This study assess the efficacy and safety of a new formulation of DMF (LAS41008) compared with placebo and Fumaderm in adults with psoriasis.

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Background:
Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient.

Objectives:
To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm®, in adults with moderate-to-severe chronic plaque psoriasis.

Methods:
In this phase III, double-blind, placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012-000055-13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of ‘clear’ or ‘almost clear’ in the Physician's Global Assessment (PGA) at week 16.

Results:
In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm®; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm®: P < 0·001). Overall, 33% of patients treated with LAS41008 were ‘clear’ or ‘almost clear’ in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm®. Most treatment-related adverse events were classed as ‘mild’ in severity.

Conclusions:
LAS41008 (DMF) is effective in the treatment of adults with moderate-to-severe chronic plaque psoriasis.

This study suggests the differences in the expression of CD39 and CD73 Tregs may be a factor in the pathogenesis of psoriasis.

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Background:
CD39 and CD73 are two novel cell surface markers of CD25highFoxp3+ regulatory T-cells (Tregs). Concordant expression of these two ectoenzymes not only discriminate Tregs from other cell populations, but also generates pericellular adenosine, which has been reported to suppress proliferation of activated T effector (Teff) cells. Because it is currently unclear whether human ectoenzymes (CD39/CD73) are involved in the impaired suppressive activity of Tregs in psoriasis, we examined the frequencies and phenotypes of CD39/CD73-expressing Tregs and related receptor adenosine receptor 2A (A2AR) in peripheral blood of patients with different types of psoriasis.

Methods:
Peripheral blood mononuclear cells (PMBC) were prepared from patients with three different types of psoriasis (psoriasis vulgaris, pustular psoriasis and erythrodermic psoriasis). CD4+ cells were separated from PBMC by negative selection on midiMACS columns, and the frequencies and phenotypes of CD39 and CD73 expressing Tregs, and A2AR expressing Teff were all determined by flow cytometry analysis. Blood from healthy volunteers served as controls.

Results:
The expression of single CD73+ Tregs was markedly reduced (approximately 50%) in psoriasis vulgaris, compared to normal controls. In pustular psoriasis, the mean numbers of CD39+ Tregs and A2AR+ Teff was significantly lower than in normal controls. Among three different types of psoriasis, CD39 expression was strikingly reduced in the blood Treg population of pustular psoriasis patients. Decreased CD73+ Tregs levels were observed in psoriasis vulgaris compared to pustular psoriasis and erythrodermic psoriasis.

Conclusions:
The differences in the expression of CD39− and CD73− Tregs may be a factor in the pathogenesis of psoriasis.

This population based Norwegian study looked at the increased risk of fractures in psoriasis patients.

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Background:
An association between psoriasis and osteoporosis has been reported.

Objectives:
To investigate, in a large prospective population-based Norwegian study, whether psoriasis is associated with increased risk of forearm or hip fracture; to investigate the cross-sectional association between psoriasis and bone mineral density (BMD) T-score in a subpopulation.

Methods:
Hospital-derived fracture data from Nord-Trøndelag County (1995–2013) were linked to psoriasis information, BMD measurements and lifestyle factors from the third survey of the Nord-Trøndelag Health Study 2006–08 (HUNT3); socioeconomic data from the National Education Database; and use of medication from the Norwegian Prescription Database.

Results:
Among 48 194 participants in HUNT3, we found no increased risk of forearm or hip fracture in 2804 patients with self-reported psoriasis [overall age- and sex-adjusted hazard ratio 1·03, 95% confidence interval (CI) 0·82–1·31]. No clear association was found between psoriasis and mean BMD T-score; overall age- and sex-adjusted differences in total hip, femoral neck and lumbar spine BMD T-scores were 0·02 (95% CI −0·11 to 0·14), 0·05 (95% CI −0·06 to 0·17) and 0·07 (95% CI −0·09 to 0·24), respectively. No clear association was found between psoriasis and prevalent osteoporosis in either total hip, femoral neck or lumbar spine; overall age- and sex-adjusted odds ratio was 0·77 (95% CI 0·54–1·10). Associations did not change substantially after adjustment for education, smoking, systemic steroid use and body mass index.

