FDA approves Rituxan to treat two rare disorders

The U.S. Food and Drug Administration today approved Rituxan (rituximab), in combination with glucocorticoids (steroids), to treat patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA), two rare disorders that cause blood vessel inflammation (vasculitis).

Vasculitis in patients with WG and MPA can lead to tissue damage. WG mostly affects the respiratory tract (sinuses, nose, trachea, and lungs) and kidneys, while MPA commonly affects the kidneys, lungs, nerves, skin, and joints. Both of these diseases affect people of all ages and ethnicities, and both genders. The causes of these disorders are unknown, and both are considered orphan diseases because they each affect less than 200,000 people in the United States.

“This new indication for Rituxan provides the first approved therapy for these two orphan diseases,” said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research.

Rituxan is an antibody that is manufactured through biotechnology methods. The drug works by greatly reducing the number of specific immune cells in the blood, known as B cells.

The safety and effectiveness of Rituxan was demonstrated in a single controlled trial, in which 197 patients with WG or MPA were assigned at random to receive either Rituxan plus glucocorticoids once a week for four weeks or oral cyclophosphamide plus glucocorticoids daily to induce remission. After six months, 64 percent of patients treated with Rituxan had complete remission compared to 53 percent of patients treated with cyclosphosphamide.

Retreatment with Rituxan was not formally evaluated; therefore, the safety and efficacy of retreatment with subsequent courses of Rituxan has not been established. More data are needed to determine the safety of more than one course of Rituxan and long term safety of use of Rituxan in patients with WG and MPA. These questions will be further evaluated in a required post-marketing study.

Rituxan carries a Boxed Warning for infusion reactions, which can occur during infusion or within 24 hours afterwards. Other Boxed Warnings for Rituxan include rashes and sores in the skin and mouth (severe mucocutaneous reactions); and progressive multifocal leukoencephalopathy, a brain infection that generally is fatal. Rituxan is not recommended for use in patients with severe, active infections.

The most common side effects in study participants with WG and MPA included infection, nausea, diarrhea, headache, muscle spasms, and anemia.

Rituxan, which has been marketed since 1997, is also indicated for the treatment of patients with non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.

Rituxan is manufactured by San Francisco-based Genentech, a member of the Roche Group.

-----

Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

Study Redefines Placebo Effect as Part of Effective Treatment

/PRNewswire/ -- Researchers used the placebo effect to successfully treat psoriasis patients with one quarter to one half of their usual dose of a widely used steroid medication, according to an early study published online today in the journal Psychosomatic Medicine. Early results in human patients suggest that the new technique could improve treatment for several chronic diseases that involve mental state or the immune system, including asthma, multiple sclerosis and chronic pain.

By designing treatment regimens that mix active drug and placebo, researchers at the University of Rochester Medical Center hope to maximize drug benefits, reduce side effects, increase the number of patients who take their medicine and extend the use of drugs otherwise limited by addiction risk or toxicity. Using a fraction of the usual drug dose to get the same effect could also make possible a dramatic and timely reduction in healthcare costs, according to the authors.

The publication is a product of decades of research in the emerging field of "psychoneuro-immunology," which holds that the ability of the human immune system to fight disease is closely linked with a person's mind. Thoughts and moods are captured in neurochemicals that cause the release of hormones which interact with disease-fighting cells.

The current research team chose psoriasis for their first human experiments because it is chronic, gets worse when patients feel stress and involves the immune system. The condition causes pain and disability in four million Americans as inherited traits and irritants cause the immune system to trigger the too fast production of skin cells, resulting in red, scaly patches of dead skin.

"Our study provides evidence that the placebo effect can make possible the treatment of psoriasis with an amount of drug that should be too small to work," said Robert Ader, Ph.D., M.D. (hc), distinguished university professor in the University of Rochester School of Medicine & Dentistry. "While these results are preliminary, we believe the medical establishment needs to recognize the mind's reaction to medication as a powerful part of many drug effects, and start taking advantage of it," said Ader, professor of Psychiatry and principal investigator of the study. The placebo effect, obviously, cannot help unconscious patients, or replace substances that the body itself is unable to produce, he added. In the absence of functioning islet cells, for example, placebos cannot stimulate the release of insulin in a Type l diabetic.

