Pfizer Announces FDA Approval of Xeljanz (tofacitinib) and Xeljanz XR for the Treatment of Active Psoriatic Arthritis

In continuation of my update on tofacitinib 

Pfizer Inc.  announced that the United States Food and Drug Administration (FDA) has approved Xeljanz 5 mg twice daily (BID) and Xeljanz XR (tofacitinib) extended release 11 mg once daily (QD) for the treatment of adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs). Xeljanz/Xeljanz XR is the first and only Janus kinase (JAK) inhibitor approved by the FDA for both moderate to severe rheumatoid arthritis (RA) and active PsA.

“Psoriatic arthritis is a complex and progressive disease with an unpredictable course,” said Angela Hwang, Global President, Inflammation and Immunology, Pfizer. “The approval of Xeljanz is an important step forward for patients seeking new treatments and is a testament to Pfizer’s unwavering commitment to advancing patient care.”

The recommended dose of Xeljanz/Xeljanz XR is in combination with nonbiologic DMARDs, and use in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

The FDA approval of Xeljanz for the treatment of adult patients with active PsA was based on data from the Phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, which consisted of two pivotal studies, OPAL Broaden and OPAL Beyond, as well as available data from an ongoing long-term extension trial, OPAL Balance. The findings from OPAL Broaden and OPAL Beyond were published in October 2017 in the New England Journal of Medicine.

Both pivotal studies met their two primary efficacy endpoints, demonstrating statistically significant improvements in American College of Rheumatology 20 (ACR20) response and change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI) score at three months in patients receiving Xeljanz 5 mg BID treatment in combination with a nonbiologic DMARD, compared to those treated with placebo. In OPAL Broaden, 50% of patients taking Xeljanz 5 mg BID achieved an ACR20 response, compared to 33% of patients taking placebo (p≤0.05), at three months. In OPAL Beyond, 50% of patients achieved an ACR20 response with Xeljanz 5 mg BID, compared to 24% of patients taking placebo (p≤0.05), at three months. In both studies, statistically significant improvements in ACR20 response was also seen with Xeljanz 5 mg BID compared to placebo at week 2, a secondary endpoint and the first post-baseline assessment (OPAL Broaden: 22% and 6% [p=0.0003], respectively; OPAL Beyond: 27% and 13% [p=0.0046], respectively).

“As a practicing rheumatologist, I’ve seen the significant physical impact psoriatic arthritis has on people living with the disease, and many patients are looking for additional therapeutic options,” said Philip Mease, M.D., Swedish Medical Center, University of Washington and study investigator. “I’m pleased that Xeljanz is now available for use in the treatment of this chronic condition.”

The safety profile observed in patients with active psoriatic arthritis treated with Xeljanz was consistent with the safety profile observed in rheumatoid arthritis patients. The most common adverse events observed occurring in greater than 3% of patients on Xeljanz 5 mg BID were nasopharyngitis, upper respiratory tract infection, headache and diarrhea.

“Psoriatic arthritis is a serious and debilitating chronic illness that should be diagnosed and treated early,” said Randy Beranek, president and CEO, National Psoriasis Foundation. “As an organization that advocates for people living with psoriatic arthritis, we welcome the availability of new therapies for treating this disease.”

Pfizer Announces FDA Approval of Xeljanz (tofacitinib) and Xeljanz XR for the Treatment of Active Psoriatic Arthritis

Drug improves disease-free, overall survival after hematopoietic stem cell transplants

In continuation of my update on Abatacept (Orencia)

Results from a phase 2 clinical trial, presented by Seattle Children's Research Institute at the 59th American Society of Hematology (ASH) Annual Meeting, show that the drug Abatacept (Orencia) nearly eliminated life-threatening severe acute graft-versus-host disease (GvHD) in patients receiving hematopoietic stem cell transplants.

Abatacept, when added to the standard drug regimen used to prevent GvHD, reduced the occurrence of acute, grade III-IV GvHD from 32 to 3 percent in pediatric and adult patients who underwent mismatched unrelated donor stem cell transplants to treat advanced cancer and other blood disorders. As a result, patients receiving the post-transplant regimen with abatacept experienced improved disease-free and overall survival compared to those who did not.

Acute GvHD is the most deadly complication that can arise after stem cell transplantation. Graft-versus-host disease occurs when the donated T cells, white blood cells in the immune system that fight infection, launch a vigorous attack on a patient's organs, including the skin, liver, kidneys, lung, and the gastrointestinal tract. For patients receiving cells from an unrelated donor, the rate of mild-to-severe forms of acute GvHD can reach as high as 80 percent, with up to half of patients dying from the most severe forms.

