABP 501 group and 173 patients in the adalimumab group treated. One patient in the ABP 501 group and two patients in the adalimumab group were randomized but did not receive any investigational product. The primary endpoint, PASI percent improvement, was evaluated at week 16. The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale) of the lesions, weighted by the area of involvement. All assessments for a given patient were made by the same observer whenever possible.

At week 16, patients with a PASI 50 or above response will remain on study for up to 52 weeks. Patients continuing on study beyond week 16 were re-randomized in a blinded fashion such that all patients initially randomized to ABP 501 continued to receive ABP 501 and those on adalimumab either continued on adalimumab or switched to ABP 501 in a 1:1 fashion. Patients will continue on treatment until week 48, when the patients will receive the last dose of investigational product. The final efficacy assessments will be conducted at week 50 and the study will end at week 52.

I can't see this helping people with a large amount of psoriasis, but it does sound like a good idea for those with the odd stubborn patch. What do you think?

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Philips launches BlueControl, the world’s first wearable blue LED light therapy device to treat

Royal Philips, the global leader in lighting, today announces the launch of Philips BlueControl, a clinically tested wearable medical device that uses blue LED light to control mild to moderate cases of psoriasis vulgaris. It will be prescribed by physicians and available through distributors in The Netherlands, Germany and The UK from October 2014.

Philips conducted two clinical trials in partnership with the University Hospital of Aachen to investigate the efficacy and safety of Philips BlueControl to reduce the symptoms of psoriasis vulgaris. In the second trial that took place over 4 months (completed in June 2014), patients were treated for 12 weeks. The results showed a 50% reduction on average of symptoms according to the Local Psoriasis Area Severity Index (PASI) which measures the severity of psoriasis plaques (thickness, redness and scaling). No negative side-effects of the blue LED light treatment were observed.

Philips BlueControl has been developed to be easily integrated into a patient’s daily routine and reduces the need for physician’s visits. Worn simply by adjusting a strap on affected arms, legs, elbows and knees, the UV-free blue LED light therapy is enabled by 40 high-intensity blue LEDs with tailored light settings. Designed with the patient in mind, the battery-driven device can be used anytime and anywhere.

“Research proves that blue LED light treatment slows down rapid cell division6 and can also reduce inflammation.7 This research has enabled us to develop, for the first time, an unprecedented treatment device that can make a real difference to the lives of sufferers psoriasis vulgaris.” says Matthias Born, Head of Clinical Affairs for Philips’ Light and Health business.

LEDs for medical treatments require special features which exceed those of conventional LEDs, including high intensities and tailored adjustments such as pulsed LED light. Philips BlueControl is the result of rigorous research with clinical and academic partners and a complex optimization procedure to enable medical grade features to be included in a compact, easy-to-use design.

Amgen the makers of Enbrel and Brodalumab will be presenting several studies at the 23rd Congress of the European Academy of Dermatology and Venereology (EADV) in Amsterdam, Oct. 8-12, 2014.

Brodalumab data to be presented include an exploratory analysis of the Phase 2 trial evaluating efficacy and safety of brodalumab in moderate-to-severe plaque psoriasis patients with prior biologic exposure, along with an analysis from the open-label extension study of that same Phase 2 study evaluating patient response to treatment after nearly three years. Brodalumab is being co-developed by Amgen and AstraZeneca. Kyowa Hakko Kirin, which has an exclusive license to develop and commercialize brodalumab in Japan, China and certain other Asian countries, will present efficacy and safety data from its Phase 2 study evaluating brodalumab in Japanese patients with moderate-to-severe plaque psoriasis.

ENBREL data focus on step-down dosing compared with a high-dose regimen and patient-reported outcomes of treatment with ENBREL compared to treatment with ENBREL in combination with topical therapies. Additional data include the functional equivalence of proposed biosimilar ABP 501 to adalimumab and an analysis of the incidence of symptoms such as itching and pain in patients with psoriasis.