Conclusions:
We found no association between psoriasis and risk of fracture. The study did not indicate reduced BMD T-score or higher prevalence of osteoporosis among patients with psoriasis.

MP1032 a twice daily oral treatment for psoriasis has undergone a phase IIa trial conducted at four clinical study sites in Germany.

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MetrioPharm AG, a biotech company developing small molecule immune modulators for autoimmune and other inflammatory diseases, today announces positive top line results from its phase IIa trial with its proprietary drug compound MP1032 in patients with moderate-to-severe plaque psoriasis.

The phase IIa trial conducted at four clinical study sites in Germany was a randomized (1:1), double-blind, placebo-controlled, study with MP1032 given orally twice daily. Forty-four patients received six-weeks of treatment with placebo or MP1032 and were monitored for an additional four-week period.

The primary objectives of the study were to evaluate the safety and pharmacokinetics (PK) of twice daily 100 mg MP1032 in patients with moderate-to-severe plaque psoriasis. Enrolled patients had an average age of 40 years (21–65) and a median baseline PASI score of 13.6 (ranging from 10.1 to 40.8).

With regard to safety, the most frequently reported adverse events were common cold, headache, and itching. All events were mild to moderate in nature and occurred in both the placebo and MP1032 group. There were no effects on lymphocytes or other blood-count parameters and no treatment-related gastro-intestinal adverse effects were reported. No serious or severe adverse events were reported in patients treated with MP1032. No patient treated with MP1032 discontinued the trial because of adverse events or tolerability issues.

Exploratory analyses regarding the potential effect of the drug on PASI scores suggest that patients with MP1032 exposure levels above 120 ng*hr/ml (n=16) have a median reduction from baseline in PASI score of 25 % as compared to 12 % in the placebo group at the end of treatment (week 6). Upon discontinuation of treatment, during the four-week follow up period, median PASI scores in the treatment group trended back upward while the placebo group remained relatively unchanged, suggestive of a therapeutic effect of MP1032.

“This phase IIa study suggests a clinically meaningful activity of MP1032 for the treatment of moderate-to-severe plaque psoriasis. From a clinical point of view, an oral drug with a better tolerability profile than currently available drugs, is desirable. I am looking forward to seeing how MP1032 performs in upcoming clinical trials,” said Prof. Wolfgang Vanscheidt, one of the study’s Principal Investigators.

Dr. Wolfgang Brysch, CEO of MetrioPharm said “The positive results from this trial represent an important milestone in our development program for MP1032. We are very pleased that MP1032 was well tolerated and that there is a meaningful trend in response after only six weeks of treatment. We believe that MP1032 could become an effective, and well-tolerated oral treatment option for patients suffering from moderate-to-severe forms of psoriasis”.

Based on the wide pre-clinical safety margin of the drug, the PK data in psoriasis patients, and the trend in drug effect observed in this trial, MetrioPharm is planning a three-month phase IIb study in patients with moderate-to-severe plaque psoriasis with higher doses of MP1032.

Not sure if this is the right place, but ibuprofen has been shown to increase risk of heart attack by 31%, and diclofenac increases risk to 50%, which I thought relevant news to those of us who take them to relieve psa symptoms.
There is some kind of action on platelets and clotting in the blood. Shame because I find they relieve pain much better than paracetamol..