"Given the serious threat of graft-versus-host disease, new approaches to make stem cell transplants safer for patients remain a critical unmet need," said Dr. Leslie Kean, the trial's principal investigator and associate director of the Ben Towne Center for Childhood Cancer Research at Seattle Children's. "To see such striking results in patients at extremely high risk for graft-versus-disease is incredibly encouraging."

Kean first became interested in using abatacept to prevent GvHD based on the immunotherapy drug's success in treating patients with rheumatoid arthritis. In rheumatoid arthritis, abatacept inhibits T-cell activation and prevents the chain of events that lead to debilitating joint inflammation.

Similarly, feasibility studies conducted by Kean found that abatacept blocks the activation of certain T cells after transplant. In their models, abatacept reduced the proliferation and activation of effector T cells. Effector T cells incite GvHD when they become overactive as the patient's immune system starts to rebuild itself from the donor stem cells.

"Preventing graft-versus-host disease and relapse after transplant requires a difficult balance of eliminating the bad, overactive effector T cells, without suppressing the good, regulatory T cells," said Kean, who is also an associate professor of pediatrics at the University of Washington School of Medicine and a member of the Fred Hutchinson Cancer Research Center. "As we make improvements to our toolbox of agents capable of achieving this Holy Grail of stem cell transplant, it's essential to include targeted approaches like abatacept."

The multicenter data presented included two patients cohorts who were enrolled across 18 sites. In the cohort of patients who received transplants from mismatched unrelated donors, all 43 patients received four doses of abatacept with a calcineurin inhibitor and methotrexate. To serve as the control, researchers looked at data from a national database of matched patients receiving two commonly used regimens to prevent GvHD - a calcineurin inhibitor and methotrexate (CNI/MTX) or a calcineurin inhibitor and methotrexate plus anti-thymocyte globulin (+ATG).

At 100 days post-transplant, the cumulative incidence of grade III-IV acute GvHD occurred in 3 percent of patients receiving abatacept compared to 32 percent receiving CNI/MTX and 22 percent receiving +ATG. Patients receiving abatacept had intact immune reconstitution, significant improvement in transplantation-related mortality, no major uncontrolled infection and no increase in disease relapse. Significant survival advantages for the abatacept group were demonstrated at one year post-transplant. Overall survival improved to 85 percent (vs. 57 percent in CNI/MTX and 68 percent in +ATG controls); 79 percent of patients experienced disease-free survival (vs. 50 percent in CNI/MTX and 63 percent in +ATG controls).

The second cohort of 140 patients with human leukocyte antigen-matched unrelated donor transplants completed enrollment in November 2017, with data expected from this randomized double-blind arm of the study in the next six months.

"As a transplant physician, it's beyond heartbreaking to witness a patient develop severe acute graft-versus-host disease after having their leukemia cured through bone marrow transplant," said Kean. "To have a therapy at our disposal that safely targets just the T cells causing graft-versus-host disease would represent a major step forward in stem cell transplantation. It not only offers new hope that we can prevent graft-versus-host disease upfront, but that we can also significantly improve outcomes for patients requiring high-risk transplants."

Drug improves disease-free, overall survival after hematopoietic stem cell transplants

Newly discovered drug-like compound may revolutionize treatment of autoimmune diseases

University of Colorado Boulder researchers have discovered a potent, drug-like compound that could someday revolutionize treatment of rheumatoid arthritis and other autoimmune diseases by inhibiting a protein instrumental in prompting the body to start attacking its own tissue.

"We have discovered a key to lock this protein in a resting state," said Hang Hubert Yin, a biochemistry professor in the BioFrontiers Institute and lead author of a paper, published today in Nature Chemical Biology, describing the discovery. "This could be paradigm shifting."

More than 23.5 million Americans suffer from autoimmune diseases like rheumatoid arthritis, scleroderma and lupus, in which an overzealous immune response leads to pain, inflammation, skin disorders and other chronic health problems.

Three of the top five selling drugs in the United States aim to ease their symptoms. But no cure exists, and treatments are expensive and come with side effects.

"Given the prevalence of these diseases, there is a big push for alternatives," Yin said.

For years, scientists have suspected that a protein called Toll-like receptor 8 (TLR8) plays a key role in the innate immune response. When it senses the presence of a virus or bacteria, it goes through a series of steps to transform from its passive to active state, triggering a cascade of inflammatory signals to fight off the foreign invader. But, as Yin explained, "it can be a double-edged sword" leading to disease when that response is excessive.

Because TLR8 has a unique molecular structure and is hidden inside the endosome -- an infinitesimal bubble inside the cell -- rather than on the cell's surface, it has proven an extremely difficult target for drug development.