Source: NO LINKS ALLOWED

More on Enbrel (etanercept) and Brodalumab phase 3 results

My Psoriasis was 99% in control. Feb 2014 I had to stop my Humira for 2 moths while I had colon surgery.(Humira use was 2+ years) Now nothing will help and it has spread to my whole body. Currently the doc is trying Remicade for 3 months now but no results. And it is not helping my arthritis. Large swollen patches with burning feeling. Anyone else have to stop meds and go back on them to have them not work?

This study looks at the use of Propylthiouracil (PTU), an anti-thyroid thioureylene as a treatment for psoriasis.

*Propylthiouracil (PTU) or 6-n-propylthiouracil[1] (PROP) is a thiouracil-derived drug used to treat hyperthyroidism (including Graves' disease) by decreasing the amount of thyroid hormone produced by the thyroid gland. Its notable side effects include a risk of agranulocytosis and aplastic anemia. On 3 June 2009, the FDA published an alert "notifying healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil." As a result, propylthiouracil is no longer recommended in non-pregnant adults and in children as the front line antithyroid medication.

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Background:
Propylthiouracil (PTU), an anti-thyroid thioureylene, has been shown to be effective in chronic plaque psoriasis. Involucrin is a precursor protein that is upregulated in psoriasis.

Objectives:
This study evaluated the expression of involucrin in the epidermis of skin in psoriatic plaques before and after treatment with PTU.

Methods:
This was an open-label, prospective study in which 25 psoriasis patients underwent skin biopsies prior to treatment with oral PTU 100 mg three times per day for 12 weeks. Patients were assessed at 2, 6, and 12 weeks. Skin biopsies were repeated at the same sites at 12 weeks. Pre- and post-treatment specimens were subjected to immunohistochemical staining and real-time polymerase chain reaction for involucrin.

Results:
Mean ± standard deviation (SD) scores on the Psoriasis Area and Severity Index reduced significantly from 17.86 ± 9.9 at baseline to 4.63 ± 4.1 at week 12 (P < 0.001). Histomorphometric analysis revealed marked decreases in numbers of positively stained cells and intensity of staining. Staining became localized to the upper granular layers after therapy. Immunohistochemical scoring for involucrin reduced from a mean ± SD of 9.00 ± 0.67 at baseline to 3.90 ± 0.88 at week 12 (P < 0.0001).

Conclusions:
In psoriasis, there is increased expression of involucrin, which leads to abnormal keratinocyte differentiation and hence to the formation of psoriatic plaques. The therapeutic effect of PTU in psoriasis may be attributable to the downregulation of involucrin. Larger trials should further elucidate the mechanism and therapeutic potential of PTU in psoriasis.

This study published in International Journal of Dermatology Evaluated body composition parameters in patients with psoriasis.

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Background:
Body composition parameters, such as weight, body mass index (BMI), and visceral fat rating, have been found to be associated with psoriasis. However, the associations of these parameters with psoriasis have not been demonstrated clearly.

Objectives:
This study aimed to evaluate body composition parameters in patients with psoriasis.

Methods:
The relationships between the various body composition parameters and psoriasis were retrospectively examined in 242 patients with plaque psoriasis (119 women, 123 men) over a 2-year period during 2010–2012. In addition, the correlations between body composition parameters and Psoriasis Area and Severity Index (PASI) score were evaluated in treated and untreated patients with psoriasis. Patients were divided into two groups according to whether or not they had received systemic therapy within the previous three months. Body composition values were measured using the Tanita SC-330 Body Composition Analyzer®.

Results:
Statistically significant differences were recorded in terms of weight (kg), body fat percentage, fat mass (kg), total body water (TBW) percentage, metabolic age, visceral fat rating, BMI, and degree of obesity among treated and untreated patients and control subjects. Differences in fat-free mass (FFM) (kg), muscle mass (kg), TBW (kg), and bone mass (kg) were found to be close to the limit for significance. The treated and untreated groups showed no significant differences in any of the parameters evaluated. The correlations between PASI score and the various parameters provided some evidence for such relationships.

Conclusions:
The present study provides evidence of a relationship between some body composition parameters and the occurrence of psoriasis. We suggest that body composition parameters should be analyzed not only in obese psoriasis patients but in all psoriasis patients upon their first diagnosis. Systemic therapy does not appear to cause any changes in body composition parameters.