As I have been here a while now and my journal about Fumaderm and hormone injections is no longer relevant. As I'm clear of prostate cancer and no longer have the awful hormone injections that kept the prostate cancer under control Fumaderm and hormone injections

So I will begin my continued journey here

2 weeks ago I was invited to have an MRI scan on my brain as there we're worries that Fumaderm had been linked to cases of PML ...I told my dermatologist that my lymphocyte levels hadn't been low enough to allow any opportunistic infections to take hold....he felt that it would be wise

So today I had my 3 monthly meeting with the Dermatologist who gave me the good news that my brain scan showed no abnormalities ( I know it's hard to believe)
Also got my blood results with my lymphocyte count at 1.15 ( normal is between 1and 3 )
Kidney and liver function was normal

I have now been on Fumaderm 5 years and have found it to be a life changer for me I barely know I have psoriasis now apart from a stubborn spot on my left elbow.
I am taking 5 Fumaderm tablets a day  3 in the morning with my breakfast and 2 with my evening meal. Always with plenty of fluids .

I found 4 tablets keep my psoriasis under control, but I have increased to five a day to help control the psoriatic arthritis which it seems to be keeping it away as my sore fingers and feet are almost normal with hardly any pain

I will keep this thread updated with my continued journey and hope to keep reporting no change

[Group Specific]

I'm pleased to show some new Psoriasis Club Cards.



I have now removed the old ones so if you do use the cards you will need to download the new ones from this link:

https://psoriasisclub.org/PCcards.pdf

Once you have downloaded the PDF you can print of an A4 page with 8 cards.

*Please do not put them out anywhere without the owners consent.

*Be careful if you approach a stranger to offer a card as some people may be very concious of their psoriasis and you could offend.

I would like to thank a friend (not a member) for making the new Psoriasis Club Cards for us.

Hi All,

Apologies if this has already been discussed(i tried searching previous posts) or if i have posted this topic in the wrong place.

My background: I have suffered from pretty sever psoriasis for 6 years. I tried every sort of treatment to little or no avail, before i was turned onto Fumaderm 16 months ago. From early in the initial course, it was completely cleared. My dermatologist continued to increase my dose until i reached 6x 120mg a day. After this he slowly reduced it.

4 weeks ago i was reduced to 2x 120mg Fumaderm a day, and almost immediately i saw psoriasis return. I have been moved back to 3x 120mg a day, however it has only gotten worse.

I am just wondering if anybody has had any similar issues using Fumaderm?? I am only hoping this is temporary, maybe my daily dose was reduced too low, and now that I am back to 3x a day it will slowly go away!

Thank you in advance for any help you may be able to give!

Hi,
I'm Paul 64 and plagued by Psoriasis. Elbows Knees and back, and the cheeks of my bum!
Been using Dovobet but it's very temporary. Would like to go swimming more but not like this.
Keep scratching and make the sheets look like a bloodbath.

Any hints welcome.

Paul

Does anyone else suffer from Reynaud's Syndrome? This where the small capillaries in your extremities shut down in the cold leaving the area looking dearly white and can also be accompanied by a loss of feeling and or pain.
My middle finger and index finger on the right hand are particularly susceptible and seems to be much worse this winter since being on Acitretin. I've had a quick look on'tinternet but can't find a logical link.

This study suggests that psoriasis patients have more addictions than the general population.

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Background:
Psoriasis is a disease of enormous socio-economic impact. Despite approval of numerous highly efficient and costly therapies, a minor proportion of severely affected patients actually receives sufficient treatment.

Objective:
To investigate whether addictions are associated with psoriasis and to develop evidence-based recommendations for dermatologists in their daily clinical practice in order to improve medical assessment of psoriasis and patients’ quality of life.

Patients and Methods:
Psoriasis patients at the University Department of Dermatology were asked to fill out a paper-based self-reported anonymous questionnaire with 92 questions of validated screening tests for the six most common addictions in Germany (alcohol, nicotine, drugs and illegal drugs, gambling, food). Body weight and height as well as current Psoriasis Area and Severity Index (PASI) were documented as well.