"This is a long-sought-after target with very little success," Yin said.

But his study shows a drug-like molecule called CU-CPT8m binds to and inhibits TLR8 and exerts "potent anti-inflammatory effects" on the tissue of patients with arthritis, osteoarthritis and Still's disease, a rare autoimmune illness.

For the study, Yin and his co-authors used high-throughput screening to look through more than 14,000 small molecule compounds to determine whether they had the right chemical structure to bind to TLR8. They identified four that shared a similar structure.

Using that structure as a model, they chemically synthesized hundreds of novel compounds in an effort to find one that perfectly bound to and inhibited TLR8.

Previous efforts to target the protein have focused on shutting it down when it is in its active state. But the compound Yin discovered prevents it from activating while still in its passive state.

"Before, people were trying to close the open door to shut it down. We found the key to lock the door from the inside so it never opens," Yin said.

Much more research is necessary, but that could lead to treatments that strike at the root cause of autoimmune diseases, rather than just treating symptoms.

With help from CU's Technology Transfer Office, Yin has already filed a patent application and hopes to move on to animal studies and clinical trials within the next two years.

In the meantime, the new compound can serve as a first-of-its kind tool to understand exactly what TLR8 and the other nine toll-like receptors do in the body.

"Our study provides the first small molecule tool to shut this protein down so we can understand its pathogenesis," Yin said.

Ref : https://www.colorado.edu/today/2017/11/20/arthritis-autoimmune-disease-discovery-could-lead-new-treatments

Newly discovered drug-like compound may revolutionize treatment of autoimmune diseases

Methotrexate drug holiday improves flu vaccine efficacy in rheumatoid arthritis patients

In continuation of my update on methotrexate

People with RA who stop taking methotrexate treatment for just two weeks after they have a seasonal flu shot can improve the vaccine's efficacy without increasing RA disease activity, according to new research findings presented this week at the 2017 ACR/ARHP Annual Meeting in San Diego.

Rheumatoid arthritis (RA) is a chronic disease that causes   pain,  stiffness,  welling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3million Americans have RA, and the disease typically affects women twice as often as men.

Methotrexate, a widely used immunosuppressant, can lower vaccine efficacy in people with RA. So researchers in Seoul, Republic of Korea, set out to investigate whether patients with RA could improve their response to influenza vaccinations by temporarily pausing methotrexate use for two weeks after their flu shot.

"RA patients are more susceptible to infections, including seasonal flu, due to their underlying abnormal immune function and the treatment-associated immune suppression," said Jin Kyun Park, MD, Assistant Professor of Medicine at Seoul National University Hospital, and a lead author of the study. "RA patients taking methotrexate are at even higher risk of infection and infection-related complications, so it's important that they be vaccinated against preventable infectious diseases. However, the immune suppression decreases vaccine response.

To overcome this shortcoming, our group has been working on a novel immunization protocol for RA patients to optimize vaccine response,  including increasing immunogenicity of flu vaccines."

In this prospective, multicenter, randomized, parallel-group trial conducted from October 2016 to January 2017, 316 RA patients who were taking a stable methotrexate dose were randomly assigned to two groups: 156 continued their regular methotrexate and 160 discontinued their dose for two weeks after receiving their flu shot. All participants were vaccinated with a seasonal, quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata and B-Victoria.

Methotrexate drug holiday improves flu vaccine efficacy in rheumatoid arthritis patients

New anti-inflammatory drug reduces death of existing brain cells then repairs damage after stroke

Researchers at The University of Manchester have discovered that a potential new drug reduces the number of brain cells destroyed by stroke and then helps to repair the damage.

A reduction in blood flow to the brain caused by stroke is a major cause of death and disability, and there are few effective treatments.

A team of scientists at The University of Manchester has now found that a potential new stroke drug not only works in rodents by limiting the death of existing brain cells but also by promoting the birth of new neurones (so-called neurogenesis).  

This finding provides further support for the development of this anti-inflammatory drug, interleukin-1 receptor antagonist (IL-1Ra in short), as a new treatment for stroke. The drug is already licensed for use in humans for some conditions, including rheumatoid arthritis. Several early stage clinical trials in stroke with IL-1Ra have already been completed in Manchester, though it is not yet licensed for this condition.

In the research, published in the biomedical journal Brain, Behavior and Immunity, the researchers show that in rodents with a stroke there is not only reduced brain damage early on after the stroke, but several days later increased numbers of new neurones, when treated with the anti-inflammatory drug IL-1Ra.

Previous attempts to find a drug to prevent brain damage after stroke have proved unsuccessful and this new research offers the possibility of a new treatment.

