Oral Thrush (oral candidiasis) is a common yeast infection of the Candida species on the mucous membranes of the mouth, this study suggests that the presence of oral thrush is higher in patients with psoriasis



Background:
Infections are known to trigger and exacerbate psoriasis. Although oral candidiasis is often clinically diagnosed, it is not always confirmed by laboratory tests such as oral cytopathology.

Objectives:
The aims of this study were to determine the prevalence of oral candidiasis in patients with psoriasis through clinical and cytopathological diagnosis and to investigate the association between oral candidiasis and psoriasis with regards to the severity of the clinical presentation and the type of treatment for psoriasis.

Methods:
A total of 140 patients with psoriasis and 140 healthy control subjects received an oral examination. Scrapings of the tongue were also obtained for a cytopathological examination.

Results:
The oral examination and the results of the cytopathological smear revealed 37 (26%) cases of candidiasis in the patients with psoriasis and no cases of candidiasis in the healthy control subjects. There was no correlation between the type of psoriasis treatment and the presence of oral candidiasis (P = .616). There was a statistically significant association (P = .033) between the clinical severity of psoriasis and the presence of Candida.

Limitations:
This study was limited by the small number of subjects and the lack of follow-up to determine the development of psoriasis after treatment for oral candidiasis.

Conclusions:
The presence of oral candidiasis is higher in patients with psoriasis and it is associated with disease severity. This increased presence of oral candidiasis was apparent despite any type of treatment for the psoriasis. Cytopathology to rule out oral candidiasis should be used in the routine medical workup of patients with psoriasis.

Source: NO LINKS ALLOWED

Other relevant posts.
Gum disease linked to psoriasis
Psoriasis and oral health
Your Tongue can say a lot

Hello,
I am new to P as I have had it only for about 6 monts. Now my joints in my fingers and toes are clearly affected. What will happen when I go to the doctor. Do I have to go to a specialist, do I have to have many x-rays or other tests et.c.

The Adacolumn is a Japanese adsorptive type extracorporeal leukocyte apheresis device that selectively adsorbs granulocytes, monocytes/macrophages by Fcγ and complement receptor bindings.

Approximately 65% of granulocytes and 55% of monocytes from the blood that passes
through the column are adsorbed. However the total number of blood cells remains constant as the removed cells are rapidly replaced by mobilisation of inactive, CD-10 negative leukocytes.



Background:
Generalized pustular psoriasis (GPP) is a chronic autoimmune disease characterized by fever, erythema, and neutrophilic pustules over large areas of the skin. GPP does not respond well to pharmacologic intervention.

Objective:
We sought to assess efficacy of selectively depleting the myeloid lineage leukocytes in patients with GPP.

Methods:
Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Eligible patients had more than 10% of their skin area covered by pustules. Treatment with oral etretinate, cyclosporine, methotrexate, prednisolone, and topical prednisolone/vitamin D3 was continued if had been initiated well in advance of study entry.
Five sessions of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn (JIMRO Co Ltd, Takasaki, Japan) were administered (1 session/wk over 5 weeks) to selectively deplete Fcγ receptor and complement receptor bearing leukocytes. Efficacy was assessed by measuring the skin areas covered by pustules at baseline and 2 weeks after the last GMA session.

Results:
One patient did not complete the first GMA session. Based on the GPP severity scores relative to entry, the overall scores improved (n = 14, P = .0027), and the area of erythroderma (P = .0042), pustules (P = .0031), and edema (P = .0014) decreased. Likewise, Dermatology Life Quality Index improved (P = .0016), reflecting better daily function and quality of life. Twelve patients were judged as responders (85.7%), and 10 patients maintained the clinical response for 10 weeks after the last GMA session without any change in medication.

Limitations:
This study was unblinded and without a placebo arm.

Conclusion:
GMA in this clinical setting was safe and effective, suggested a major role for granulocytes/monocytes in the immunopathogenesis of GPP.

Source: jaad.org

Tofacitinib is a drug being investigated by Pfizer for the treatment of rheumatoid arthritis, psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection.

In November 2012 the U.S. Food and Drug Administration (FDA) approved it for treatment of rheumatoid arthritis. Tofacitinib is an inhibitor of the enzyme Janus kinase 3. More on that here: RE: I need more Psoriasis

Background:
Tofacitinib (CP-690,550) is a novel Janus kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis.