There are few threads about psoriasis ans sexual dysfunction on Psoriasis Club, but this one is the first study identifying body areas other than genitals as potentially related to sexual dysfunction in psoriasis patients.

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Introduction:
Psoriasis may significantly impair sexual function. Depression and organic factors appear to play a key role in this relationship. However, beyond genital psoriasis, the importance of the distribution pattern of the disease has not been considered.

Aim:
To investigate the role of the distribution pattern of psoriasis in sexual dysfunction.

Methods:
A prospective case series study was carried out on 133 patients with moderate to severe psoriasis.

Main Outcome Measures:
The participants completed the Massachusetts General Hospital-Sexual Functioning Questionnaire, the Hospital Anxiety and Depression Scale, and the Self-Administered Psoriasis Area and Severity Index.

Results:
Forty-four women (mean age 42.0 ± 14.1) and 79 men (mean age 47 ± 11.7) were included in the study. Psoriasis lesions on abdomen, genitals, lumbar region, and buttocks in women and chest, genitals, and buttocks in men were associated with an increase in sexual dysfunction. Multivariate logistic regression analysis showed that the involvement of these specific areas may be independent risk factors for sexual dysfunction in patients with moderate to severe psoriasis.

Conclusions:
This is the first study identifying body areas other than genitals as potentially related to sexual dysfunction in psoriasis patients. The results suggest that the assessment of sexual dysfunction and the involvement of these body areas should be considered as disease severity criteria when deciding on treatment for psoriasis patients.

I know a lot of people here prefer one over the other. I'm currently on Acitretin which other than topicals and UVB is the only treatments I've tried. I haven't gotten the results (so far) I had hoped for, it doesn't seem to be helping all that much with the psoriasis on my scalp. So, I'm preparing for my next dermatologist visit, which is a month away. I'm trying to get better educated on treatments and will be the first to say that I do NOT have a scientific mind so a lot of technical talk on meds flies right over my head. So here goes:

Medications for psoriasis.... if I understand correctly they are fighting the symptoms of psoriasis. They can help slow down cell growth but are more designed to help with the redness and flaking and hopefully decreasing it. Once you get it under control, the meds can help keep you from flaring, perhaps because of lessening the symptoms and thereby helping a body keep it under control? The side effects vary by person and can be mild or harsh. I only know about Acitretin, but since it can "damage" a baby if the woman is pregnant, one can't help but wonder what exactly they are putting in their system.

Biologics.... Seem to work the "best" and I can only base this by reading this forum and also since my dermatologist said it's an option but in his case (or perhaps insurance) it's the last treatment he goes to. Since he said he tries to start at the lowest treatment and work up to see what works, I take it that biologics (in his opinion) is the highest treatment, but the one with the highest risks. My guess (again, I guess a lot) is that would be because it can affect the immune system. I know (from here) that there are side effects (mostly flushing) but no one (here) seems overly worried about that. However, if I understand correctly, the biologics target the T-cells (not that I know what those are) and directly fight the disease where it is started.

I'm not trying to say one is better than the other, first what works best for each individual is going to be different. What I'm trying to do is understand these medications. I want to understand enough to ask the dermatologist questions and to be part of what (IF it becomes necessary) the next step would be for me. I'm not trying to have this be a debate over one being "better" than the other, but I would like to know for those who prefer one over the other, why it is they think it is the better choice for them. Also, if so inclined, why you wouldn't use one or the other.

