Background:
Tumor necrosis factor inhibitory agents are currently considered to be contraindicated in psoriatic patients with *hepatitis B.

Objective:
We aim to provide guidance to dermatologists on the use of tumor necrosis factor inhibitor therapy in these patients.

Methods:
The current literature was reviewed regarding the use of tumor necrosis factor-alpha inhibitory agents Atanercept (Enbrel), Adalimumab (Humire), and Infliximab (Remicade) in psoriatic patients with particular reference to hepatitis B infection.

Results:
Tumor necrosis factor-alpha inhibitor therapy may result in reactivated hepatitis B in hepatitis B surface antigen-positive patients with psoriasis. This also occurs, although less frequently in patients with an isolated positive hepatitis B core antibody. Thus, all psoriasis patients should be screened for hepatitis B surface antigen plus hepatitis B core antibody prior to the initiation of tumor necrosis factor-alpha inhibitor therapy. Infliximab (Remicade) has been associated with more reactivation cases than the other 2 agents and fatalities have been reported with this agent. Evidence is presented that the risk of reactivation can be greatly minimized or eliminated by early or pre-emptive antiviral therapy.

Limitations:
The data is largely based on small case series that are retrospective in nature.

Conclusions:
Hepatitis B screening is essential prior to the initiation of tumor necrosis factor-alpha inhibitor therapy. Psoriatic patients found to be hepatitis B surface antigen or hepatitis B core antibody-positive should be referred to an appropriate specialist for evaluation and therapy. This would allow for the safe use of tumor necrosis factor-alpha inhibitors in psoriatic patients despite recently published guidelines to the contrary.

Source: eblue.org

*Hepatitis B is an infectious inflammatory illness of the liver and causes liver inflammation, vomiting, jaundice and, rarely, death.

Profiles of *Dental Caries and *Periodontal Disease in Individuals With or Without Psoriasis

Background: Studies of oral health in psoriasis patients are limited. The aim was to assess the experience and risk of caries and periodontal disease in psoriatics and non-psoriatics.

Material and Methods: The material consisted of 89 individuals with mild to moderate chronic plaque psoriasis and 54 non-psoriatics, recruited at the University Hospital in Gothenburg. Psoriasis arthritis was diagnosed in 25 of the psoriatics. All participants answered questionnaires and were subjected to saliva sampling and oral radiological and clinical examinations. Two computer applications were used for illustration of oral disease risk profiles.

Results: Psoriatics had lower salivary pH, fewer remaining teeth, fewer sites with probing pocket depth ≤4 mm and a lower radiographic alveolar bone level than non-psoriatics (p<0.05). Most of the differences remained significant after controlling for confounders. Differences in alveolar bone levels were no longer significant, particularly after introducing “gender” into the regression model. Similar numbers of decayed and filled teeth, sites with deep pockets, sites that bled on probing and risk profiles were observed. Individuals with psoriasis arthritis exhibited a lower stimulated salivary secretion rate than non-psoriatics (p<0.05).

Conclusions: There were no differences in profiles of caries and periodontal disease experience and risk between individuals with and without psoriasis. Fewer remaining teeth were observed in psoriatics. However, the exact reason for tooth loss could not be identified. Meanwhile, the reduced salivary pH in psoriatics and salivary secretion in psoriasis arthritis individuals, may pose a risk for future caries.



*Dental caries, also known as tooth decay or a cavity, is an infection, usually bacterial in origin, that causes demineralization of the hard tissues (enamel, dentin and cementum) and destruction of the organic matter of the tooth.

*Periodontal disease is a type of disease that affects one or more of the periodontal tissues that both surround and support the teeth.

Hybrigenics bio-pharmaceutical company, with a focus on research and development of new treatments against proliferative diseases, announces the first results of the placebo-controlled double-blind clinical Phase II efficacy study of oral inecalcitol at the single dose of 4 mg per day in moderate to severe psoriasis.

Of the total 60 enrolled patients, 57 (20 placebo and 37 inecalcitol) have completed their treatment for at least 10 weeks and up to 16 weeks. One early study withdrawal was due to grade 3 hypercalcemia caused by inecalcitol within the first week of treatment. Of the 37 patients treated with oral inecalcitol, 24 patients (65%) showed a PASI 50 response and, among them, 10 patients (27%) had a PASI 75 clinical improvement. However, these results were not statistically different from the placebo group, in which women had an unexpectedly strong improvement of their disease with a PASI 75 rate of 63% vs. 17% observed in placebo-treated men, which is more in line with usual values from the literature on psoriasis studies of similar duration.

Blood levels of inflammatory biomarkers such as IL-4, IL-10, IL-12, IL-17, interferongamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) are currently being assayed in samples from all patients, as well as the levels of vitamin D receptor in white blood cells. Biopsies of skin lesions have been taken in subsets of patients and their histopathological examination is also ongoing.

This additional data will be available in the coming weeks and may shed some light on the reasons for the strong placebo effect observed in women, and why there weren’t more PASI 50 responders progressing to PASI 75 clinical improvement.

During the entire treatment period (16 weeks) and still one month later, after the follow-up period, the PTH levels of each of the 20 patients on placebo changed by less than 50% from their initial value and remained within the normal range. By contrast, the PTH levels of each of the 37 patients receiving inecalcitol decreased by more than 50% during the treatment.

PTH levels were decreased below the normal range in 34 inecalcitol-treated patients (92%) and below LoQ in 24 of them (65%). This PTH lowering effect was highly statistically significant as compared with placebo at all times during treatment (p< 0.001), even as soon as week 4, the earliest time point measured. This pharmacological effect of inecalcitol was totally and rapidly reversible because all PTH levels were back within the normal range after the one-month followup period.

“Two-thirds of inecalcitol-treated psoriasis patients showed some degree of response (PASI 50) but only one fourth had a clinically-relevant improvement (PASI 75) at week 12 or at week 16. A hypothesis could be that a longer duration of treatment might be necessary for inecalcitol to fully improve all the responders”, commented Dr Jean- François Dufour-Lamartinie, Hybrigenics’ Head of clinical R&D. He added: “the confirmation of inhibition of normal PTH secretion by inecalcitol, a fast, strong and straightforward effect observed in all treated patients, without any placebo effect, deserves further clinical investigation in chronic kidney disease patients who suffer from pathologically elevated PTH levels”.

Source: hybrigenics.com

An international team of scientists led by principal investigator Richard L. Gallo, M.D., Ph.D., professor of medicine and chief of UC San Diego’s Division of Dermatology, analyzed skin biopsies of patients with and without psoriasis, as well as the skin of mice with psoriasis and with wounds on their backs. They discovered that a molecule called regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in skin cells during psoriasis and wound-healing, but not under normal skin conditions.

In tests on mice, researchers found that inhibiting REG3A slowed wound-healing but cleared up psoriasis, which is commonly characterized by patches of inflammation and white, scaly skin.

The scientists also noted that REG3A acts in concert with interleukin-17 (IL-17), an immune system protein involved in the signaling cascade which prompts skin cells to multiply in excess numbers. “IL-17 binds to receptors on skin cells and causes REG3A to be expressed, which then binds to another protein inside the cells that promotes cell growth,” said first author Yuping Lai, Ph.D., professor of microbiology and immunity at East China Normal University in Shanghai.