Objectives:
This Phase 2a study aimed to assess the efficacy, systemic safety, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis.

Methods:
Two tofacitinib ointment formulations were evaluated in this multicentre, double-blind, vehicle–controlled trial (NCT01246583). Seventy-one patients were randomised 2:1:2:1 to 2% tofacitinib Ointment 1, Vehicle 1, 2% tofacitinib Ointment 2 and Vehicle 2, each administered twice daily for 4 weeks to a single fixed 300 cm2 treatment area containing a target plaque +/- one or more non-target plaques and normal skin.

Results:
The primary endpoint of percent change from baseline in Target Plaque Severity Score at Week 4 demonstrated statistically significant improvement for Ointment 1 (least squares mean [LSM] –54.4%) vs Vehicle 1 (LSM –41.5%), but not Ointment 2 (LSM –24.2%) vs Vehicle 2 (LSM –17.2%). Secondary endpoints (Target Plaque Area and Itch Severity Item) improved similarly for tofacitinib ointment vs corresponding vehicle. Adverse event (AE) occurrence was similar across treatment groups. All AEs were mild or moderate and none were serious or led to subject discontinuation. One application site AE (erythema) was reported. Tofacitinib mean systemic exposure was minimal and was greater for Ointment 1 than for Ointment 2.

Conclusions:
Tofacitinib Ointment 1 was well tolerated and efficacious compared with vehicle for the treatment of plaque psoriasis. Further study of topical tofacitinib for psoriasis treatment is warranted.

Source: onlinelibrary.wiley.com

Hello!! I have been "living" with psoriasis since May 26, 1995. I remember it because i had my 16th bday on the 4th..then i had my first baby on the 19th and i remember i had a skirt i was so excited about wearing since i had lost enough baby weight to fit into it...i was also going to look at a apartment with a friend of mine i had known since public school (kindergarten) ...i can remember it like it was this morning...

i got the skirt out and laid it on my bed..went into the bathroom to take a shower and thats when it happened...i noticed there was a long line of "spots" down my shin, i freaked out...went directly to my papa and asked him what it was, he thought it was hayfever and gave me a bunch of benedryl and sent me on my way. A few days later it covered my legs completely, most of my stomach and chest, also my arms were covered, the palms of my hands and face were just red and itchy.
psoriasis had taken over my body.

bless papa's heart he tried so hard to rid me of this horrible skin condition, taking me to any doctor he could find. My friends treated me like i had something contagious and left me to myself, the boyfriend was no help and my parents had no clue...

no one in my family has psoriasis (my father took off when i was born so i have no idea about his family...which is probably where it is from but like i say i have never had contact with them)

I have tried EVERYTHING available to me from creams, tar, UV lights, tanning beds, diet, methotrexate oral and injection and now i am at the max dose for the methotrexate injection but it makes me so unbelievably nauseas that i cannot handle it any longer, now my 10yr old has it on her scalp and face, she is mortified and rightfully so, the biggest problem i am having is she is autistic and feels pain differently then we do and she scratches the spots until she bleeds. i have not sent her to school as kids are extremely cruel and i cannot stand to subject her to that.

i need some help!
i have a dermatologist appointment for her on the 22snd of feb and hope the doc can help her...i refuse to treat mine until i can relieve her of hers.

i hope i have done my introduction properly and look forward to many conversations with the great members of this club!!

thank you for inviting me!

cheers! tammie

Galapagos a clinical stage biotech company based in Belgium today announced that GlaxoSmithKline plan to initiate Phase 2 studies with GSK2586184 (formerly GLPG0778) in systemic lupus erythematosus (SLE) and chronic plaque psoriasis.

GSK2586184 is a selective JAK1 inhibitor which was discovered and developed within Galapagos’ osteoarthritis alliance with GSK. GSK in-licensed the molecule in February 2012, gaining worldwide rights to further development and commercialization. Galapagos is eligible, without further financial investment from Galapagos, to receive from GSK €34M in additional milestones plus up to double-digit royalties on global commercial sales of all therapeutic indications of GSK2586184.