Study Details

A description of the current findings requires expanding the definition of placebo effects to include phenomena that are not fully understood by modern medicine, Ader said. Although placebos, "dummy pills" that have no therapeutic effect by themselves, are prescribed by many physicians today, their use still carries a stigma. It's as if the effect of a pill containing no medication is not "real," part magic and part deception.

To accurately define and study the placebo effect, Ader and colleagues chose to frame it as an example of a well-established psychological phenomenon: the conditioned response. Nineteenth century Russian physiologist Ivan Pavlov was the first to study the phenomenon of conditioning. By ringing a bell (a conditioned stimulus) each day before giving his dogs food (an unconditioned stimulus), Pavlov found that the dogs would eventually salivate (a conditioned response) at the sound of the bell alone.

In the current study, Ader and colleagues sought to determine if a drug's therapeutic effect could be triggered by qualities associated with the drug, like its shape, color, smell and packaging, as well as by its administration by an authority figure in a white lab coat. These repeated associations, Ader argues, create conditioned responses, drug-like therapeutic effects of treatment caused, not by a drug's ingredients alone, but elicited by stimuli associated with the effects of active drug treatment. The results provide the first evidence that conditioned responses might be harnessed to influence the design of drug regimens in humans.

Research teams at the University of Rochester Medical Center and Stanford University conducted an 11 to 14-week, double-blind, randomized clinical trial in 46 patients with mild-to-moderate psoriasis. Patients were on no other medications during the study, and had signed consent forms after being informed they might receive a reduced dose of topical steroid.

At the start of the study, researchers randomly selected two "target" psoriatic lesions or sores on each patient. Twice each day during a three-week baseline period, all patients spread a lotion containing a full dose of steroid medication (0.1% Aristocort A, triamcinolone acetonide) onto one of their two study lesions. The second lesion was coated with a moisturizing cream. Medicated and unmedicated creams were distributed in coded syringes to make them indistinguishable.

Nearly all past drug studies divided patients into two groups only. One would get the full dose of the drug all of the time (a 100 percent reinforcement schedule). The other would get zero drug all of the time (zero percent reinforcement). The current study asks for the first time: what if we treat patients with something in between drug and placebo? After the three-week baseline period, patients were randomly assigned to one of three groups.

The first continued to receive 100 percent of the treatment drug at each administration for the rest of the study on his or her study lesion. A second, the partial reinforcement group, also continued to receive a full dose, but only 25 or 50 percent of the time, and a steroid-free emollient the rest of the time. The study was designed so that this second group could benefit from exposure to cues they had previously associated with active drug treatment (a conditioned therapeutic effect). A third group, the "dose control group," received active drug at every administration, but at 25 or 50 percent of the full dose used in the first and second groups. Thus, the partial reinforcement and "dose control" groups received the same total amount of active medication, but in different patterns.

Results were measured in two ways. First, a "blinded" dermatologist measured the severity of a patient's psoriasis lesions weekly using the Psoriasis Severity Scale (PSS), a standard tool used to track the redness, hardening and thickening of skin. The second measure was whether a patient experienced a "relapse" in lesion severity, defined arbitrarily as a return to a PSS score within two units of a patient's initial score.

In terms of the overall PSS severity scores, results were mixed. The Stanford study site found no group differences in PSS scores that could be attributed to the different treatment regimens. Ader believes that elevated baseline PSS scores in the randomly selected Dose Control subjects at Stanford might have obscured the differences between the dose control and partial reinforcement groups. For instance, results could have been influenced by differences in the amount of sun patients were exposed to in Upstate New York and California (ultraviolet light is an established treatment for psoriasis).

In Rochester, there were no differences between the PSS values of the Partial Reinforcement and Dose Control groups at the point in the study where experimental treatment began. In this case, partial reinforcement brought about a greater reduction in lesion severity during the experimental period than continuous reinforcement (dose control) with the same cumulative amount of drug.