Results:
Between October 2015 and February 2016 102 patients (65 males, 37 females; mean age 49.7 years (SD 13.4), range 18 - 83 years) participated in the study. Fifty-seven of the 102 patients showed addictive behavior. Of these 23.8% were high risk drinkers, 41% regular smokers, 11% at risk of drug abuse, 4.1% at risk of food dependency, and 19% compulsive gamblers. Compared to the general population, these results are significantly higher for alcohol abuse (p < 0.005), nicotine (p < 0.001) and gambling (p < 0.001). Body-mass-index was significantly higher in the study population (p < 0.001).

Conclusion:
Addictions and gambling are more prevalent in patients with psoriasis compared to the general population. Respective screening measures are recommended in daily practice for doctors treating psoriasis patients and PeakPASI is suggested as a score to document patients’ lifetime highest PASI. Parallel to new drug approvals and even more detailed insights into the pathomechanism of psoriasis, public health strategies and interdisciplinary approaches are essential for a general sustained psoriasis treatment.

Hi all, 

I only joined the forum today, to ask some of you good people questions about Taltz. 

Related to that, I started reading up about how the newer Interleukin-17 inhibiting biologics are proving particularly effective, and how this seems to be a promising route to getting psoriasis under control. 

I stumbled across this: LINK REMOVED

It appears Ursolic Acid is a supplement that also inhibits Interleukin-17. I wondered if anyone had heard of it, or tried it? Logic tells me it would also help get psoriasis under control, but perhaps I'm totally wrong?

This study looked at psoriasis patients in Spain and compared them with the rest of the EU.

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Background:
The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey data were not analysed to account for cultural and healthcare system differences across European countries (EC).

Objective:
Utilize MAPP data to characterize psoriasis in Spanish patients, including severity assessment and Dermatology Life Quality Index (DLQI).

Methods:
MAPP was conducted between June and August 2012. This analysis included 1700 patients with self-reported psoriasis (without psoriatic arthritis) from France (n=349), Germany (n=311), Italy (n=359), Spain (n=354) and the United Kingdom (n=327).

Results:
Patients from Spain versus other EC self-reported higher mean body mass index (26.9 vs. 25.6, P≤0.001), lower prevalence of depression (6% vs. 12%, P=0.002) and higher mean self-perceived psoriasis severity at its worst (5.92 vs. 5.33, P<0.001) despite lower estimated body-surface-area involvement. Overall, patients from Spain versus other EC had lower mean global DLQI scores (4.70 vs. 6.06, P=0.001) and mean scores for each DLQI dimension (all P<0.001, except leisure [P=0.002], treatment [P=0.002], and work and school [P=0.005]). Higher DLQI values were inversely associated with age and directly correlated with perceived severity. Palmoplantar, nail and scalp psoriasis were reported less frequently in Spanish patients (P≤0.026) and were associated with higher DLQI values (P<0.01). Spanish patients were more likely to have seen multiple healthcare providers (HCPs, P<0.001) and achieve therapeutic goals (P<0.001), but current treatments were similar to patients in other EC.

Conclusions:
In the MAPP survey, Spanish patients differed from other EC in several characteristics, including comorbidities, extent and distribution of psoriasis lesions, perception of severity and impact on quality-of-life. Their perception of psoriasis severity was higher despite a lower estimated extent, and DLQI scores were significantly lower. Spanish patients had more HCP visits and a higher rate of therapeutic goal achievement. These differences might be attributed to cultural factors, phenotypical variation and differences in HCP access.

Hi everyone, 

I wanted to introduce myself. I've had psoriasis for about 30 years, started as guttate and progressed into plaque. It's pretty much everywhere - scalp, arms, legs, front, back, ears, and even little bits on the palms of my hands. I'd been taking MTX, 10mg a week for about a year, and that had damped it down a bit. Still having flareups while on it, including a recent one which has been the mother of them all. The itching and burning is driving me mad, and it's having quite a serious affect on my mental wellbeing. 

I have my regular appointment at the hospital with the derm tomorrow (in the UK), and I'm really keen to try Taltz after what I've read about it. I wondered if anyone else is in the UK here, and managed to get it? I'm worried my request is going to get turned down. 