“Inhibition of JAK1 is considered a promising new therapeutic route to treat inflammatory diseases. Galapagos is leading the field with two JAK1 inhibition molecules being tested in patients,” said Onno van de Stolpe, CEO of Galapagos. “With two of our JAK1 molecules in Phase 2, we hope that this will deliver a new class of medicines to patients with inflammatory diseases.”

GSK plans to initiate a 12 week, multi-center, dose-ranging, placebo-controlled Phase 2 study investigating safety and efficacy of various doses of GSK2586184 in SLE patients. Furthermore, GSK will also initiate a 12 week multi-center, dose-ranging, placebo-controlled Phase 2 study investigating the efficacy and safety of GSK2586184 in chronic plaque psoriasis.

Source: glpg.com

This study published in the British Journal of Dermatology set out to find the cost effectiveness of topical therapies for the treatment of localised plaque psoriasis.

Background:
Topical therapies are a mainstay of psoriasis treatment, but they vary substantially in terms of costs.

Objectives:
To determine the cost-effectiveness and optimal treatment sequence for psoriasis of the trunk, limbs and scalp.

Methods:
Probabilities of response from a network meta-analysis were used to determine the short-term efficacy of topical therapies. Longer-term outcomes, including relapse, were informed by published evidence and clinical opinion. Benefits of treatment were measured as quality-adjusted life years (QALYs). Direct costs included topical agents, primary and secondary care visits and second-line therapies for treatment failures.

Results:
For trunk and limbs, initial treatment with two-compound formulation (TCF) product containing vitamin D and potent corticosteroid provided the most QALYs, followed by separate morning and evening application of vitamin D and potent corticosteroid (TCA (am/pm)), and then twice daily potent corticosteroids. Twice daily potent corticosteroid was the most cost-effective first-line strategy (ICER £20,000 per QALY), followed by TCA (am/pm) (£22,658 per QALY) and TCF product (£179,439 per QALY). For scalp psoriasis, initial treatment with very potent corticosteroids generated the most QALYs, followed by TCF product and then potent corticosteroids. Very potent corticosteroids were most cost effective, but if too aggressive, then potent corticosteroids were optimal followed by TCF product (£219,846 per QALY). Cost effectiveness of second and third-line topical agents varied with assumptions made.

Conclusions:
Potent corticosteroids, used alone or in combination with vitamin D are most cost-effective for patients with psoriasis of the trunk and limbs. Potent or very potent corticosteroids are most cost-effective for patients with scalp psoriasis.

Source: NO LINKS ALLOWED

Topical therapies are applied directly to the skin.

This thread explains the difference between Dovobet And Dovonex https://psoriasisclub.org/showthread.php?tid=75

Hi my  name is Ladonna but everyone call me Ms Donna. I have been married for 13 years in May my anniversary I have 4 children two men and set of teen girls age 12 . What keeps me grounded with my psoriasis is music.

I'm new here and I'm just looking for answers.

This article published in the British Journal of Dermatology set out to assess the efficacy and safety of different doses of Novartis AIN457 (secukinumab) for the treatment of moderate-to-severe plaque psoriasis.

Background: 
Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long-term safety. Interleukin (IL)-17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity.

Objectives: 
To assess the efficacy and safety of different doses of secukinumab, a fully human anti-IL-17A IgG1κ monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.

Methods: 
Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12-week treatment period, patients entered a follow-up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator’s Global Assessment (IGA) and PASI 90 and 50 response rates.

Results: 
After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow-up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow-up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort.

Conclusions: 
Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate-to-severe psoriasis.

Source: NO LINKS ALLOWED

Novartis AIN457 (secukinumab) Phase II Report: https://psoriasisclub.org/showthread.php?tid=237

Do you think a daily text message could help you with your psoriasis? A study published in the British Journal of Dermatology suggests that a daily text message providing reminders and educational tools could help!

Background: 
Psoriasis is a chronic disease which requires long-term therapy. Therefore, adherence to therapy and patient motivation are key points in controlling the disease. Mobile-phone-based interventions, and in particular text messages ™, have already been used effectively to motivate patients and improve treatment adherence in many different chronic diseases such as diabetes, cardiovascular disease and asthma.