Gallo said the discovery of REG3A’s dual roles provides a new target for different therapies.

“A drug that inhibits the expression of REG3A could represent a more targeted way to treat psoriasis without the systemic immunosuppression problems of current treatments. Conversely, a drug that stimulates or mimics REG3A could boost cell growth and improve wound healing.”

Source: universityofcalifornia.edu

The Medical College of Wisconsin received a two-year, $200,000 grant from the National Psoriasis Foundation to study the pathogenesis of psoriasis and to identify new drugs that may benefit patients.

Sam Hwang, MD, PhD, and Thomas J. Russell Family/Milwaukee Community Dermatologists Chair and professor of dermatology, is the principal investigator for the grant.

Approximately 7.5 million Americans are living with psoriasis, an autoimmune disease in which dead skin cells accumulate and cause irritation that appears as itchy scales or dry patches. Symptoms can be treated, but there is no cure, and the severity of the disease ranges from mild discomfort to complete disability. Complications include arthritis, ischemic heart disease, and depression. Dr. Hwang’s lab identified two proteins (a chemokine receptor called CCR6 and it binding protein) in prior studies of psoriasis development that appear to have significant involvement in the disease.  In this study, Dr. Hwang will investigate these proteins further to better understand how they impact the pathogenesis of psoriasis.  Dr. Hwang will also use computer modeling to discover drugs that may block the actions of these proteins and thus, potentially, improve therapy for patients with this disease.

This study may verify a pathway for psoriasis and provide new information about its cause. The project may also identify new treatments for psoriasis and other diseases influenced by the proteins Dr. Hwang is investigating.

This special award is called the Lutto Translational Grant in honour of Seymour and Rebecca Lutto, who made this research possible with a gift to the National Psoriasis Foundation. They sought to memorialise their son Lawrence Lutto by advancing scientific knowledge regarding the cause and treatment of psoriasis.

Source: mcw.edu

Objective: 
To assess the risk of incident diabetes mellitus (DM) in patients with psoriasis and to evaluate DM treatment patterns among patients with psoriasis and incident DM.

Design: 
Population-based cohort study.

Setting: 
United Kingdom–based electronic medical records.

Patients: 
We matched 108 132 patients with psoriasis aged 18 to 90 years with 430 716 unexposed patients based on practice and time of visit. For our nested study, only patients who developed incident DM during our study time were included.

Main Outcome Measures: 
Incident DM and adjusted risk of pharmacotherapy among those with incident DM.

Results: 
The fully adjusted hazard ratios (95% CIs) for incident DM were 1.14 (95% CI, 1.10-1.18), 1.11 (95% CI, 1.07-1.15), and 1.46 (95% CI, 1.30-1.65) in the overall, mild, and severe psoriasis groups, respectively. Among those with incident DM and severe psoriasis, the adjusted risk for receiving DM pharmacotherapy was 1.55 (95% CI, 1.15-2.10).

Conclusions:
Our results suggest that psoriasis is an independent risk factor for the development of type *2 DM in a dose-dependent manner, and that patients with severe psoriasis who develop DM are more likely to receive systemic diabetic therapies in comparison with patients with DM but without psoriasis.

Source: archderm.jamanetwork.com

* Diabetes mellitus type 2 is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. This is in contrast to diabetes mellitus type 1 in which there is an absolute insulin deficiency due to destruction of islet cells in the pancreas. The classic symptoms are excess thirst, frequent urination, and constant hunger. Type 2 diabetes is initially managed by increasing exercise and dietary modification. If blood glucose levels are not adequately lowered by these measures, medications such as metformin or insulin may be needed.

Hiya just found this on my weekly psoriasis google, has anyone ever heard of it before?  I don't like buying things unless I've had a recommendation. Although I am getting to the point where I will try anything.



Ossie gold soap bars

Hello everyone

I have just joined and thought I would tell you a little about myself. I'm Tamsin in 25 and was diagnosed with psoriasis when I was 18. I used to have it very badly and all over includin my face, but since getting older it has become milder. I now tend to get it on my elbows, legs and scalp but in small patches.

I'm sure you have heard it all before but I've found it really hard to cope with psoriasis and have generally quite low self esteem. I don't like to go out wearing clothes that show my spots of psoriasis. I have learned to cope with the fact I have it but still find showing it in public quite hard. And hence my single status, being worried about what men will say has put me off dating at the moment! Lol sounds rediculous now I'm telling someone!

Apart from that I'm generally a happy, healthy person and I enjoy jogging and eating healthily. I have a job that I love although it is a renowned professional for its stressful nature haha the big old STRESS word we all hate!

I hope to make some friends here, it's always nice to talk to people who understand what it's like

Well that's me, please feel free to reply

Hi my names lesley.i used to be a member here.i do remember some if you especially you fred.i cant remember my old user name.anyway I was on twitter and I found you all again.im from glasgow have had psorisis for over 4 years now but its under control with MTX.hope everyone on here is good hope I can get online a bit and chat to you all.much love lesley x

Summary Background: 
Psoriasis is a Th1 immune-mediated, inflammatory disease, in which skin lesions appear many years before the related metabolic and cardiovascular comorbidities, according to the theory of the ‘psoriatic march’. Inducible nitric oxide synthetase (iNOS), tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) are directly implicated in determining both skin lesions and systemic involvement in psoriasis. Reactive oxygen species actively promote the secretion of inflammatory Th1 cytokines directly involved in the pathogenesis of psoriasis.

Objectives: 
Evaluation of VEGF expression and production, nitric oxide (NO) production, iNOS expression, and the antioxidant response of mesenchymal stem cells (MSCs), both before and after 12 weeks of treatment with the TNF-α inhibitors adalimumab or etanercept.

Methods: 
Biochemical, morphological and immunohistochemical analyses were performed in MSCs isolated from nonlesional, perilesional and lesional skin of patients with psoriasis, before and after treatment.

Results: 
The treatments were able to reduce the expression and production of VEGF, the expression of iNOS and the production of NO in MSCs of patients with psoriasis. TNF-α inhibitors also reduced the oxidative damage in MSC membrane and proteins, several antioxidant systems responded to treatments with a general inhibition of activities (glutathione S-transferase and catalase) and these effects were also supported by a general decrease of total oxyradical scavenging capacity towards hydroxyl radicals and peroxynitrite.

Conclusions: 
TNF-α inhibitors are able to change the physiopathological pathway of psoriasis, and our results suggest their therapeutic effects already take place at the level of MSCs, which probably represent the cells primarily involved in the ‘psoriatic march’.

Source: onlinelibrary.wiley.com

Obese patients with psoriatic arthritis demonstrate a worse response when starting anti–tumor necrosis factor therapy than do normal weight patients, but achievement of minimal disease activity can be improved by weight loss, based on two studies by Dr. Giovanni Di Minno, lead investigator on both.

The first study investigated the influence of obesity and the second, the influence of weight loss on response to starting anti–tumor necrosis factor (TNF) therapy.

The study on the effect of obesity on response to anti-TNF therapy in psoriatic arthritis (PsA) involved 135 psoriatic arthritis patients with a body mass index (BMI) over 30 kg/m2and 135 normal weight controls. Dr. Di Minno and his coinvestigators found that the two groups did not differ significantly in terms of disease activity and vascular risk factors including swollen and tender joint counts, levels of C-reactive protein, erythrocyte sedimentation rates, and psoriasis area severity index scores. They found that patients with a BMI over 30 had a higher prevalence of hypercholesterolemia and hypertriglyceridemia.