Hi there,
well not long back from the hospital and the consultant was willing to listen. She has recommended one of three drugs: Acitreten, Ciclosporin & Methotrexate. So she explained a bit about them, (which scared the life out of me) and asked me to pick which one I preferred!
I said I needed time to make a decision as these are pretty heavy duty. So I will be seeing her again in a fortnight and in the meantime I have had blood tests done and have to do another for my kidney function.
I know I should be jumping for joy, that they are finally willing to look at this seriously but the side affects seem horrible. She has also said I would only be on Acitreten or Ciclosporin for about 6 months then I would come off and that way if I had a bad flare up I would be able to go back on. So the only one longer term would be Methotrexate.
I really feel I am between a rock and a hard place. I can't carry on the way I have, but I am really worried by the potential side effects of these drugs. I know they don't happen to everyone but it seems quite a risk , when given as she says, when I come off them the psoriasis will return. Is actually worth it for 6 months. She has said other areas of the country keep people on them longer but that isn't the policy here. Spoke to the G.P. Who says he thinks they might be worth a try as my immune system he thinks is in overdrive!
So advice please. Have many of you had any of the serious side effects of these drugs or the not so serious but unpleasant?
Any help would be appreciated.
Sandra

Hello everyone! I am new. I have been reading your posts for some time. And I was also suggested to post some words here and I do...

I am 23 years old, female. I have experienced many different treatements during last 8 years, creams, ointments, lamps, MTX and so on... then youngest biological treatment in Poland. Nothing helped. (Well, Humira solved all problems after 1st injection, Psoriasis score went down from around 60 to 0... however now I can only pay it in full by myself, which is not an option nowadays). After doing routine research through the Internet I found Psorinovo info. Ordered.

Now it is the topic I would like to share my experiences, as well as reading yours. I am on "small" dosis now, 2nd week - 2 pills 30mg / day... No side effects, as well as no effects (I hope - YET!)

I am pretty surprised theres almost no info about Psorinovo, its almost suspicious, well...
I purchased Psorex before, but found out it was more a scam than any help.

Starting my new try!
best for all!
Joana

I have added a bar and made a Tweet offering the condolences from Psoriasis Club to the family and friends of Hollie McEwen the case that Sandra mentioned here News Today.


Rest In Peace Hollie

Well, not been on here in a while.
My life has been full of highs and lows.

After stopping with dimethylfumerate went on to Humira.
Was also no sign of improvement.
My scalp is raw at the moment.

Monday I begin with a Enbrel, MTX combination.
I'm hoping this also helps ease the pain in my hands and feet.
I'm a shoe freak and miss wearing heels from time to time.

I'm feeling quite positive about the treatment so fingers crossed

Hi all,
Just had a text from my brother, informing of an article in The Daily Express re: Young woman who has killed herself as a direct result of the depression and anxiety related to psoriasis. How awful and tragic for both her and her family.
My brother has been questioning me about how I feel, as he says he knows how bad my psoriasis is at present. Of course I have reassured him but it did make me think.
Not once has a g.p. or a consultant ever asked me how I feel, how is my daily life affected etc..
Actually it effects my daily life, my relationships, work etc.. greatly.
For example: at work they have a Hoover handy for me as I flake everywhere. After sitting in long meetings, I get up and look at the floor and it is covered in my skin so I get the Hoover and clean it. At the end of the day, I Hoover at Head Office as the cleaners staff are unhappy, doesn't matter that they know it isn't contagious and actually I am so self conscious I would do it anyway. When I go to clients homes, I can see them focusing on my hands and have to first explain that my condition is not contagious before I can support them!
I am lucky I have supportive family and a husband who is very understanding, because we no longer go for meals out anymore because I shed so much skin, I do not go with him to work functions anymore as the last time I did people were incredibly rude and one person actually said, I would stay home if I looked like that!
I look and feel revolting, it is revolting! I am in pain! I am exhausted. I am at times made to feel like I am a hypochondriac. I have psoriasis in places that are too embarrassing to discuss and am uncomfortable most of the time.
So, I have often said my psoriasis did not develop until later in life, I do not know how I would have coped if it had started when I was young.
I am at the hospital tomorrow to see the Consultant, and I will be impressing on them their own guidlines. I will be impressing upon them, the difficulties we all face in daily life. I will not be fobbed off with U.V. And heavy duty steroids any longer. I know Doctors are only human, I know they make mistakes and I am not in anyway implying they are useless, just that after 8yrs of seeing them, it is time they took seriously the impact of psoriasis on daily life.

Fred: hope I put this thread in the right place, apologies if not.