Objectives: 
To evaluate the use of TM in improving treatment adherence and several patient outcomes such as quality of life, disease severity, patient-perceived disease severity and the patient–physician relationship.

Patients and methods: 
Daily TM, providing reminders and educational tools, were sent for 12 weeks to a group of 20 patients with psoriasis. At the beginning and end of the study the following assessments were performed: Psoriasis Area Severity Index (PASI), Self-Administered Psoriasis Area Severity Index (SAPASI), body surface area (BSA), Physician Global Assessment (PGA), Dermatology Life Quality Index (DLQI), evaluation of patient–physician relationship and adherence to therapy. A matched control group of 20 patients with psoriasis was used for comparison of the same outcomes.

Results: 
Both patient groups had similar scores for PASI, SAPASI, BSA, PGA and DLQI at baseline. However, after 12 weeks the intervention group reported a significantly better improvement of disease severity as well as quality of life, showing lower values of PASI, SAPASI, BSA, PGA and DLQI with respect to the control group (P < 0·05). Moreover, adherence to therapy improved in a statistically significant way (P < 0·001) whereas it remained stable in the control group. Similarly, TM interventions led to an optimization of patient–physician communication.

Conclusions: 
TM interventions seem to be a very promising tool for the long-term management of patients with psoriasis, leading to an increased compliance to therapy, positive changes in self-care behaviours and better patient–physician relationship allowing improved clinical outcomes and better control of the disease.

Source: onlinelibrary.wiley.com

This report from The British Journal of Dermatology shows nine out of ten sunbeds surveyed in England emitted levels of UV radiation that exceed the maximum levels contained within the European standard.

Background: 
Exposure to ultraviolet (UV) radiation from sunlight is recognized as the principal cause of skin cancer. Moreover, sunbeds have been classified as carcinogenic by the International Agency for Research on Cancer. Despite this, there is a shortage of objective data on UV exposure levels in sunbeds in England.

Objectives: 
We set out to measure UV emission levels in sunbeds at sites around England, and to compare these levels with both current standards and natural sunlight.

Methods: 
Between October 2010 and February 2011, UV spectra were measured on site from a total of 402 artificial tanning units in England. Measurement instrumentation was calibrated, traceable to the National Physical Laboratory. Compliance with the relevant British and European standard was determined, and a skin-cancer weighting factor was used to compare the carcinogenic potential of sunbeds with that of sunlight.

Results: 
For compliance with the European standard, erythemal-effective irradiance should not exceed 0·3 W m−2. The values that we measured ranged between 0·10 and 1·32 W m−2 with a mean of 0·56 ± 0·21 W m−2. Only 10% of sunbeds surveyed were within the recommended limit. Application of the skin-cancer weighting factor produced values that varied from 0·17 to 2·52 W m−2 with a mean of 0·99 ± 0·41 W m−2. The comparable value for Mediterranean noonday sun was 0·43 W m−2.

Conclusions: 
Nine out of 10 sunbeds surveyed throughout England emitted levels of UV radiation that exceed the maximum levels contained within the European standard. Moreover, the skin cancer risk for comparable times of exposure was up to six times higher than that for Mediterranean sunlight. This situation is unacceptable and stricter control measures must be put in place.

Source: onlinelibrary.wiley.com

I've been playing with a new feature "Random Thread"

It's only available to members that are logged in, and you can find it on the menu at Random Thread and in the footer at Random.

Just click it and you should be taken to a random thread from the forum that you may have missed.

Any problems or questions please let me know.

Biocon India's largest biotechnology company by revenue announced today that it has received Marketing Authorization from the Drugs Controller General of India (DCGI) for its Novel Biologic Itolizumab, anti CD6 molecule, for the treatment of chronic plaque Psoriasis.

Quote:

---

Itolizumab, is a first in class therapy with a unique Mechanism of Action (MOA) and an excellent safety profile as indicated during the 52 week Phase III multi-centric clinical study conducted in India. It is the second Novel Biologic developed by Biocon at Asia’s largest Biotech hub in Bangalore.

This approval paves the way for the launch of Biocon’s Alzumab in India, later during 2013. Alzumab is a differentiated biologic drug with a superior safety profile compared to other approved biologic therapies given its very low opportunistic infection rates. A novel biologic indicated for the treatment of Moderate-to-Severe Psoriasis, Alzumab will be marketed by Biocon’s Immunotherapy Division. Alzumab, will be manufactured and formulated as an infusion drug at Biocon’s Biopharma manufacturing facility at Biocon Park, Bangalore.