Dr. Di Minno and his associates in the department of clinical and experimental medicine, Federico II University, Naples, Italy, found that at 12 months’ follow-up, 98 of the 270 patients (36.3%) had achieved minimal disease activity (MDA). The prevalence of obesity was higher in those not achieving MDA than in those achieving it (64% vs. 25.5%, P less than .001).

"A BMI of over 30 was shown to be a strong predictor [of not achieving MDA] with a hazard ratio of 4.90 (95%CI: 3.04-7.87; P less than .001)," according to Cox regression analysis findings, reported Dr. Di Minno.

At 24 months, 17.3% of those who achieved MDA a year earlier relapsed, and 82.7% maintained their MDA. "A BMI greater than 30 was associated with a higher risk of disease relapse, with a hazard ratio of 2.04 [95% CI: 1.02-3.61; P = .014]," he said at the annual European Congress of Rheumatology.

Dr. Di Minno also noted that there was no difference found between the three anti-TNF blockers (infliximab, etanercept, and adalimumab) used in the study.

Session moderator Dr. Laura Coates said that the study was valuable because patients with PsA were prone to being overweight, and there was an established link between excess weight, metabolic syndrome, and psoriasis. "Until this study, there were no data to support the concept that weight loss could alter people’s outcome in terms of their arthritis response.

"This provides evidence of an immediate improvement to people’s health with weight loss, in terms of a better response to the anti-TNF therapies," said Dr. Coates of the division of rheumatic and musculoskeletal disease at Chapel Allerton Hospital in Leeds, England.

Furthermore, Dr. Coates noted that there was also a known association between psoriasis/PsA and cardiovascular morbidity related to the metabolic syndrome. "Controlling weight is very important for these patients in the long term as well," she said.

Introducing his second study, which investigated the effect of weight loss in obese patients, Dr Di Minno noted that prior studies had shown that restricting calorie intake reduced obesity-related inflammation.

The study specifically investigated the impact of changes in body weight on the achievement of MDA in PsA patients starting treatment on anti-TNF therapy.

A total of 126 obese (BMI greater than 30) patients with active PsA, who had not responded to traditional disease-modifying antirheumaic drugs were randomized to either a diet of 1,300 calories per day (n = 63), or an unrestricted diet (n = 63), with the advice to eat more vegetables, fish, and fresh fruits and no more than 2 tablespoons of olive oil per day. All patients were encouraged to exercise five times a week, and all started on anti-TNF therapy immediately.

"The intervention diet was the traditional Mediterranean diet rich in fibers, with a careful balance of sugar, proteins, and lipids, similar to the diet used by diabetics," explained Dr. Di Minno. The Mediterranean diet has been shown to lessen inflammation because it is rich in mono- and polyunsaturated fatty acids, antioxidants, dietary fiber, and phytochemicals.

At the 6-month follow-up, the researchers found a 5%-10% weight loss was achieved by 47.6% of patients on the hypocaloric diet versus 28.6% on the unrestricted diet. Only 41.3% of patients on the hypocaloric diet lost more than 10% of their body weight.

Furthermore, patients on the hypocaloric diet had more significant reductions in triglycerides and cholesterol compared with those on the unrestricted diet (29.1% vs. 10% for triglycerides. and 23.7% vs. 8.1% for cholesterol, for hypocaloric and unrestricted diets, respectively).

"To our surprise we found that the Mediterranean diet was not much better than the other diet in terms of MDA achievement [42.9% on the hypocaloric diet vs. 34.9% on the free diet; P = .465]," reported Dr. Di Minno.

MDA was achieved more frequently by patients who achieved a greater than 5% weight loss compared with those who did not [50% vs. 23.1%]. Furthermore, as weight loss increased so did the achievement of MDA, with 16.7%, 42.9%, and 59.5% MDA achievement for a weight loss of less than 5%, 5%-10%, and more than 10%, respectively.

The data strongly support the need for the control of body weight and cardiometabolic parameters in PsA subjects starting anti-TNF treatment, Dr. Di Minno said. "This may result in a better achievement of minimal disease activity in these patients."

Source: skinandallergynews.com

The Food and Drug Administration USA has issued a warning letter to The Himalayan Institute, Buffalo, New York. after an inspection of their liquid dietary supplement manufacturing facility. The letter also mentions their Himalayan Triphala Oil webpage which states “Ayuredic practitioners have traditionally used ‘medicated’ or treated oils topically to assist with conditions such as . . . eczema, psoriasis, and dermatitis . . . .”

Here is a copy of the letter:

Quote:

---

Mr. Rolf Sovik, President
Himalayan Institute of Buffalo
841 Delaware Avenue
Buffalo, New York 14209

Dear Mr. Sovik:

The U.S. Food and Drug Administration (FDA) conducted an inspection of your liquid dietary supplement manufacturing facility, located at 952 Bethany Turnpike, Honesdale, PA, from January 4, 2012 through January 18, 2012. The inspection found that your facility has serious violations of the Current Good Manufacturing Practice (CGMP) regulations for dietary supplements, Title 21, Code of Federal Regulations (CFR), Part 111 (21 CFR Part 111).  These violations cause your dietary supplement products identified below to be adulterated within the meaning of section 402(g)(1) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 342(g)(1)] in that the products have been prepared, packed, or held under conditions that do not meet CGMP requirements for dietary supplements.

In addition, we have reviewed the labeling for your products and your website at [web]www.himalayaninstitute.org.[/web] Based on our review, we have concluded that your products identified below are in violation of sections 403, 505(a), and/or 502(f)(1) of the Act [21 U.S.C. §§ 343, 355(a), and/or 352(f)(1)] and the regulations implementing the food labeling requirements of the Act, which are found in Title 21, Code of Federal Regulations, Part 101 (21 CFR 101). You may find the Act and FDA regulations through links on FDA’s home page at [web]www.fda.gov.[/web]

Dietary Supplement CGMP Violations

1)    You have not prepared and followed a written master manufacturing record (MMR) for each batch size of dietary supplement that you manufacture, to ensure uniformity in the finished batch from batch to batch, as required by 21 CFR 111.205(a). Specifically,


    You use blank “Formulations Logs” that contain pre-determined multiplication factors for each ingredient used in a particular product as your MMR. Before a new batch of product is manufactured, employees use this multiplication factor to determine the amounts of each ingredient that must be used based on the total batch volume that is needed. These amounts are then handwritten on the “Formulation Log.” Our review of each MMR for your products Elixir 29, Immuno-Stim, Sweet Dreams, Safe Travel, and Sages Treasure revealed that the same MMR was used for multiple batch sizes.
    You did not follow the MMRs for the following batches of product:


i)    Elixir 29 Lot # (b)(4) and (b)(4)-You substituted (b)(4) for blue vervain leaf. You used many spagyric ingredients in place of herbal extracts. A 2 oz. bottle of product contains 59 ml instead of the prescribed 60 ml.

ii)    Sweet Dreams Lot # (b)(4)-You substituted (b)(4) and (b)(4) for skullcap herb.  You used many spagyric ingredients in place of herbal extracts. A 2 oz. bottle of product contains 59 ml instead of the prescribed 60 ml.

iii)    Safe Travel Lot # (b)(4)-You substituted (b)(4) for goldenseal root. You used many spagyric ingredients in place of herbal extracts. A 2 oz. bottle of product contains 59 ml instead of the prescribed 60 ml.

iv)    Safe Travel Lot # (b)(4)- You added extra licorice and calamus to make up for a shortage in wood betony herb. You used many spagyric ingredients in place of herbal extracts.