Any help would be very welcome.

Novartis have said that psoriasis patients rapidly regain skin clearance following a treatment pause of Cosentyx.

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Novartis announced today a new analysis showing that moderate-to-severe psoriasis patients treated with Cosentyx® (secukinumab) rapidly regain clear or almost clear skin (Psoriasis Area Severity Index, PASI 90 to 100) following relapse during a treatment pause. The analysis also showed no anti-secukinumab antibodies were observed during retreatment. These findings were presented at the 2017 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida, at which Novartis presented over 35 scientific abstracts.

Previous data has shown favorable results for continuous over intermittent treatment, however sometimes patients have treatment pauses. This new analysis shows that if psoriasis patients relapse during treatment pauses, the majority can achieve previous high levels of efficacy after only 16 weeks of retreatment with Cosentyx. Immunogenicity is a frequent issue with many biologic psoriasis treatments that lose long-term efficacy over time. Cosentyx has previously demonstrated almost zero immunogenicity. Cosentyx is a fully human, targeted treatment that specifically inhibits the IL-17A cytokine and previous data has shown that it delivers high and long-lasting clear or almost clear skin in up to 80% of patients.

"It is very clear that patients get the best results from continuous treatment," said Vas Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. "However, if for some reason treatment has been interrupted, this analysis gives patients and clinicians the peace of mind that Cosentyx is likely to help people quickly achieve clear skin once again."

For patients who achieved PASI 75 responses after one year of treatment with Cosentyx (300mg), and then relapsed after treatment discontinuation (n=136), the analysis shows that, by Week 16 of retreatment with Cosentyx, 94% of patients regained a PASI 75 score, 79% of prior PASI 90 responders (n=117) regained a PASI 90 score and 67% of prior PASI 100 response (n=67) regained a PASI 100 score. In addition, the safety profile was favorable and consistent with that demonstrated in previous studies. Furthermore, no patients in this analysis were found to have developed anti-secukinumab antibodies.

Cosentyx is the only IL-17A inhibitor approved in psoriasis, psoriatic arthritis and ankylosing spondylitis with more than 80,000 patients treated in the post-marketing setting worldwide across all indications.

A 24 week head to head study of Taltz and Stelara resulted in a Taltz win.

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Eli Lilly and Company announced today that patients with moderate-to-severe plaque psoriasis treated with Taltz® (ixekizumab) demonstrated superior efficacy at 24 weeks compared to patients treated with Stelara®* (ustekinumab).

At 24 weeks, patients treated with Taltz achieved significantly higher response rates compared to patients treated with Stelara, including 83 percent of patients who achieved Psoriasis Area Severity Index (PASI) 90—the study's primary endpoint—compared to 59 percent of patients who achieved PASI 90 after treatment with Stelara.

"For many years, achieving PASI 75 - or 75 percent improvement in skin plaques - has been the standard treatment goal for moderate-to-severe plaque psoriasis," said Kristian Reich, M.D., Ph.D., lead author and professor, Georg-August-University Göttingen and Dermatologikum Hamburg, Hamburg, Germany. "With the introduction of treatments like Taltz, dermatologists can offer treatment options that allow more patients to achieve PASI 90 or PASI 100. The data of the IXORA-S study is significant, as it demonstrates both high levels of skin improvement for patients treated with Taltz, consistent with pivotal Phase 3 trials, as well as higher response rates over Stelara, which is one of the most frequently used biologics in the treatment of moderate-to-severe plaque psoriasis."

In the IXORA-S study, patients were randomized to receive either Stelara (45 mg or 90 mg weight-based dosing per label) or Taltz (80 mg every two weeks for 12 weeks followed by 80 mg every four weeks), following a 160-mg starting dose, for a total of 52 weeks.

