Chelsea Therapeutics, a pharmaceutical company specializing in treatment for RA and other immunological disease, has been putting efforts to develop an oral anti-inflammatory medication for treating patients suffering from rheumatoid arthritis (RA). The research is presently in Phase I clinical trials in the U.K.

This drug is expected to encourage women to treat their condition in a better way as it is less arduous than the presently recommended treatment options.

The potential therapy that is known as CH-1504 was initially developed by Dr. M. Gopal Nair, a professor and vice-chairman at the department of Biochemistry and Molecular Biology at the University of South Alabama.

From News-Medical.Net:

Current treatment options for RA include over-the-counter oral nonsteroidal anti-inflammatory drugs (NSAIDs) and other pain relievers; oral steroids; but the gold standard for treatment is still methotrexate, a drug that been used for nearly 30 years. Newly available compounds known as biologic response modifiers, such as etanercept and infliximab are used when the disease progresses (mostly in combination with methotrexate) but have to be injected and are very expensive.

While methotrexate is often effective, long-term chronic doses of the drug can be toxic to the liver, kidneys and other organs. Short-term tolerability issues such as nausea, vomiting and diarrhea also often limit its use.

“Given the problems that many patients have tolerating methotrexate along with its long-term safety concerns, a drug candidate that is proven to be as effective or more effective than with fewer side effects would be a major breakthrough in the treatment of RA. This may prompt patients to treat their condition earlier and continue treatment longer,” says Dr. Pedder.

According to Dr. Simon Pedder, CEO of Chelsea Therapeutics, drug candidates such as CH-1504 may help younger women to go for early treatment of RA and get benefited from effective management.

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According to a Saint Louis University study, sleep problems of 80-90 percent children suffering from obstructive sleep apnea (OSA) can be effectively treated with a tonsillectomy and adenoidectomy surgery.

This study was the largest to date and focused on potential factors such as age and ethnicity, which may have an effect on OSA diagnosis and surgery impact.

Ron Mitchell, M.D., professor of pediatric otolaryngology at Saint Louis University and the study’s author, said that OSA has a significant impact on life quality of children, much like chronic asthma or rheumatoid arthritis.

From News-Medical.Net:

“Even though OSA resolved in the overwhelming majority of children after the surgery, it is still crucial to identify and treat children with persistent OSA,” Mitchell says. “Otherwise these children will continue to experience the health, behavioral and learning problems associated with OSA.”

Several options for treating persistent OSA exist, including: nasal steroids, allergy treatment, additional surgery or continuous positive airway pressure (CPAP) mask. Over time, some children who did not experience immediate resolution will normalize, Mitchell says. Children who are overweight must lose weight in conjunction with the surgery for a successful outcome.

Obese children and children with Down’s syndrome or other genetic disorders that affect the craniofacial anatomy were excluded from the study because the rate of OSA is known to be higher.

It was emphasized by Dr. Mitchell that children scoring way outside normal parameters on behavioral measures were the greatest beneficiaries of the surgery.

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According to a presentation made at the annual meeting of the American College of Rheumatology in Philadelphia, a drug that was previously approved for treating non-Hodgkin’s B cell lymphoma and rheumatoid arthritis can prove effective for treating severe ANCA-associated vasculitis on the lines of cyclophosphamide, the current standard therapy.

The drug, Rituxan, works at least as well as cyclophosphamide.

In the study, patients were administered with steroids and randomized to receive either the standard treatment with cyclophosphamide or Rituxan at a dose of 75 mg/m2 weekly for four weeks.

From Sciencedaily.com:

“The reason this is a big deal is that this is a disease where people would come in and be told ‘listen, we are probably going to be able to get on top of your life-threatening disease by using cyclophosphamide, there is the potential for major side effects down the road from this drug,’” said Robert Spiera, M.D., an associate attending rheumatologist at Hospital for Special Surgery in New York. “This study provides strong evidence that Rituxan works as well as cyclophosphamide, at least in terms of getting patients into remission, and over that acute hump of being very ill. And, we can treat patients without the likelihood of causing infertility or causing secondary cancers, which have been a concern with the use of cyclophosphamide.”

Hospital for Special Surgery was one of nine centers involved in the Phase III trial that was led by Ulrich Specks, M.D., a professor of medicine in the Department of Pulmonary and Critical Care Medicine at the Mayo Clinic, and John Stone, M.D., MPH, director, Clinical Rheumatology, Massachusetts General Hospital.

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CH-1504, a potential oral drug for treating rheumatoid arthritis (RA), can encourage women to treat their condition at an early stage as it is less arduous than presently available treatment options. It is important to note that early treatment becomes all important as rheumatoid arthritis generally develops between the ages of 35-50 years and is approximately 2-3 times more prevalent in women.

This potential therapy was initiated by Dr. M. Gopal Nair, a professor and vice-chairman at the department of Biochemistry and Molecular Biology at the University of South Alabama.