Commenting on this development Ms. Kiran Mazumdar-Shaw, Chairman & Managing Director, Biocon said, “We are very excited to receive this marketing authorization for Itolizumab from DCGI which will enable Biocon to introduce this novel, first in class biologic for the treatment of psoriasis patients in India. This is our Second novel biologic that we have developed in India, BioMab EGFR, an anti-cancer monoclonal antibody, being the first. This approval paves the way for us to extend clinical development for other indications like Rheumatoid Arthritis (RA), Multiple Sclerosis (MS) and Vitiligo. We also intend to file a US IND shortly to enable us to embark on a global clinical development plan. This is a defining moment for Biocon as it reaches a significant milestone in its mission of delivering affordable innovation to patients worldwide.”

I have a mild case of scalp psoriasis that is one persistant mofo' and it's recently developed in my ears,i had no idea that could even happen.. and every now and again minor lesions appear on my legs or elbows or even my face and every timethese minor lesions appear itry to apply just som regular cream asmuch as i can because the ointments tend to bleach skin, something i learned the hard way. Any whoo i recently had a baby, and so i have all the creams and lotions and everything of the likes to take care of her beautiful baby skin, and sooo finally to the grain: i started to get a patch of psoriasis on my chin and i tried to put on normalface cream at every hour of the day and nothing helped, when finally...this might sound odd...but i put some diaper rash cream on it during the night, and i woke up and it was gone. So tonight i'm going to try and use the diaper rash cream on more of my skin to see if it can help because i've been living for years with this psoriasis that nothing else can help.
Try it! Baby diaper rash ointment.

I have never been told that I have psoriatic arthritis, but lately I have some swelling around my thumb joint (top of thumb). It doesn't hurt really, but is hot. Is this one of the symptoms to psoriatic arthritis?

Has anyone here had any odd internal problems? I have had chronic Pancreatitus. I just seems odd to me that I have P and PA and also another rare condition the Pancreatitus. My Gastro Dr. claims that there is no connection but I am sceptic. Right now I sit here with my gut jutting out swelled up and half luppy from Oxycotten.

Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that, in 2011, tumor necrosis factor-alpha (TNF-alpha) inhibitors dominated sales in the psoriatic arthritis (PsA) drug market, contributing to 89 percent of the nearly $1.7 billion PsA market in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan.

The upcoming Pharmacor advisory service entitled Psoriatic Arthritis, which will be published soon, finds that the TNF-alpha inhibitor etanercept (Amgen/Pfizer/Takeda's Enbrel) was the 2011 market leader, leading by a small margin over adalimumab (Abbott/Eisai's Humira). Decision Resources expects Humira to displace Enbrel as the sales leader in 2012, with its patient share surpassing that of Enbrel in 2013.

"Interviewed thought leaders believe that Humira's superior efficacy on skin symptoms over Enbrel, its excellent efficacy on joint symptoms, twice-monthly dosing and years of physician experience for treating PsA will continue to drive its uptake in this market," said Decision Resources Analyst Bingnan Kang, Ph.D.

The findings also reveal that methotrexate (Dava Pharmaceuticals' Rheumatrex, generics) was the patient-share leader in 2011 but comprised only 4 percent of total PsA sales, owing to the availability of inexpensive generics. Other conventional disease-modifying antirheumatic drugs are also highly genericized and represented only a small percentage (less than 6 percent) of market sales in 2011.

Over the next decade, four branded therapies will enter the market and will represent over one-third of the total PsA market in 2021. Of these agents, three emerging therapies offer novel mechanisms of action--the interleukin-12/23 inhibitor ustekinumab (Janssen's Stelara), the selective costimulation inhibitor abatacept (Bristol-Myers Squibb/Ono Pharmaceutical's Orencia) and the phosphadiesterase-4 inhibitor apremilast (Celgene). During this time, the TNF-alpha inhibitor certolizumab pegol (UCB/Astellas's Cimzia) will also enter the PsA market.