2)    You failed to conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, as required by 21 CFR 111.75(a)(1)(i). Specifically, you verbally confirmed to our investigator that you did not test or verify the identities of any dietary ingredients used in the following batches of product:


    Elixir 29 - Lot #: (b)(4)
    Immuno-Stim – Lot #: (b)(4)
    Sweet Dreams – Lot #: (b)(4)
    Safe Travel – Lot #: (b)(4)
    Sages Treasure – Lot #: (b)(4)


Before using a component that is a dietary ingredient, you must conduct at least one appropriate test or examination to verify the identity of any component that is a dietary ingredient, unless you petition FDA under 21 CFR 111.75(a)(1)(ii) and FDA exempts you from such testing. Your firm has not petitioned FDA for such an exemption.

3)    Your firm failed to qualify a supplier of a component by establishing the reliability of the supplier’s certificate of analysis (COA) through confirmation of the results of their tests or examinations, as required by 21 CFR 111.75(a)(2)(ii)(A). Your firm verbally confirmed that you did not establish the reliability of your suppliers’ certificates of analysis.

While you must conduct, at minimum, one test or examination to verify the identity of any component that is a dietary ingredient, you may, if desired, rely on a COA for other specifications for those ingredients, and to confirm the identity of other components that are not dietary ingredients. However, you may only rely on a COA if you have met the requirements of 21 CFR 111.75(a)(2)(ii), which include qualifying the supplier.

4)    You failed to establish specifications for any of your dietary supplement products, such as Elixir 29, Immuno-Stim, Sweet Dreams, Safe Travel, and Sages Treasure, as required by 21 CFR 111.70. Specifically:


    You failed to establish specifications for any point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the MMR, as required by 21 CFR 111.70(a).
    You failed to establish component specifications, as required by 21 CFR 111.70(b).
    You failed to establish specifications for dietary supplement labels (label specifications) and for packaging that may come in contact with dietary supplements (packaging specifications) as required by 21 CFR 111.70(d).
    You failed to establish product specifications for the identity, purity, strength, and composition of the finished batch of each dietary supplement that you manufacture, and for limits on those types of contamination that may adulterate, or that may lead to the adulteration of, the finished batch, as required by 21 CFR 111.70(e).


We also note that once you have established the above specifications, you must determine whether the specifications have been met, as required by 21 CFR 111.73.

5)    You failed to quarantine components before you used them in the manufacture of a dietary supplement, as required by 21 CFR 111.155©. For example, the dietary supplement components used to manufacture the finished batches noted in item no. 2 above, were used without being quarantined. Your firm verbally confirmed to our investigator, that you do not quarantine components before they are used in the manufacturing of a dietary supplement. Prior to using components in the manufacture of a dietary supplement, you must quarantine the components until all of the requirements of 21 CFR 111.155©(1), ©(2), and ©(3) have been met.

6)    You failed to include required information in your MMRs for your Elixir 29, Immuno-Stim, Sweet Dreams, Safe Travel, and Sages Treasure products, as required by 21 CFR 111.210. Specifically:


    Your MMR must include the identity and weight or measure of each dietary ingredient that will be declared on the Supplement Facts label and the identity of each ingredient that will be declared on the ingredients list of the dietary supplement [21 CFR 111.210(d)]. However, your MMRs do not contain water and the weight or measure of grain alcohol although they are declared on the labels for these products.
    Your MMR must include a statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process where control is needed to ensure the quality of the dietary supplement, and the expected yield when you finish manufacturing the dietary supplement, including the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary and material review is conducted and disposition decision is made [21 CFR 111.210(f)]. However, your MMRs for these products do not include this information.
    Your MMR must include a description of packaging and a representative label, or a cross-reference to the physical location of the actual or representative label [21 CFR 111.210(g)]. However, your MMRs for these products do not contain this.
    Your MMR must include written instructions, including the following: specifications for each point, step, or stage in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the MMR; procedures for sampling and a cross-reference to procedures for tests or examinations; specific actions necessary to perform and verify points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the MMR; and, corrective action plans for use when a specification is not met [21 CFR 111.210(h)(1)-(3),(5)]. However, your MMRs for these products do not include this information.


7)    You failed to include required information in your batch production records (BPRs) for your Elixir 29 (Lot #: (b)(4)), Immuno-Stim (Lot #: (b)(4)), Sweet Dreams (Lot #: (b)(4)), Safe Travel (Lot #: (b)(4)), and Sages Treasure (Lot #: (b)(4)) products, as required by 21 CFR 111.260. Specifically:


    Your BPR must include the identity of the equipment and processing lines used in producing the batch [21 CFR 111.260(b)].  However, your BPRs for these products do not include this information.
    Your BPR must include the date and time of the maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch, or a cross-reference to records, such as individual equipment logs, where this information is retained [21 CFR 111.260©]. However, your BPRs for these products do not include this information.
    Your BPR must include the identity and weight or measure of each component used [21 CFR 111.260(e)]. However, the BPRs for these products do not include water, which is declared on your product labels.
    Your BPR must include a statement of the actual yield and a statement of the percentage of theoretical yield at appropriate phases of processing [21 CFR 111.260(f)]. However, your BPRs for these products lack this information.
    Your BPR must include documentation that the finished dietary supplement meets specifications established in accordance with 21 CFR 111.70(e) and (g) [21 CFR 111.260(i)]. However, your BPRs for these products lack this information. As is discussed above in item no. 4, you have not established any specifications for these dietary supplement products.
    Your BPR must include documentation, at the time of performance, of the manufacture of the batch, including the initials of the person responsible for weighing or measuring each component used in the batch, the initials of the person responsible for verifying the weight or measure of each component used in the batch, the initials of the person responsible for adding the component to the batch, and the initials of the person responsible for verifying the addition of components to the batch [21 CFR 111.260(j)(2)]. However, your BPRs for these products do not include any of this information.
    Your BPR must include documentation, at the time of performance, of packaging and labeling operations including the unique identifier that you assigned to packaging and labels used, the quantity of the packaging and labels used, and, when label reconciliation is required, reconciliation of any discrepancies between issuance and use of labels; an actual or representative label, or a cross-reference to the physical location of the actual or representative label specified in the MMR; and the results of any tests or examinations conducted on packaged and labeled dietary supplements (including repackaged or relabeled dietary supplements), or a cross-reference to the physical location of such results [21 CFR 111.260(k)]. However, your BPRs for these products do not include this information.
    Your BPR must include documentation at the time of performance that quality control personnel reviewed the BPR; approved or rejected any reprocessing or repackaging; approved and released, or rejected, the batch for distribution, including any reprocessed batch; and approved and released, or rejected, the packaged and labeled dietary supplement, including any repackaged or relabeled dietary supplement [21 CFR 111.260(l)]. However, your BPRs for these products do not include this information. Your BPRs for these products do not include any documentation of review by quality control personnel.
    Your BPR must include documentation at the time of performance of any required material review and disposition decision [21 CFR 111.260(m)]. However, several of your BPRs, for example, Elixir 29 Lot #(b)(4), Sweet Dreams Lot #(b)(4), and Safe Travel Lot #(b)(4), show deviations from the MMR in that ingredients other than the ones specified are used, but there is no documentation that you conducted a material review or made a disposition decision. As required by 21 CFR 111.113(a)(2), quality control personnel must conduct a material review and make a disposition decision if a batch deviates from the MMR, including when any step established in the MMR is not completed and including any deviation from specifications.