From News-Medical.Net:

Current treatment options for RA include over-the-counter oral nonsteroidal anti-inflammatory drugs (NSAIDs) and other pain relievers; oral steroids; but the gold standard for treatment is still methotrexate, a drug that been used for nearly 30 years. Newly available compounds known as biologic response modifiers, such as etanercept and infliximab are used when the disease progresses (mostly in combination with methotrexate) but have to be injected and are very expensive.

While methotrexate is often effective, long-term chronic doses of the drug can be toxic to the liver, kidneys and other organs. Short-term tolerability issues such as nausea, vomiting and diarrhea also often limit its use.

“Given the problems that many patients have tolerating methotrexate along with its long-term safety concerns, a drug candidate that is proven to be as effective or more effective than with fewer side effects would be a major breakthrough in the treatment of RA. This may prompt patients to treat their condition earlier and continue treatment longer,” says Dr. Pedder.

Dr. Simon Pedder, CEO of Chelsea Therapeutics, remarked that drug candidates such as CH-1504 may help younger women to comply with early RA treatment besides considerably improving their outlook when it comes to the management of conditions even into their later years.

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According to results featured in an issue of Arthritis & Rheumatism, low doses of Rituximab can prove effective for achieving remission for rheumatoid arthritis (RA) patients without serious side effects and a need for prescribing harsh steroids.

The involved researchers honed in on a new target, the B cell for attaining this finding.

From News-Medical.Net:

Steroids, whether received intravenously or orally, showed no significant correlation with disease improvement scores among the rituximab groups. Intravenous steroid, however, showed a positive correlation to improved tolerability during the first rituximab infusion in both dosage groups. Overall, adverse events associated with rituximab were mild and easily managed. Headache was the most common complaint.

Confirming the role of B cells in the inflammatory processes behind RA, this study demonstrates the effectiveness and safety of a unique biologic therapy, in moderate doses and independent of steroids. Yet, as its leading author, Dr. Paul Emery, notes, further studies are needed before applying the results to the routine treatment of RA patients. “Both doses of rituximab explored in this study warrant further differential exploration and longer-term followup,” he stresses.

Rituximab, a biologic agent that selectively depletes B cells, was then successfully used for treating non-Hodgkin’s lymphoma apart from facilitating improvements in the disease symptoms for RA patients.

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As per the biggest study of its kind, rituximab that is used to treat rheumatoid arthritis (RA) is safe and effective at the same time. The results of this study were presented for the first time at the Annual European Congress of Rheumatology, EULAR 2005, in Vienna.

It was remarked by lead author, Professor Paul Emery from the University of Leeds in the UK, of the DANCER Study (Double blind placebo controlled dose ranging study) that rituximab is very much effective and better option than a placebo.

From News-Medical.Net:

Professor Paul Emery from the University of Leeds in the UK led the DANCER study (Double blind placebo controlled dose ranging study), designed to confirm the efficacy of rituximab for the treatment of patients with active RA who have failed to improve on one or more disease modifying anti-rheumatic drugs (DMARDs). Rituximab targets a specific type of immune cell and helps to control inflammation and pain.

The DANCER study involved 465 men and women who had had arthritis for about 10 years. It examined the relative efficacy of two different dose levels of rituximab, as well as the role of anti-inflammatory drugs, glucocorticoids (steroids), in the treatment programme.

Professor Emery said that findings of this study clearly suggest that rituximab is safe and well-tolerated for patients with rheumatoid arthritis.

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According to a published study in an edition of the Journal of Biological Chemistry, researchers have been successful in discovering how rheumatoid arthritis (RA) destroys bone. These new findings have been able to guide attempts to design new drugs for reversing RA-related bone loss and have the ability to address more common forms of osteoporosis.

It is believed that rheumatoid arthritis affects two million Americans and results in serious health risks such as pain and deformity in joints, swelling, and thinning of bone.

From News-Medical.Net:

While the new drugs are effective for many patients, others experience infections and even lymphoma in a few cases. The new drugs are based on bioengineered versions of proteins made by human immune cells called antibodies, and are very expensive to make. Thus, the field has been searching for smaller, simpler chemicals that would be effective, but with lower costs and fewer side effects.

“The significance of our study is that it identifies SMURF1 as the signaling partner through which TNF does damage in RA-related bone loss,” said Lianping Xing, Ph.D., assistant professor of Pathology and Laboratory Medicine at the University of Rochester Medical Center. “That has enabled researchers to begin designing small molecule drugs to shut down the action of Smurf 1 and its relatives. Furthermore, since mice engineered to have less Smurf1 expression develop thicker bones, future drugs that shut down Smurf1 may be also useful against more common forms of osteoporosis simply by changing the dose. Of course, this is early-stage work with many obstacles ahead, but it is exciting nonetheless.”