The relapse results were clearer. Four of 18 patients (22.2 percent) in the 100 percent reinforcement group (full dose all the time) relapsed within the eight-week experimental period. Among patients treated with a full dose of drug, but one half or one quarter of the time (50 or 25 percent reinforcement schedule), four of 15 patients (26.7 percent) relapsed. Thus, the incidence of relapse did not differ substantially between patients receiving a full dose of drug all the time and those treated under the partial reinforcement schedules, researchers said. In contrast, eight of the 13 patients (61.5 percent) in the dose control group who received active drug each time, but not the full does, relapsed in the same period of time.

Thus, the incidence of relapse in the partial reinforcement group (26.7 percent) was significantly less than in dose control patients (61.5 percent) that received the same cumulative amount of drug. Further studies are underway, and others are planned, to confirm the effect, answer the questions raised and explore the effect in other autoimmune diseases.

The study was conducted jointly by the Departments of Psychiatry and Dermatology within the School of Medicine & Dentistry at the University of Rochester and the Stanford University School of Medicine. Along with Ader, the study was authored in Rochester by Mary Gail Mercurio, James Walton and Deborra James. Leading the effort at Stanford were David Fiorentino, Alexa Kimball, Michael Davis and Valerie Ojha. The study was funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health (NIH).

"The pharmaceutical industry may choose to ignore the conditioning component of drug treatment regimens," Ader said. "Alternatively, they may now consider exploring ways to exploit conditioning in the design of drug treatment protocols, especially in chronic conditions where patients acquire conditioned responses over time. I believe industry will eventually support this approach because it promises to increase safety and reduce production costs."

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page

FDA Warns Consumers Not to Use Body Building Products Marketed as Containing Steroids or Steroid-Like Substances

The U.S. Food and Drug Administration today issued a Public Health Advisory (PHA) warning consumers to stop using body building products that are represented as containing steroids or steroid-like substances. Many of these products are marketed as dietary supplements.

The agency also issued a Warning Letter to American Cellular Laboratories Inc. for marketing and distributing body building products containing synthetic steroid substances. Although these products are marketed as dietary supplements, they are not dietary supplements, but instead are unapproved and misbranded drugs.

The PHA notifies consumers and health care professionals that the FDA has received reports of serious adverse events associated with the use of body building products that claim to contain steroids or steroid-like substances. Those adverse events include cases of serious liver injury, stroke, kidney failure and pulmonary embolism (artery blockage in the lung). The PHA also advises consumers to stop taking body building products from any manufacturer that claim to contain steroid-like substances or to enhance or diminish androgen-, estrogen-, or progestin-like effects in the body.

The FDA has received five adverse event reports, including serious liver injury, in men taking products marketed as dietary supplements by American Cellular Laboratories including TREN-Xtreme and MASS Xtreme. Acute liver injury is generally known to be a possible side effect of using products that contain anabolic steroids. Some of the cases resulted in hospitalization, but there were no reports of death or acute liver failure.

“Products marketed for body building and claiming to contain steroids or steroid-like substances are illegal and potentially quite dangerous,” said Commissioner of Food and Drugs Margaret A. Hamburg, M.D. “The FDA is taking enforcement action today to protect the public.”

The products listed in the Warning Letter to American Cellular Laboratories Inc., include “TREN-Xtreme,” “MASS Xtreme,” “ESTRO Xtreme,” “AH-89-Xtreme,” “HMG Xtreme,” “MMA-3 Xtreme,” “VNS-9 Xtreme,” and “TT-40-Xtreme,” and are sold on the Internet and in some stores. These products, which claim to contain steroid-like ingredients but in fact contain synthetic steroid substances, are unapproved new drugs because they are not generally recognized as safe and effective. In addition, the products are misbranded because the label is misleading and does not provide adequate directions for use.

Consumers taking body building supplements that claim to contain steroids or steroid-like substances should stop taking them immediately. Consumers should also consult a health care professional if they suspect they are experiencing problems associated with the products. Health care professionals and consumers are encouraged to report adverse events that may be related to the use of these types of products to the FDA's MedWatch Program by phone at 1-800-FDA-1088 or by fax at 1-800-FDA-0178 or by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787.

-----
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page
www.artsacrossgeorgia.com
Arts Across Georgia