Source: NO LINKS ALLOWED

Idera Pharmaceuticals today announced that 48% of patients with moderate-to-severe plaque psoriasis (12 of 25) treated with IMO-3100, a selective antagonist of Toll-like Receptors (TLRs) 7 and 9, demonstrated improvements in Psoriasis Area Severity Index (PASI) scores of 35% to 90% from baseline at the completion of a randomized, double-blind, placebo-controlled Phase 2a clinical trial of two dose levels of IMO-3100 administered for four weeks, with a four-week follow-up period. None of the 12 placebo-treated patients had improvement in this range; this difference was statistically significant (p<0.005). The Company believes the results of this trial provide clinical proof-of-concept for the mechanism of action of selective TLR inhibition in patients with psoriasis and potentially other autoimmune and inflammatory disorders.

“The clinical activity of IMO-3100 demonstrated in patients with moderate-to-severe plaque psoriasis is encouraging, especially given the short duration of treatment in this study that was designed for initial explorations of safety and efficacy,” commented Alexa Kimball, M.D., M.P.H., Vice Chair, Department of Dermatology at Massachusetts General Hospital, Boston, and an investigator in the trial.

“The achievement of statistically significant PASI reductions with only four weeks of treatment in a placebo-controlled double-blind trial directly supports the rationale that the modulation of specific TLRs plays a key role in the treatment of psoriasis and, potentially, other autoimmune and inflammatory disorders,” commented James Krueger, M.D., Ph.D., of The Rockefeller University, New York. “We are excited to see these data, which demonstrate the translation of targeting a novel mechanism of action into clinical activity and support further studies of TLR antagonists for the treatment of psoriasis. Our laboratory is continuing to evaluate the immunological pathways by which TLR antagonists suppress the signaling cascades that underlie psoriasis and have the potential to open up a new approach to disease treatment.”

About the IMO-3100 Phase 2 Trial in Psoriasis:
The Phase 2 trial was a randomized, double-blind, placebo-controlled trial of IMO-3100 in patients with moderate-to-severe plaque psoriasis. In the trial, 44 patients were randomized to receive IMO-3100 monotherapy at 0.16 or 0.32 mg/kg or placebo by subcutaneous injection once weekly for four weeks with four weeks of follow-up. Assessments of safety were performed throughout the treatment and follow-up periods. Multiple parameters were monitored to assess the clinical activity of IMO-3100, including Psoriasis Area Severity Index (PASI), mean focal psoriasis severity and Physician Global Assessment (PGA) scores. In addition to the clinical assessments, biopsies of psoriasis plaques were evaluated for treatment-related changes in epidermal thickness and immune cell infiltrates consistent with the intended mechanism of action. Patients were enrolled at eleven sites in the United States.

Top-line clinical results from this trial include:
Of the 44 enrolled patients, 40 were clinically evaluable at the end of the four-week treatment period and 37 were evaluable following the four-week follow up period.

Treatment at both IMO-3100 dose levels was well tolerated, with no treatment-related discontinuations.
   
Among evaluable patients, the median PASI scores at treatment initiation were 14.9, 16.1, and 12.5 in the 0.16 mg/kg, 0.32 mg/kg, and placebo cohorts, respectively.
   
A treatment effect was demonstrated in measures of clinical efficacy in patients in both IMO-3100 dose cohorts; PASI reductions at both dose levels were sustained throughout the four-week follow-up period.
   
At the end of the four-week follow-up period, 48% of patients treated with either dose of IMO-3100 (12 of 25) demonstrated improvements of 35% to 90% from baseline PASI scores compared with 0 of 12 in the placebo cohort; this difference was statistically significant (p<0.005)
   
The trial achieved the pre-specified clinical endpoint of reduction in PASI scores at the end of treatment in the 0.16 mg/kg dose cohort with statistical significance (p<0.02) compared to the placebo cohort, but not in the 0.32 mg/kg dose cohort.
   
The 0.16 mg/kg cohort also achieved, with statistical significance (p<0.02), the pre-specified clinical endpoint of improvement in induration, a measure of plaque thickness, at the end of treatment and during the follow-up period.
   
At the end of the four-week follow-up period, 25% (3 of 12) of patients treated with 0.16 mg/kg dose and 31% (4 of 13) with 0.32 mg/kg dose achieved PASI 50 or greater, compared to 0 of 12 placebo patients.