Importantly, the use of IL-1Ra might be better than other failed drugs in stroke as it not only limits the initial damage to brain cells, but also helps the brain repair itself long-term through the generation of new brain cells.

These new cells are thought to help restore function to areas of the brain damaged by the stroke. Earlier work by the same group showed that treatment with IL-1Ra does indeed help rodents regain motor skills that were initially lost after a stroke. Early stage clinical trials in stroke patients also suggest that IL-1Ra could be beneficial.

The current research is led by Professor Stuart Allan, who commented: "The results lend further strong support to the use of IL-1Ra in the treatment of stroke, however further large trials are necessary."

Drugs designed to target nervous system could control inflammation in the gut, study shows

There's a reason it's called a gut feeling. The brain and the gut are connected by intricate neural networks that signal hunger and satiety, love and fear, even safety and danger. These networks employ myriad chemical signals that include dopamine, a powerful neurotransmitter most famous for its role in reward and addiction.

Duke University researchers have shown that manipulating dopamine signaling in the nervous system of the nematode worm C. elegans can control inflammation in the gut.

The study, which appears Aug. 12 in Current Biology, provides a proof of principle that the immune system can be controlled using drugs originally designed to target the nervous system, such as antipsychotics.

"We are talking about an existing set of drugs and drug targets that could open up the spectrum of potential therapeutic applications by targeting pathways that fine-tune the inflammatory response," said Alejandro Aballay, Ph.D., a professor of molecular genetics and microbiology at Duke School of Medicine.

"It is a big leap from worms to humans, but the idea of targeting the nervous system to control the immune system could potentially be used to treat conditions such as rheumatoid arthritis, autoimmune disease, cancer, inflammatory bowel disease, and Crohn's disease," Aballay said.

Recent research suggests that the wiring between the gut and the brain is involved in many other maladies, including autism, anxiety, depression, Alzheimer's disease, and Parkinson's disease.

Aballay believes that C. elegans provides an excellent model for dissecting this complex cross-talk between the nervous system and the immune system. This tiny, transparent worm has a simple nervous system, consisting of only 302 neurons compared to the roughly 100 billion neurons in the human brain. Yet the worm also has a very basic, rudimentary immune system.

Aballay and his team first stumbled upon the gut-brain connection a few years ago when they were studying the immune system of C. elegans. The worms were subjected to a barrage of chemicals in search of immune activators that could protect against bacterial infections. Out of more than a thousand different chemical compounds, they identified 45 that turned on an immune pathway. Curiously, half of those were involved in the nervous system, and a handful blocked the activity of dopamine.

In this study, Aballay decided to examine the effects of dopamine and dopamine signaling pathways on immunity.

Graduate student Xiou Cao blocked dopamine by treating animals with chlorpromazine, a dopamine antagonist drug used to treat schizophrenia and manic depression in humans. He found that these worms were more resistant to infection by the common pathogen Pseudomonas aeruginosa than counterparts that hadn't received the drug.

When Cao then treated the animals with dopamine, it generated the opposite effect, rendering them more susceptible to infection.

The researchers believe their findings indicate that dopamine signaling acts by putting the brakes on the body's inflammatory response so it doesn't go too far.

"Worms have evolved mechanisms to deal with colonizing bacteria," Aballay said. "That is true for us as well. Humans have trillions of microorganisms in our guts, and we have to be careful when activating antimicrobial defenses so that we mainly target potentially harmful microbes, without damaging our good bacteria -- or even our own cells -- in the process."

"The nervous system appears to be the perfect system for integrating all these different physiological cues to keep the amount of damage in check," Aballay said.

Aballay plans continue his studies in C. elegans to identify the different cues involved in fine-tuning the immune response. He also thinks it is worth looking at different analogues or different doses of dopamine antagonists to see if their effects on psychosis can be separated from their effects on immunity.

Drugs designed to target nervous system could control inflammation in the gut, study shows

New research shows how cholesterol medicine has beneficial effect on immune defence system

In continuation of my update on simvastatin,  

The cholesterol medicine simvastatin, which is one of the most commonly used pharmaceuticals in the world, also has a beneficial effect on the immune defence system with regard to diseases such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. Danish researchers have now explored why this is so, and their findings may result in improved treatment.

New research from Aarhus University has demonstrated how simvastatin, one of the most commonly used medicines in the world - typically prescribed to reduce cholesterol - also has a direct effect on the immune defence system. This discovery opens up new opportunities for treating chronic inflammatory diseases.

Sought-after explanation of unexpected effect

The immune defence system, which normally protects the body against infections and foreign bodies, sometimes attacks the body's own tissue. This error in the immune system - whose cause is unknown - results in a chronic state of inflammation which breaks down the tissue. This, in turn, triggers diseases such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes.