This study also evaluated PASI 75, PASI 100 and static Physician's Global Assessment score (sPGA) 0 or 1 with at least a two-point improvement from baseline. PASI measures the extent and severity of psoriasis by assessing average redness, thickness and scaliness of skin lesions (each graded on a zero to four scale), weighted by the body surface area of involved skin.1 The sPGA is the physician's assessment of severity of a patient's psoriasis lesions overall at a specific point in time and is a required measure the FDA uses to evaluate effectiveness.1

At 24 weeks, patients treated with Taltz achieved significantly higher response rates compared to patients treated with Stelara, as demonstrated by the following:

   91.2 percent of patients treated with Taltz achieved PASI 75 compared to 81.9 percent of patients treated with Stelara (p=0.015);
   83.1 percent of patients treated with Taltz achieved PASI 90 compared to 59.0 percent of patients treated with Stelara (p < 0.001);
   49.3 percent of patients treated with Taltz achieved PASI 100 compared to 23.5 percent of patients treated with Stelara (p=0.001).

Additionally, 86.6 percent of patients treated with Taltz achieved sPGA 0 or 1 compared to 69.3 percent of patients treated with Stelara after 24 weeks (p < 0.001).

The majority of treatment-emergent adverse events were mild or moderate. There were no statistically significant differences between treatment groups in overall treatment-emergent adverse events. The safety profile for Taltz was consistent with previous clinical trials.

"The approval of Taltz in the U.S., Canada and Europe nearly one year ago introduced a treatment option that could help patients with moderate-to-severe plaque psoriasis achieve virtually clear or completely clear skin," said Dr. Lotus Mallbris, global brand development leader, Taltz, Eli Lilly and Company. "We are thrilled with the opportunity to share this new data with dermatologists at AAD, as it reinforces the clinical benefits of Taltz for patients with moderate-to-severe plaque psoriasis."

Results from Phase 3 trials evaluating Taltz for the treatment of active psoriatic arthritis are expected to be presented later this year. Taltz is also in Phase 3 trials for the treatment of axial spondyloarthritis.

Hello everyone:  I am very new at this, so forgive me if I make any mistakes.        I am wondering if anyone here has PUSTULAR Psoriasis.  Everything I am reading seems to deal with PLAQUE Psoriasis.
Frank

Hi guys.I am on Fumaderm 120x5 tablets daily.I have severe nausea. I just start to see slight improvement on my skin but it is not that great yet. I don't know what to do because next week I have to increased to 6 tabs a day and if still don't see my skin better,Should I stopped or give it a chance little bit longer if I can manage the nausea?

Hi folks.

Well it's only been a few days now, and I don't weant to speak too soon, but drinking 6 pints of water a day has greatly reduced the flushes.

I noe get a flush about mid day and it's so light.  Bearly noticeable compared to before.

My thinking is that the vastly increased water intake is flushing it through my system quicker.

Ill keep you all updated and see how it goes.  Hopefully going up a dose soon!!!!

Many thanks to all who suggested the water intake (and I really should have known better but.....)

Well, I've been on MTX now for almost 6 years, I have never had any serious side effects and initially it worked well for me.
My current dose is 12.5mg once a week with folic acid every other day of the week.
I have blood tests and a follow up appointment with my Dermatologist every 12 weeks.
I have been monitoring my progress constantly, and the last 12 month's, the MTX has really not been working and my patches of scaling have started to re-appear.
I have been approved for Biological treatments, but the NHS are very reluctant to prescribe it for me.
I have just managed to secure an appointment, in 2 weeks time, so I am now going to try and push for an alternative treatment.
When I go on holiday and spend prolonged time in the sun, I stop taking the MTX for the duration of my stay, as the sun does the job very well and I like a few sherbets when on holiday.
My next appointment is on 14th March, I will post the achievments (or lack of) when I have had this consultation.
I have been taking MTX now for 5 years & 10 month's, so it's time for a change.

I wish all the best to everyone
Good Luck
Micky