8)    You failed to establish and follow written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision, and for approving or rejecting any reprocessing, as required by 21 CFR 111.103. Specifically, your firm verbally confirmed to our investigator, that no written procedures exist at your facility for the responsibilities of the quality control operations.

9)    You firm failed to make and keep records of written procedures for laboratory operations, including written procedures for the tests and examinations that you conduct to determine whether specifications are met, as required by 21 CFR 111.325(b)(1). Specifically, your firm verbally confirmed to our investigator that you did not have written procedures for laboratory operations and were not aware that these procedures had to be written.

10)    You failed to establish written procedures to fulfill the requirements of 21 CFR 111.560 relating to the review and investigation of product complaints, as required by 21 CFR 111.553. Specifically, your firm verbally confirmed to our investigator that there is no formal system in place to address product complaints.

11)    You failed to establish and follow written procedures to fulfill the requirements of 21 CFR Part 111, Subpart N for handling returned dietary supplements, as required by 21 CFR 111.503. Specifically, you have not established written procedures to ensure the proper disposition of returned dietary supplements. Additionally, your firm verbally confirmed to our investigator that products were returned to your facility and that there were no records available which document the final disposition of these returned dietary supplements as required by 21 CFR 111.535(b)(2).   

12)    You failed to routinely calibrate, inspect, or check the automated, mechanical, or electronic equipment that you use to manufacture, package, label, or hold a dietary supplement, to ensure proper performance, as required by 21 CFR 111.30©. Specifically, your firm verbally confirmed to our investigator, that the equipment noted below was used to manufacture dietary supplements and was not calibrated:


    The scale, manufactured by (b)(4), which is used to weigh all herbal ingredients; and
    The specific gravity meter which is used to measure fine % alcohol concentration in the finished products.


13)    You failed to make and keep records of your written procedures for calibrating, inspecting, and checking automated, mechanical, and electronic equipment; and maintaining, cleaning, and sanitizing, as necessary, all equipment, utensils, and any other contact surfaces that are used to manufacture, package, label, or hold components or dietary supplements, as required by 21 CFR 111.35(b)(1)(ii) and (iii). You also failed to make and keep written records of calibrations, inspections, and checks of automated, mechanical, and electronic equipment, as required by 21 CFR 111.35(b)(4). Specifically:


    You verbally informed our investigator that the UV Water System, manufactured by (b)(4) was inspected by your firm (b)(4); however, you stated that there are no written procedures for this inspection, nor do you maintain any records of these inspections.
    You verbally informed our investigator that there are no written procedures in place that outline the cleaning process for the lab/processing area and equipment.


Unapproved New Drugs:

Your product labels and website, [web]www.himalayaninstitute.org,[/web] promote your products for conditions that cause the products identified below to be drugs under section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)]. The therapeutic claims on your product labels and website establish that these products are drugs because they are intended for use in the cure, mitigation, treatment, or prevention of disease. Examples of the claims found on your product labels and website include:

Inflam-away label


    The name of your product implies that your product reduces inflammation


Himalayan Triphala Oil webpage:


    “Ayuredic practitioners have traditionally used ‘medicated’ or treated oils topically to assist with conditions such as . . . eczema, psoriasis, and dermatitis . . . .”
    “Sesame oil [ingredient in the product] . . . is considered to be effective in treating the pain and swelling of rheumatoid arthritis . . . .”
    “Due to this lecithin content it is believed to . . . alleviate . . . depression . . . .”
    “It may also be used as a mouthwash (called oil pulling) for problem gums and inflammation.”


Namastea Black webpage


    “[B]lack tea may protect against certain types of heart disease while having a favorable influence on blood lipid levels.”
    “[T]hese compound [antioxidants] are helpful in supporting the body’s immune function in preventing cancer . . . .”


Your products are not generally recognized as safe and effective for the above referenced uses and, therefore, the products are “new drugs” under section 201(p) of the Act [21 U.S.C. § 321(p)].  A new drug may not be legally marketed in the United States without prior approval from FDA as described in section 505(a) of the Act [21 U.S.C. § 355(a)]. FDA approves a new drug on the basis of scientific data submitted by a drug sponsor to demonstrate that the drug is safe and effective.

Further, your Himalayan Triphala Oil and Namastea Black products are offered for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layperson can use these products safely for their intended uses. Thus, the labeling fails to bear adequate directions for the products’ intended uses, causing the products to be misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)]. The introduction of misbranded drugs into interstate commerce is a violation of section 301(a) of the Act [21 U.S.C. § 331(a)].

Misbranded Food

Under section 403®(1)(A) of the Act [21 U.S.C. § 343®(1)(A)], a claim made in the label or labeling of a food that characterizes the level of any nutrient which is of the type required to be in the label or labeling of the food (a “nutrient content claim”) must be made in accordance with regulations promulgated by the Secretary (or, by delegation, FDA). The use of a term, not defined by regulation, in food labeling to characterize the level of a nutrient misbrands a product under section 403®(2)(A)(i) of the Act [21 U.S.C. § 343®(2)(A)(i)].

Nutrient content claims that characterize the level of antioxidant nutrients present in a food must also comply with the specific requirements listed in 21 CFR 101.54(g). These requirements state, in part, that for a product to bear such a claim, an RDI must have been established for each of the nutrients that are the subject of the claim (21 CFR 101.54(g)(1)), and these nutrients must have recognized antioxidant activity (21 CFR 101.54(g)(2)). The level of each nutrient that is the subject of the claim must also be sufficient to qualify for the claim under 21 CFR 101.54(b), ©, or (e) (21 CFR 101.54(g)(3)). For example, to bear the claim "high in antioxidant vitamin C," the product must contain 20 percent or more of the RDI for vitamin C. Such a claim must also include the names of the nutrients that are the subject of the claim as part of the claim or, alternatively, the term "antioxidant" or "antioxidants" when used as part of a nutrient content claim such as “high in antioxidants” may be linked by a symbol (e.g., an asterisk) that refers to the same symbol that appears elsewhere on the same panel of the product label, followed by the name or names of the nutrients with recognized antioxidant activity (21 CFR 101.54(g)(4)). The use of a nutrient content claim that uses the term "antioxidant" but does not comply with the requirements of 21 CFR 101.54(g) misbrands a product under section 403®(1)(A) of the Act.