In the case of multiple sclerosis, the immune defence system destroys the central nervous system, while the inflammation affects the kidneys, eyes and sense of touch in both type 1 and type 2 diabetes, leading to a variety of complications. However, simvastatin has been shown to reduce the level of inflammation in these diseases, even though it sometimes has to be administered in high concentrations to have any effect. The reason why it does so has eluded researchers thus far.

"Simvastatin - and statins in general - are not designed to have this effect. We have now identified a new mechanism that forms the basis for the effect, and this opens up new opportunities for developing a better substance to combat these inflammatory diseases. It's an interesting line to pursue because a great many people can take statins without significant side effects," relates Thomas Vorup-Jensen, Professor at the Department of Biomedicine at Aarhus University.

The reason for the positive effect is that the pharmaceutical acts as a 'plug' in the proteins that retain the immune cells in the inflammation zones. With the plug in place, the immune cells can no longer contribute to the inflammation, which is therefore reduced, leaving the patient feeling better. In the case of diabetes, for example, it can help reduce the risk of patients developing complications.

"We initially observed this mechanism in the laboratory. Of course, we now need to establish whether it works in the same way in vivo, but we think it's likely," says Thomas Vorup-Jensen.

Anti-inflammatory drugs may improve severity of depressive symptoms, study finds

Anti-inflammatory drugs similar to those used to treat conditions such as rheumatoid arthritis and psoriasis could in future be used to treat some cases of depression, concludes a review led by the University of Cambridge, which further implicates our immune system in mental health disorders.

Researchers from the Department of Psychiatry at Cambridge led a team that analysed data from 20 clinical trials involving the use of anti-cytokine drugs to treat a range of autoimmune inflammatory diseases. By looking at additional beneficial side-effects of the treatments, the researchers were able to show that there was a significant antidepressant effect from the drugs compared to a placebo based on a meta-analysis of seven randomised controlled trials. Meta-analyses of the other types of clinical trials showed similar results.

When we are exposed to an infection, for example influenza or a stomach bug, our immune system fights back to control and remove the infection. During this process, immune cells flood the blood stream with proteins known as cytokines. This process is known as systemic inflammation.

Even when we are healthy, our bodies carry trace levels of these proteins - known as 'inflammatory markers' - which rise exponentially in response to infection. Previous work from the team found that children with high everyday levels of one of these markers are at greater risk of developing depression and psychosis in adulthood, suggesting a role for the immune system, particularly chronic low-grade systemic inflammation, in mental illness.

Inflammation can also occur as a result of the immune system mistaking healthy cells for infected cells and attacking the body, leading to autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis and Crohn's disease. New types of anti-inflammatory drugs called anti-cytokine monoclonal antibodies and cytokine inhibitors have been developed recently, some of which are now routinely used for patients who respond poorly to conventional treatments. Many more are currently undergoing clinical trials to test their efficacy and safety.

The team of researchers carried out a meta-analysis of these clinical trials and found that the drugs led to an improvement in the severity of depressive symptoms independently of improvements in physical illness. In other words, regardless of whether a drug successfully treated rheumatoid arthritis, for example, it would still help improve a patient's depressive symptoms. Their results are published today in the journal Molecular Psychiatry.

Anti-inflammatory drugs may improve severity of depressive symptoms, study finds: Anti-inflammatory drugs similar to those used to treat conditions such as rheumatoid arthritis and psoriasis could in future be used to treat some cases of depression, concludes a review led by the University of Cambridge, which further implicates our immune system in mental health disorders.

Research finding offers hope for more powerful aspirin-like drugs

Researchers have found that salicylic acid targets the activities of HMGB1, an inflammatory protein associated with a wide variety of diseases, offering hope that more powerful aspirin-like drugs may be developed.

Aspirin is one of the oldest and most commonly used medicines, but many of its beneficial health effects have been hard for scientists and physicians to explain. A recent study conducted by researchers at the Boyce Thompson Institute (BTI), in collaboration with colleagues at Rutgers University and San Raffaele University and Research Institute, shows that aspirin's main breakdown product, salicylic acid, blocks HMGB1, which may explain many of the drug's therapeutic properties. The findings appear Sept. 23, 2015 in the journal Molecular Medicine.

"We've identified what we believe is a key target of aspirin's active form in the body, salicylic acid, which is responsible for some of the many therapeutic effects that aspirin has. This protein, HMGB1, is associated with many prevalent, devastating diseases in humans, including rheumatoid arthritis, heart disease, sepsis and inflammation-associated cancers, such as colorectal cancer and mesothelioma," said senior author Daniel Klessig, a professor at BTI and Cornell University.