It was revealed during the study that while traditional RA drugs like steroids and NSAIDs are effective for controlling symptoms, a newer class of drugs (e.g. Humira, Remicade and Enbrel) is effective for reversing the RA process by shutting down TNF alpha activity.

Along with Xing, the study was led by Ruolin Guo, Motozo Yamashita, Laura Yanoso, Lan Zhao, Qian Zhang, Quan Zhou, Di Chen, David G. Reynolds, Hani Awad, Edward Schwarz, Ying Zhang and Brendan Boyce within the Department of Pathology and Laboratory Medicineat University of Rochester.

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According to Dr. Deborah Symmons, MD and Dr. Susan Verstappen, MD, chief investigators from the University of Manchester in Manchester, United Kingdom, the earlier a patient receives steroid injections, the better results would be achieved for his or her rheumatoid condition.

A recently published study in Arthritis Today discussed the results of steroid injections given during the onset of rheumatoid arthritis. The study showed that steroid injections given during the first signs of rheumatoid arthritis might help prevent the progression of the disease in one of ten people for at least a year.

Rheumatoid arthritis is an autoimmune disease, which means the body’s own immune system does not recognize the joints and will therefore attack it. The effects could lead to joint deformity and later on, disability. This disease affects more than 1.3 million people in the United States.

The study was conducted by the Steroids in Very Early Arthritis (STIVEA) team. It involved patients with polyarthritis, any type of arthritis involving more than 5 joints. The group was divided into two, the first given steroids shots while the second group was given placebo injections.

Results showed almost half of the patients who received steroids shots did not acquire RA and 20% were free of RA for a year.

From Little Chicago Review:

According to a recent article published in the May/June issue of Arthritis Today, a new study suggests that a three week course of steroid injections given at the first signs of rheumatoid arthritis (RA) may prevent one in ten people from progressing to RA for at least one year.

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In a study conducted by medical team headed by Dr. Eva Baecklund of Uppsala University Hospital in Sweden, anew aspect of treatment was found. Patients with severe rheumatoid arthritis have an increased risk of getting sick with lymphoma. Lymphoma is a type of cancer which originates in lymphocytes of the immune system. They often originate in lymph nodes, often presenting as a node enlargement (tumor).

The study invloved patients with lymphoma associated with rheumatoid-arthritis. They were compared with patients in the control group, those with rheumatoid arthritis but without lymphoma.

Various information were collected, such as the type of lymphoma, type of steroids used, duration of steroid usage and inflammatory load, from both treatment and control groups.

The risk of rheumatoid arthritis- associated lymphomas was significantly reduced in individuals treated with steroids for over two years. Those who received steroid treatment for less than two years for their rheumatoid arthritis yielded no such reduced risk. The most significant protective steroidal effect was observed in the large B-call lymphoma, the type of lymphoma most commonly associated with rheumatoid arthritis.

The researchers concluded that two years or more of oral steroid treatment decreases the risk of rheumatoid arthritis- associated lymphoma, however, these beneficial effects were not observed if the steroids were taken for less than two years. These effects were not affected by length of RA at onset of steroidal treatment.

According to Dr. Eva Baecklund:

“The pros and cons of corticosteroid treatment in rheumatoid arthritis have been a subject of much debate and long term steroid treatment is often limited as a result of concerns about various side effects. What our data show is a new aspect of steroid treatment. Patients with severe rheumatoid arthritis are at increased risk for malignant lymphomas (cancer in the immune system), but long term steroid treatment may decrease this risk.”

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Rheumatoid arthritis (RA) is a chronic disease in which the body’s immune system attacks and destroys healthy joint tissue. The hands and feet are frequently affected, and as the disease progresses it can cause pain, swelling, deformity and disability.

A review revealed that this disease can be treated with low doses of steroids which inhibit joint damage when used during the early phase of RA. The steroids studied in the review are known as glucocorticoids and include the well-known anti-inflammatory prednisone. This medication is often prescribed in the first few months after diagnosis to relieve the discomfort of RA until slower-acting drugs begin protecting the joints.

From Bio-Medicine:

The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The systematic review is based on 15 studies including 1,414 patients. In most of the studies, patients received low dose s of glucocorticoid pills along with so-called disease-modifying drugs for one to two years. Periodic X-rays revealed the extent of joint erosion and other signs of damage.

Because of the known health risks associated with intensive steroid use, concern persists regarding long-term use at any level. The authors cite a 2006 systematic review covering the adverse effects of low-dose glucocorticoids, which concluded that “few of the commonly held beliefs about their incidence, prevalence and impact are supported by clear scientific evidence.”

All studies except one showed reduced progression of joint damage in patients taking glucocorticoids.

The most immediate concern of low dose of steroids in RA is the reduced bone mineral density. However, recent clinical trials have proven that this side effect can now be readily treated.

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