Your webpage entitled "Namastea Black (225g Bag)" at [web]www.himalayaninstitute.org[/web] includes the claims, "Black tea is recognized for its rich concentration in antioxidant polyphenols such as EGC, EGCG, and other flavonols . . . .”  and “Loaded with protective antioxidant polyphenols.” The terms "rich concentration” and “[l]oaded with” characterize the level of antioxidant nutrients in the product and, therefore, these claims are nutrient content claims (see section 403®(1)(A) of the Act and 21 CFR 101.13(b)). Even if we determined that the terms "rich concentration" or “[l]oaded with” could be considered synonyms for terms defined by regulation (e.g., "high" or "good source"), nutrient content claims that use the term "antioxidant" must meet the requirements of 21 CFR 101.54(g). These claims do not comply with 21 CFR 101.54(g)(1) because no RDI has been established for polyphenols, EGC, EGCG, or flavonols. Thus, these unauthorized nutrient content claims cause your product to be misbranded under section 403®(1)(A) of the Act.

Your Adapt-a-gem product is misbranded within the meaning of section 403(u) of the Act [21 U.S.C. 343(u)] in that it is represented as containing ginseng, but the purported ginseng ingredient is not from a plant classified within the genus Panax. The ingredient statement for your product lists Siberian Ginseng (Eleutherococcus senticosus). Section 10806(b)(1) of the Farm Security and Rural Investment Act of 2002 (Pub. L. 107-171) provides that the term "ginseng" may only be considered to be a common or usual name (or part thereof) for any herb or herbal ingredient derived from a plant classified within the genus Panax. Therefore, Eleutherococcus senticosus may not be declared under a name that includes the term "ginseng."

Your Adapt-a-gem and Cholesta-low products are misbranded within the meaning of section 403(q)(5)(F) of the Act [21 U.S.C. § 343(q)(5)(F)] in that the label fails to bear nutrition labeling (“Supplement Facts” panel) as required by 21 CFR 101.36. In addition, should you decide to change the name of your Inflam-away product so that it no longer promotes it as an unapproved new drug, as stated on page seven (7) of this letter, it  would then become a misbranded dietary supplement within the meaning of section 403(q)(5)(F) of the Act [21 U.S.C. § 343(q)(5)(F)], in that the label fails to bear nutrition labeling (“Supplement Facts” panel) as required by 21 CFR 101.36.

Your Cholesta-low product is misbranded within the meaning of section 403(i)(2) of the Act [21 U.S.C. § 343(i)(2] in that the ingredients statement does not list the ingredient He Shou Wu root by the common or usual name. In accordance with 21 CFR 101.4(h), the common or usual name of ingredients of dietary supplements that are botanicals shall be consistent with the names standardized in Herbs of Commerce, 1992 edition. The common name for He Shou Wu in Herbs of Commerce is Fo-Ti.

The above violations are not intended to be an all-inclusive list of violations at your facility and with your products, labels, and labeling. It is your responsibility to ensure that your products are in compliance with all applicable statutes and regulations, including the Act, the CGMP regulations for dietary supplements, and FDA’s food labeling regulations.

You should take prompt action to correct the violations described in this letter. Failure to take appropriate corrective action may result in FDA taking regulatory action without further notice, such as injunction or seizure.

Further, Section 743 of the Act [21 U.S.C. 379j-31] authorizes FDA to assess and collect fees to cover FDA’s costs for certain activities, including reinspection-related costs. A reinspection is one or more inspections conducted subsequent to an inspection that identified noncompliance materially related to a food safety requirement of the Act, specifically to determine whether compliance has been achieved. Reinspection-related costs means all expenses, including administrative expenses, incurred in connection with FDA’s arranging, conducting, and evaluating the results of the reinspection and assessing and collecting the reinspection fees [21 U.S.C. 379j-31(a)(2)(B)]. For a domestic facility, FDA will assess and collect fees for reinspection-related costs from the responsible party for the domestic facility.  The inspection noted in this letter identified noncompliance materially related to a food safety requirement of the Act. Accordingly, FDA may assess fees to cover any reinspection-related costs.

In addition to the above violations, we also have the following concerns:


    You were unable to provide any documentation to indicate that you have performed training of your personnel. Our investigator was informed that most of the training is done on-the-job; however the firm does not document this training. Under 21 CFR 111.14(b)(2), you must make and keep documentation of training, including the date of the training, the type of training, and the person(s) trained.
    You have not formally identified personnel to be responsible for your quality control operations. Specifically, you verbally confirmed to our investigator that while there is an employee who has been informally filling the role of quality control, no one has been formally designated for this position. Under 21 CFR 111.12(b), you must identify who is responsible for your quality control operations. Each person who is identified to perform quality control operations must be qualified to do so and have distinct and separate responsibilities related to performing such operations from those responsibilities that the person otherwise has when not performing such operations.
    As noted above, your batch production records indicate several instances where ingredients listed in the master manufacturing records were replaced with other ingredients. Under section 403(s)(2)(A)(i) of the Act [21 U.S.C. §343(s)(2)(A)(i)], a dietary supplement is misbranded if its label or labeling fails to list the name of each ingredient of the supplement that is described in section 321(ff) of the Act [21 U.S.C. § 201(ff)]. 


You should notify this office in writing within fifteen (15) working days from your receipt of this letter of the specific steps that you have taken to correct the violations listed in this letter and to prevent their recurrence. Your response should include documentation of the corrective actions that you have taken or that you plan to take to correct these violations, including the specifics of what methods and controls you have implemented or plan to implement to prevent the recurrence of the violations. If corrective actions cannot be completed within fifteen (15) working days of receiving this letter, please state the reason for the delay and include a timetable for the implementation of the remaining corrections.

A new treatment being developed for bowel disease could also help relieve the suffering of arthritis patients, experts believe.

The as yet unnamed drug will become the first to be tested at Wales’ only arthritis treatment research centre – called CREATE – which has been designed to develop new treatments to stop inflammatory arthritis.

Based at Cardiff University’s School of Medicine, the first trial is expected to involve about 50 patients from across South Wales.

Professor Ernest Choy, professor of rheumatology at Cardiff University, said: “The aim is to develop novel and more effective treatments for patients with inflammatory arthritis.

“Unlike the more common forms like osteoarthritis, patients with these forms of inflammatory arthritis – rheumatoid and psoriatic arthritis – have much higher rates of mortality because the inflammation can spread through the body.

“As a result they have more complicated and severe disease and survival rates subsequently decrease compared to the general population.

“These are aggressive conditions and we know that a key factor in improving outcomes is to keep the inflammation to a minimum.

“Over the last 20 years there have been some new and effective treatments which have improved the condition significantly.

“But the number of patients who get to persistent remission remains low – at less than 30%. Our aim is to try and develop new treatments which are more effective and put more patients into remission.”

The new centre – the Arthritis Research UK Experimental Arthritis Treatment Centre (Create) – which has been backed with £115,000 of start-up funding from Arthritis Research UK over the next three years and additional funding from National Institute for Social Care and Health Research (NISCHR) and Cardiff University, will also develop new laboratory tests that will determine the most appropriate therapies for individual patients.

One of the first pieces of work for the new centre will be to examine whether a new and unlicensed treatment for inflammatory bowel disease will also be effective for patients with rheumatoid and psoriatic arthritis – experts are hopeful the treatment will be effective in addressing the inflammatory response and symptoms in arthritic patients.

Prof Choy added: “For the last few years, the opportunity for patients in Wales to get access to innovative treatments has been rather limited. Having this centre will open up the opportunities for better treatment.

“And it will also allow us to look across the horizon and see whether there are treatment examples from other diseases that could help arthritis.”