Aspirin's pain relieving effects have long been attributed to its ability to block the enzymes cyclooxygenase 1 and 2, which produce prostaglandins--hormone-like compounds that cause inflammation and pain--a discovery that netted its discoverer, John Vane, a Nobel prize. However, the body rapidly converts aspirin to salicylic acid, which is a much less effective inhibitor of cyclooxygenase 1 and 2 than aspirin. Nonetheless, it has similar pharmacological effects as aspirin, suggesting that salicylic acid may interact with additional proteins.

"Some scientists have suggested that salicylic acid should be called 'vitamin S', due to its tremendous beneficial effects on human health, and I concur," said lead author Hyong Woo Choi, a research associate at BTI.

In the current study, researchers discovered the interaction between salicylic acid and HMGB1 by screening extracts prepared from human tissue culture cells to find proteins that could bind to salicylic acid. They identified one of these proteins as HMGB1. These screens have also identified a key suspect in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, plus approximately two dozen additional candidates that have yet to be characterized.

To further investigate the interactions between salicylic acid and HMGB1's role in the body, Klessig worked with Marco Bianchi of San Raffaele University and Research Institute, who initially discovered that HMGB1 is a trigger of inflammation. Using assays that measured the effects of salicylic acid on the recruitment and activation of immune cells, they showed that salicylic acid could block both of these functions at concentrations similar to those found in people on low-dose aspirin.

"We've found that HMGB1 is involved in countless situations where the body confronts damage to its own cells, which occur in many disease conditions. In retrospect, it's almost obvious that a very general anti-inflammatory compound blocks a very general inflammation trigger," said Bianchi.

Klessig also teamed up with biophysicist Gaetano Montelione at Rutgers, The State University of New Jersey, to not only confirm that salicylic acid can bind to HMGB1, but also to identify the salicylic acid binding sites.

More at research paper

Research finding offers hope for more powerful aspirin-like drugs

AbbVie reports positive results from ABT-494 Phase 2 clinical trials in patients with rheumatoid arthritis

AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced results from two Phase 2 clinical trials evaluating its investigational selective JAK1 inhibitor, ABT-494, in patients with inadequate response to either methotrexate or TNF inhibitors. The clinical trials, BALANCE-I and BALANCE-II, achieved ACR20 at week 12 across all dose levels, except the lowest dose in BALANCE-II. BALANCE-I and BALANCE-II evaluated patients with moderate to severe rheumatoid arthritis with inadequate responses to prior anti-TNF (TNF-IR) or methotrexate (MTX-IR) treatment, respectively.

"We believe ABT-494 has the potential to become a best-in-class therapy, particularly in the most challenging patient population of TNF-inadequate responders," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are encouraged by the results of our Phase 2 studies and we will advance ABT-494 to Phase 3 studies with a once-daily formulation."

AbbVie reports positive results from ABT-494 Phase 2 clinical trials in patients with rheumatoid arthritis

Chemical compound shows promise in treating rheumatoid arthritis

Montana State University researchers and their collaborators have published their findings about a chemical compound that shows potential for treating rheumatoid arthritis.

The paper ran in the June issue of the Journal of Pharmacology and Experimental Therapeutics (JPET), and one of its illustrations is featured on the cover. JPET
is a leading scientific journal that covers all aspects of pharmacology, a field that investigates the effects of drugs on biological systems and vice versa.

"This journal is one of the top journals that reports new types of therapeutics that are being developed," said Mark Quinn, senior author on the paper and a professor in MSU's Department of Microbiology and Immunology. The department is part of the College of Agriculture and the
College of Letters and Science.

Rheumatoid arthritis is a chronic autoimmune disorder that affects an estimated 1.3 million people in the world, Quinn said. Characterized by stiff, swollen joints, it's a progressive disease that occurs when the body's immune system attacks its own cells. Inflammation in the lining of the joints leads to loss of bone and cartilage. People who have rheumatoid arthritis lose mobility and joint function without adequate treatment.

New kinds of drugs have been developed for treating the disease, Quinn said. Called biological drugs, or "biologics," they are made from genetically engineered proteins or antibodies that act on substances in the immune system. When used to treat rheumatoid arthritis, they interrupt signals that fuel the inflammatory process. Two such drugs are ENBREL and HUMIRA.

Biologics can be expensive, however, and some people don't respond to
them, Quinn said. Some people respond at first, but not forever.

"There is a real need to develop new kinds of drugs that are different," Quinn said. "They could be combined with other available drugs or replace drugs that aren't working for patients."