Following on from my request to Tanlou about starting a new thread about going onto Humira, she has asked me to get the thread going for her as she's not sure how to start a new one.

So this thread will be about Tanlou's experience of using Humira for the first time, she will update it as she goes.

Over to you Tanlou, and thank you for sharing.

Nice site and I really approve of the concept. Impressive amount of available.
Interestingly (well to me anyway) I have had skin problems for over 40 years (I'm 58) and have been treated for excema all this time. Until my first (yes) visit to a consultant earlier this year who said it was psoriasis. TBH I thought I had both over the years but no GP can be bothered to think about anything beyond the myriad of creams and lotions to choose from. I only found out I had been using a steroid cream after 30 years. No-one had ever thought to mention it.
Having just read about Dovobet on your site-I can say the consultant who prescribed it for me never mentioned anything about how it is used.
Anyway, I am very fortunate that for most of this time it has been confined mainly to my feet, with my hands being affected for the last few years making me go back for lots of useless GP appointments. They all wanna 'cure' ya. Eventually they gave me the referral I asked for. Dovobet works so far.
I work for a disability charity and would be happy to contribute to the site, not likely to be on too regularly though, but keep up the good work.

Dealing with a lot of pain and tenderness in my heels for many months now. along with other joint pain. Can't hardly walk most morning and nights. Also having trouble getting my Enbrel. Considering I been on it ten years it shouldn't be hard to get it filled. Getting the run around with the specialty pharmacy our insurance switch to this year. They should of kept it the same didn't have any trouble with the one I was using for 10 years. Hope I get it soon. My psoriasis is flaring. Went dermatologist last month and I can't get into rheumatologist till sometime in February. Just frustrated and tired of hurting so much.

Following on from these threads: Merck highlites R&D of anti-interleukin-23 and Merck present MK-3222 findings at AAD
Merck and Sun Pharma today announced an exclusive worldwide licensing agreement for the therapeutic antibody candidate, tildrakizumab, (MK-3222), which is currently being evaluated in Phase 3 registration trials for the treatment of chronic plaque psoriasis.

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Under terms of the agreement, Sun Pharma will acquire worldwide rights to tildrakizumab for use in all human indications from Merck in exchange for an upfront payment of U.S. $80 million. Merck will continue all clinical development and regulatory activities, which will be funded by Sun Pharma. Upon product approval, Sun Pharma will be responsible for regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialization of the approved product. Merck is eligible to receive undisclosed payments associated with regulatory (including product approval) and sales milestones, as well as tiered royalties ranging from mid-single digit through teen percentage rates on sales.

“Consistent with our previously announced global initiative to sharpen our commercial and R&D focus, including prioritizing our late stage pipeline candidates, we are pleased to enter into this agreement with Sun Pharma to help realize the potential of tildrakizumab for patients with chronic plaque psoriasis,” said Iain D. Dukes, Ph.D., senior vice president, Business Development and Licensing, Merck Research Laboratories.

"Sun Pharma is very pleased to enter into this collaboration with Merck, a recognized leader in the field of inflammatory/immunology therapies, for this late-stage candidate for chronic plaque psoriasis,” said Kirti Ganorkar, senior vice president, Business Development, Sun Pharma. “This collaboration is a part of our strategy towards building our pipeline of innovative dermatology products in a market with strong growth potential.”

Well lately my knee has ballooned up it's crazy just walking to the front door seems an effort (old before my time kinda feeling)
Seen the rheumatoligist today she told me I need to lose some of my chunky tummy easier said than done ( but must be done ) she also told me to join the gym if I can afford it ( well if I'm quitting chocolate I'm sure I'll manage it) anyone with the condition use the gym? Or would I be wasting my money? of what exercises/ activities do you do?
Thanks in advance. X

Hello all
I have suffered with psoriasis for 22 years now and after trying all steroid treatment, UV treatment, tar treatment and Methotrexate I have now been given Fumaderm to try.  I am on the initial pack and concerned about the side effects it might cause. I have a friend who has been on it for 2 years and doesn't have any psoriasis now, and she looks fab for it, but just wanted to get other opinions.