Source: walesonline

Thank you for welcoming me Fred. I found this site while browsing on the web for someone to publish what I had written. I decided to write down how Psoriasis had and still has made me a very insecure person and just wanted to let others know that the old saying "Ignorance is Bliss" is wrong. I only wrote a couple of pages but it just summed up how little matters had affected me and wanted others to know that they are not alone. Susan x

G'day guys I'm new to this forum I've had psoriasis since I was 18 I'm 35 now it's been on and off but at he moment it's the worst it's ever been so Im intersted if there is any new treatment my doc wants to try mega iv dose's of vitamin c and zinc , has any one tried this

A new study suggests that people with psoriasis are also likely to have one other autoimmune disease, with rheumatoid arthritis coming out top.

Background:
Previous studies provide evidence that there is a greater frequency of autoimmune diseases among patients with psoriasis than in the general population.

Objective:
This study examined the association between psoriasis and 21 common autoimmune diseases.

Methods:
A retrospective cohort study was conducted among persons who were members of Kaiser Permanente Southern California from 2004 to 2011. A total of 25,341 patients with 2 or more diagnosis codes for any psoriatic disease were evaluated. Five persons not meeting this case definition were matched to each psoriatic patient based on age, sex, and length of enrollment.

Results:
Patients with psoriasis were more likely to have at least 1 other autoimmune disease (odds ratio [OR] 1.6; 95% confidence interval [CI] 1.5-1.7) and to have at least 2 other autoimmune diseases (1.9; 95% CI 1.6-2.4). Of the 17 conditions evaluated, associations with 14 were found to be statistically significant. The strongest association was with rheumatoid arthritis (3.6; 95% CI 3.4-3.9).

Limitations:
Patients with autoimmune conditions are likely to have a greater number of health care encounters, which may result in overascertainment and misascertainment of immune-mediated conditions, although the patients included in the study averaged 5.2 years of observation and the comparison subjects were matched on length of enrolment.

Conclusions:
The study suggests a genetic or environmental cause common across autoimmune diseases. Further investigation of individuals with multiple autoimmune diseases may yield important clues about the origin and pathogenesis of the disease.

Source: eblue.org

Eli Lilly and Company announced the presentation of 12-week results from a Phase IIb study of baricitinib, formerly LY3009104 (INCB28050), an orally available janus kinase (JAK) inhibitor, in patients with active rheumatoid arthritis (RA). The results were presented as a late-breaking oral presentation at the European League Against Rheumatism's (EULAR) Annual European Congress of Rheumatology [EULAR abstract LB0005: 12-Week Results of a Phase IIb Dose-Ranging Study of LY3009104 (INCB028050), an Oral JAK1/JAK2 Inhibitor, in Combination with Traditional DMARDs in Patients with Rheumatoid Arthritis].

The Phase IIb randomized double-blind, placebo-controlled, dose-ranging study, known as JADA, involved a total of 301 patients with active RA on stable doses of methotrexate. Patients were randomized to receive either placebo or one of four once-daily doses of baricitinib (1 mg, 2 mg, 4 mg or 8 mg) for 12 weeks.

Primary Endpoint Achieved:
The Phase IIb trial achieved the primary endpoint by demonstrating a statistically significant difference in the American College of Rheumatology 20 (ACR20) response between the combined 4 mg and 8 mg baricitinib groups (76 percent) compared with placebo (41 percent) after 12 weeks of treatment (p < 0.001). Statistically significant improvement was observed at the first assessment point after two weeks of treatment and was sustained through week 12.

Summary of Secondary Endpoints:
A statistically significant difference in response for the ACR20, ACR50 and ACR70 secondary endpoints was observed with the 1 mg, 4 mg and 8 mg dose groups compared with placebo.

ACR20

    8 mg: 78 percent (p < 0.001)
    4 mg: 75 percent (p < 0.001)
    2 mg: 54 percent (not significant)
    1 mg: 57 percent (p < 0.05)
    Placebo: 41 percent

ACR50

    8 mg: 40 percent (p < 0.001)
    4 mg: 35 percent (p < 0.001)
    2 mg: 17 percent (not significant)
    1 mg: 31 percent (p < 0.05)
    Placebo: 10 percent

ACR70

    8 mg: 20 percent (p < 0.001)
    4 mg: 23 percent (p < 0.001)
    2 mg: 8 percent (not significant)
    1 mg: 12 percent (p < 0.05)
    Placebo: 2 percent

Safety Results:
The most common treatment-emergent adverse event class was infections, with a similar rate observed among patients in the placebo group (12 percent) and patients receiving baricitinib (14 percent). One patient in the placebo group was diagnosed with an opportunistic infection of toxocariasis. No deaths or opportunistic infections occurred in the active treatment groups.

There were seven serious adverse events reported in six patients (two events in the placebo group, four in the 2 mg group and one in the 8 mg group). Dose-dependent changes in laboratory tests (hemoglobin, neutrophil, serum creatinine, LDL and HDL) were observed, with greater changes being observed in the 8 mg baricitinib group.

Trial Design and Status:
This Phase IIb trial consists of three parts: Part A, Part B and an open-label extension. Part A was randomized, double-blind and placebo-controlled. Patients randomized to baricitinib received one of four doses administered once daily for 12 weeks.

In Part B, patients initially randomized to placebo or the 1 mg baricitinib dose were re-randomized to receive either 4 mg once daily or 2 mg twice daily for 12 weeks. Patients initially randomized to the 2 mg, 4 mg and 8 mg doses continued therapy for an additional 12 weeks.

Patients completing Part B were eligible to continue in an open-label extension arm on either the 4 mg or 8 mg once daily doses of baricitinib for 52 additional weeks.

Part B of the study has completed and data analysis is underway. Patients are continuing to participate in the open-label long-term extension of the trial.

About Baricitinib:
Baricitinib is an orally administered selective JAK1 and JAK2 inhibitor that is JAK3-sparing. Currently, baricitinib is in Phase II development as a treatment for rheumatoid arthritis and psoriasis.

Source: lilly.com

According to a study presented today at EULAR 2012, the Annual Congress of the European League Against Rheumatism, patients with psoriatic arthritis (PsA) who are starting anti-tumour necrosis factor (anti-TNF) treatment and adhere to a hypocaloric diet have a significantly greater chance of achieving minimal disease activity (MDA, an important measure of disease activity) at six months compared to those on a standard diet.

The results of an Italian study of 138 obese PsA patients demonstrated that those who achieved a ≥10% weight loss following a calorie restricted diet, were more likely to achieve MDA, compared to patients on a standard diet (p=0.001). These patients also had significantly higher changes in erythrocyte sedimentation rate (ESR, a test that indirectly measures the amount of inflammation in the body), and c-reactive protein (CRP, a marker of systemic inflammation, a recently identified predictor of structural damage progression) compared to patients on a standard diet.

"A study presented at the 2009 meeting of the Society for Investigative Dermatology, alerted us to the fact that patients with psoriatic arthritis have an increased prevalence of obesity, however our study has gone beyond that, assessing whether diet is able to improve the achievement of minimal disease activity in obese patients treated with anti-TNFs" said Dr. Dario Di Minno from the University of Naples Federico II, Italy and lead author of the study. "The results of our study suggest that obese patients with psoriatic arthritis who stick to a hypocaloric diet have a greater chance of achieving treatment goals."