Researchers in his laboratory and elsewhere identified a new chemical compound, called IQ-1S, in a previous study, Quinn said. Then they conducted a new study to understand how the   small-molecule  compound
works against rheumatoid arthritis. They explained their findings in the JPET paper.  

Ref : http://jpet.aspetjournals.org/content/353/3/505.abstract?sid=8b8e3977-7bbd-40f4-ab43-f37402878df0

Chemical compound shows promise in treating rheumatoid arthritis: 

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Effimune announced today that it had received the authorization from the Belgian regulatory authority, the FAMHP (Federal Agency for Medicines and Health Products) for a Phase I clinical trial of FR104, its drug candidate for controlling the regulation of the immune system.

This double-blind randomized clinical trial will take place on 70 healthy volunteers (both men and women) over a period of 9 months, and will prepare the future development of FR104 in rheumatoid arthritis and kidney transplantation. The primary objectives of the trial are to establish the safety and tolerability of FR104 and assess its pharmacodynamics and pharmacokinetics. Since September 2013, FR104 has been under a global license agreement with Janssen Biotech, Inc., a subsidiary of Johnson & Johnson.

Benzoic acid, 2,3,4,5-tetrachloro-6-(2, 4,5,7-tetrabromo-6-hydroxy-3-oxo-3H-xanthen-9-yl) -

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Can-Fite BioPharma Ltd.  a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that it completed the design of the Rheumatoid Arthritis (RA) Phase III study of its lead drug candidate CF101. Dr. M. Silverman, Can-Fite Medical Director, and Dr. Lee Simon, a key opinion leader in the field of autoimmune inflammatory diseases, designed the Phase III clinical study.

The Phase III study will be a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that will investigate the efficacy and safety of daily CF101 administered orally as a monotherapy for 12 weeks to patients with active RA. The study will have three arms, a 2 mg CF101 dose, a 3mg CF101 dose and placebo, given orally twice daily in the form of tablets. Approximately 300 patients are expected to be enrolled in the study, where sample size for each treatment group will be approximately 100 patients and will provide a statistical power of at least 90%. The study primary end point will be ACR 20 response at Week 12. The A3 adenosine receptor biomarker will be evaluated prior to treatment and its correlation to patients' response to the drug will be analyzed upon study conclusion.

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Mylan announces U.S. launch of Celecoxib Capsules

In continuation of my update celecoxib

Mylan Inc. (Nasdaq: MYL)      announced the U.S. launch of its Celecoxib Capsules,   50 mg,  100 mg,  200 mg, and 400 mg,  one  of the  first  available  generic  versions        of   Pfizer's elebrex®       Capsules,     which    is   indicated for  the  relief  of the  signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, and for the management of acute pain in adults.

Celecoxib Capsules, 50 mg, 100 mg, 200 mg, and 400 mg, had U.S. sales of approximately $2.5 billion for the 12 months ending September 30, 2014, according to IMS Health.

Currently, Mylan has 286 ANDAs pending FDA approval representing $111.6 billion in annual brand sales, according to IMS Health. Forty-five of these pending ANDAs are potential first-to-file opportunities, representing $29.5 billion in annual brand sales, for the 12 months ending June 30, 2014, according to IMS Health.

Mylan announces U.S. launch of Celecoxib Capsules

Destroy Cancer Naturally in 40 Days

We know that, Tripterygium wilfordii, or léi gōng téng (Mandarin) (Chinese:雷公藤, Japanese: raikōtō), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine for treatment of fever, chills, edema and carbuncle.

Tripterygium wilfordii recently has been investigated as a treatment for a variety of disorders including rheumatoid arthritis,cancer, chronic hepatitis, chronic nephritis, ankylosing pondylitis, polycystic kidney disease as well as several skin disorders. It is also under investigation for its apparent antifertility effects, which it is speculated, may provide a basis for a Male oral contraceptive. Now University of Minnesota Masonic Cancer Center, researchers have reported that, ancient Chinese medicine is bringing renewed hope to cancer sufferers, all thanks to an herb called thunder god vine. For starters, this herb may make it possible to purge tumors from the body without resorting to chemotherapy or other intense interventions.

On top of that, early evidence shows thunder god vine could be particularly effective in hindering the growth of pancreatic, colorectal, and ovarian cancers, among others.

Destroy Cancer Naturally in 40 Days | Cancer Defeated

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

A new drug combination for rheumatoid arthritis treats the disease just as well as other intensive treatment strategies but with less medication and fewer side effects at a significantly lower cost. Doctoral researcher Diederik De Cock (KU Leuven) describes the strategy in a new study published in Annals of Rheumatic Diseases.