Skin biopsies were collected at baseline and after completion of treatment to investigate changes in epidermal thickness and immune cell infiltrates. Change in epidermal thickness was the primary endpoint for the trial. Placebo treated patients had a median change in epidermal thickness of +7.7% compared to a median change of -6.4% among IMO-3100 treated patients; this difference was not statistically significant. A known limitation of skin biopsies after four weeks of treatment is that psoriatic plaques do not resolve in a uniform fashion, and therefore, biopsies may not provide a representative sampling of lesions (ref: Ann Rheum Dis 2005;64:65-68).

The Company plans to present complete clinical data from this trial at an upcoming medical meeting.

“We believe this trial in patients with moderate-to-severe plaque psoriasis provides clinical proof-of-concept for this first-in-class TLR antagonist, which represents a novel approach to the treatment of autoimmune diseases. We are very pleased to have observed clinical responses after only four weeks of treatment,” stated Sudhir Agrawal, D. Phil., Chief Executive Officer of Idera. “The insights gained from this trial support expansion of our TLR antagonist program for the treatment of autoimmune diseases. In 2013, we plan to advance the clinical development of a selective TLR antagonist for the treatment of moderate-to-severe plaque psoriasis and also for the treatment of lupus.”

Source: iderapharma.com

Previous thread on IMO-3100: Idera announce phase 2 trial of IMO-3100

Actelion announced today that its selective S1P1 modulator, ponesimod, successfully met the primary endpoint - the proportion of patients with at least 75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI75) at week 16 - in a double blind, placebo-controlled study conducted in 326 patients with moderate to severe chronic plaque psoriasis.

Results of the primary endpoint were highly statistically significant with both tested doses. With Ponesimod 20 mg, 46 % of patients improved by at least 75 % at week 16 (p<0.0001 versus placebo). With Ponesimod 40 mg, 48.1% of patients improved by at least 75 % at week 16 (p<0.0001 versus placebo). An improvement by at least 75 % was observed at week 16 in 13.4% of the placebo treated patients. Both doses were administered once daily.

At the end of induction, ponesimod patients improving at least 50% or more in their PASI score at week 16 were re-randomized to either continuation of the same dose of ponesimod, or to placebo.

After the initial 16 week induction phase of the study, further improvement was seen with ponesimod during the 12-week double-blind, placebo-controlled maintenance period. Among patients continuing on ponesimod 20 and 40mg, 71 % and 77 % achieved PASI75 at the end of the study, respectively.

Efficacy was also demonstrated across other endpoints of the study, including Physician Global Assessment (PGA) at week 16.

Guy Braunstein, M.D. and Head of Clinical Development at Actelion commented: "This is the first time that this mechanism has demonstrated efficacy with psoriasis patients. Analysis during the maintenance period of the study showed patients continued to improve beyond the initial 16 week induction phase. Having conducted such a large Phase II study we have the information we need for the design of the pivotal Phase III program."

Safety and tolerability data from the study are consistent with the safety profile of ponesimod observed in previous studies conducted including the Phase II study with multiple sclerosis patients. At initiation of ponesimod treatment, transient reductions in heart rate and less frequently, a transient effect on atrioventricular conduction were observed in the study as expected. The most frequent adverse events (AEs) reported for ponesimod was dose-dependent dyspnea and asymptomatic liver enzyme elevations. Overall, there were no indications of an increased infection rate with ponesimod in the study with the exposure to ponesimod up to 28 weeks. The safety data-base from all studies with ponesimod, now comprises more than 1,100 patients and healthy volunteers with some patients treated for up to 3.3 years.

Jean-Paul Clozel, M.D. and Chief Executive Officer commented: "We are excited to now know that ponesimod, originating from Actelion's discovery effort, has the potential to become an important treatment option in immune-mediated disorders in addition to multiple sclerosis. Actelion will rapidly move forward with the preparation of the pivotal program and discussions with health authorities for the psoriasis indication."

Once full data analysis has been concluded, Actelion will discuss the details of the upcoming Phase III program with health authorities. Actelion will present the results of this dose-finding study through scientific presentations and publications.

Source: NO LINKS ALLOWED