The study demonstrated that a hypocaloric diet is a predictor of MDA achievement (hazard ratio HR: 4.79; p=0.002) after six months of treatment with anti-TNFs in patients as compared to those on a standard diet. Of the 138 obese subjects with PsA, 69 received a hypocaloric diet and 69 a self-managed diet. At baseline and at six months follow-up, patients underwent a complete clinical rheumatologic and laboratory evaluation.

In a separate PsA study by the same authors, 135 obese and 135 matched normal-weighted patients (controls) with active disease starting treatment with anti-TNFs were followed for 24 months to evaluate whether the presence of obesity impacts the achievement of MDA. Of the 270 subjects, 36.3% achieved MDA and the prevalence of obesity was higher in those not achieving MDA than in those achieving it (64.0% versus 25.5%, p<0.001). After adjusting for all the other variables, obesity was associated with a higher risk of not achieving MDA (HR: 4.90, 95%, CI: 3.04-7.87, p<0.001). Among the 98 subjects that had achieved MDA at the 12 month follow-up, the presence of obesity was associated with a poor probability of maintaining MDA at 24 month follow-up (HR:2.04, 95%CI:1.015-3.61, p=0.014).

Source: sciencecodex.com

Results from the RAPID™-PsA study presented this week at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology in Germany showed that certolizumab pegol (Cimzia) compared to placebo improved the signs and symptoms of arthritis in adult patients with active psoriatic arthritis (PsA).

“Certolizumab pegol has been shown to be clinically effective in moderate to severe rheumatoid arthritis. The RAPID™-PsA study is the first controlled study to assess the efficacy and safety of certolizumab pegol in adult patients with psoriatic arthritis,” said Dr Philip J Mease, Director Rheumatology Research, Swedish Medical Center and University of Washington School of Medicine, Seattle, WA, USA. “Results from the study showed that certolizumab pegol improved the signs and symptoms of psoriatic arthritis when compared to placebo.”

The RAPID™-PsA study randomized 409 patients with established psoriatic arthritis to receive either certolizumab pegol 200 mg every 2 weeks or 400 mg every 4 weeks or placebo. In the certolizumab pegol arms, patients received a loading dose of 400 mg certolizumab pegol at weeks 0, 2 and 4. Patients enrolled in this study must have failed at least one disease-modifying anti-rheumatic drug (DMARD) and could have received a maximum of one anti-TNF (tumour necrosis factor). At baseline, 20% of patients had previously failed one anti-TNF. Within the placebo arm, patients who failed to achieve a >10% decrease in tender joint count and swollen joint count at weeks 14 and 16 were re-randomized at week 16 to receive certolizumab pegol 200 mg every 2 weeks or 400 mg every 4 weeks following the loading dose.1

The primary endpoints of the study were the ACR20 response at week 12 and the modified total sharp score (mTSS) at week 24*. At week 12, the ACR20 response was significantly higher in both certolizumab pegol arms versus placebo (58.0%, 51.9%, vs 24.3% in 200 mg, 400 mg and placebo respectively, p<0.001). Within the certolizumab pegol arms, a greater ACR20 response versus placebo was achieved at week 1 (21.0%, 23.0% vs 7.4% in 200 mg, 400 mg and placebo respectively).1

The most common adverse events with >5% incidence in the combined certolizumab pegol or placebo group were nasopharyngitis and upper respiratory tract infections. The most common serious adverse events with >1% incidence in the combined certolizumab pegol or placebo group were infections and infestations.2

In the European Union, certolizumab pegol in combination with methotrexate (MTX) is approved for the treatment of moderate to severe active RA in adult patients inadequately responsive to DMARDs including MTX. Certolizumab pegol can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. In the U.S., certolizumab pegol is approved for the treatment of adults with moderately to severely active rheumatoid arthritis.

In the U.S., certolizumab pegol is also approved for reducing the signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

Certolizumab pegol is not approved in the indication of psoriatic arthritis. UCB intends to file certolizumab pegol in this indication with global regulatory authorities by the end of 2012.

Source: ucb.com

New efficacy and safety data from the Phase 3 PHOENIX 1 study, one of two pivotal registration trials, showed that maintenance treatment with STELARA® (ustekinumab) for up to five years resulted in consistent, significant clinical response in adults with moderate to severe plaque psoriasis.  Among responders receiving STELARA 45 mg or 90 mg and randomized to continue maintenance therapy through five years, 79 and 81 percent of patients, respectively, experienced at least a 75 percent improvement in psoriasis as measured by the Psoriasis Area and Severity Index (PASI 75) at the end of the treatment period.  Investigators also reported a consistent benefit-to-risk profile for STELARA through five years and observed treatment with the biologic therapy to be generally well-tolerated with rates of adverse events (AEs), including infections, malignancies and cardiovascular events, remaining stable over time.  The data were presented today at the 9th Annual European Academy of Dermatology and Venereology Spring Symposium in Verona, Italy. 

"These data are important to the professional dermatology community as we now have five-year data—the longest continuous study evaluating a biologic in the treatment of psoriasis—that reinforce our understanding of STELARA efficacy and safety as a therapeutic option," said Alexa Kimball, MD, MPH, Associate Professor, Harvard Medical School, Department of Dermatology, Massachusetts General Hospital and lead study investigator.  "STELARA continues to be an important option for dermatologists in the treatment of moderate to severe plaque psoriasis, and these findings are reassuring for physicians and their patients living with this chronic disease who might be candidates for biologic therapy."

In the PHOENIX 1 study, patients were randomized to receive placebo or STELARA 45 mg or 90 mg at weeks 0 and 4.  Following assessment of PASI 75 at week 12, the primary endpoint, STELARA-treated patients continued to receive treatment every 12 weeks.  At week 40, PASI 75 responders were re-randomized to receive maintenance therapy with STELARA or to withdraw from treatment and only receive retreatment with loss of response.  More than two-thirds (n=517) of all STELARA-treated patients (n=753) in PHOENIX 1 continued to receive STELARA through the last scheduled five-year dose.  Among the responders who continued treatment from week 40 through the end of the study, 48 and 59 percent had PASI 90 in the STELARA 45 mg and 90 mg groups, respectively, with up to five years of treatment.  Efficacy was similarly maintained in an overall analysis of the study population, with 63 and 72 percent of all PHOENIX 1 participants achieving PASI 75, and 40 and 49 percent achieving PASI 90, of those individuals receiving STELARA 45 mg or 90 mg, respectively.

Adverse events were evaluated in more than 753 ustekinumab-treated patients with a total 3,104 patient-years (PY) of follow-up.  Rates of AEs (221 and 209 per 100 PY), serious AEs (5.3 and 5.4 per 100 PY) and infections (84 and 82 per 100 PY) in the STELARA 45 mg and 90 mg treatment groups, respectively, remained stable over time.  Rates of serious infection (1.03 per 100 PY), non-melanoma skin cancer (0.45 per 100 PY), malignancy other than non-melanoma skin cancer (0.48 per 100 PY), and major adverse cardiovascular events (0.35 per 100 PY) in combined STELARA groups were similarly consistent over the five-year period.  No new safety signals were reported with the increased duration of exposure. 

Source: prnewswire.com