Rheumatoid arthritis (RA) is a chronic auto-immune disease that causes pain and stiffness in the joints, fatigue, bone damage and, eventually, loss of mobility. RA afflicts around 1% of people in the western world; in Belgium, 80,000 to 100,000 people currently live with the disease.

Because there is no known cure for RA, physicians focus treatment on suppressing disease activity. Therapies have improved in recent years, and clinical studies show that intensive treatment of early RA can prevent joint damage and improve patients' quality of life.

In the two-year study, called 'CareRA' (Care in early RA), researchers and clinicians in the rheumatology unit at University Hospitals Leuven examined various therapies for early RA. Their goal: to find the optimal combination and dosage of three commonly prescribed antirheumatic drugs (methotrexate, sulfasalazine and leflunomide) in combination with glucocorticoids (a class of steroid hormones).

The researchers divided 290 early RA patients into three treatment groups. Each group received a different combination therapy: 'COBRA Classic' (methotrexate, sulfasalazine and a high first dose of glucocorticoids), 'COBRA Slim' (methotrexate and a moderate dose of glucocorticoids) or 'COBRA Avant-Garde' (methotrexate, leflunomide and a moderate dose of glucocorticoids).

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

Repurposed drug may be first targeted treatment for serious kidney disease

A drug approved for the treatment of rheumatoid arthritis may also turn out to be the first targeted therapy for one of the most common forms of kidney disease, a condition that almost inevitably leads to kidney failure. A team led by Massachusetts General Hospital (MGH) researchers is reporting that treatment with abatacept (Orencia) appeared to halt the course of focal segmental glomerulosclerosis (FSGS) in five patients, preventing four from losing transplanted kidneys and achieving disease remission in the fifth. The report is being issued online in the New England Journal of Medicine to coincide with a presentation at the American Society for Nephrology annual meeting.

Repurposed drug may be first targeted treatment for serious kidney disease

Pfizer reports positive results from two tofacitinib Phase 3 trials for chronic plaque psoriasis

In continuation of my update on Tofacitinib

We know that, Tofacitinib (trade name Xeljanz, formerly tasocitinib, CP-690550) is a drug of the janus kinase (JAK) inhibitor class, discoveredand developed by Pfizer. It is currently approved for the treatment of rheumatoid arthritis (RA) in the United States and is being studied for treatment of psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection. Tofacitinib was not approved by the European regulatory agencies because of concerns over efficacy and safety...

Pfizer reports positive results from two tofacitinib Phase 3 trials for chronic plaque psoriasis

Cell death protein could offer new anti-inflammatory drug target

Scientists in Melbourne, Australia, have revealed the structure of a protein that is essential for triggering a form of programmed cell death called necroptosis, making possible the development of new drugs to treat chronic inflammatory diseases such as Crohn's disease and rheumatoid arthritis.

Ref : http://dx.doi.org/10.1016/j.immuni.2013.06.018

Cell death protein could offer new anti-inflammatory drug target

Unexpected use of former cancer drug, Zebularine...

Researchers at Lund University have unexpectedly discovered that an old cancer drug can be used to prevent rejection of transplanted tissue. The researchers now have high hopes that their discovery could lead to new treatments for both transplant patients and patients with autoimmune diseases.

"Our group were studying the effects of the old tumour drug Zebularine, (see structure) developed in the USA in the 1960s, and by chance we discovered that it had completely unexpected effects on the immune system," says Leif Salford, Senior Professor of Neurosurgery.

"It turned out that Zebularine has the ability to subdue the reaction of the body's immune system. This could be important in situations where tissue or organs are transplanted. We also think it could be used to curb the body's attacks on its own tissue in autoimmune diseases, for instance type 1 diabetes or rheumatoid arthritis," says Dr Nittby.

In studies on animals, the researchers used rats that were made diabetic. The researchers transplanted the islets of Langerhans  cell groups in the pancreas producing insulin -- from healthy rats from another kind of rat into those with diabetes. The diabetic rats were divided into two groups; one group were treated with Zebularine and the other, the control group, did not receive any treatment. The diabetic rats that were treated with Zebularine survived for a significantly longer period than the untreated rats.

"It is very interesting that we only treated them with Zebularine for two weeks, but the effects of the treatment could be observed throughout the 90-day follow-up period.

"The findings are very exciting and are a sign that the immune system was not just generally suppressed, but that the treatment was more targeted. Neither did we see any signs of side-effects," said Dr Nittby.

The researchers are now working intensively to further refine the treatment. The next step is to teach certain cells in the immune system -- the dendritic cells -- to accept certain specific proteins using the Zebularine treatment. This would mean that the treatment could be targeted even more.

Unexpected use of former cancer drug