July 6 -- Simpler and shorter treatment with antibiotic drugs could help prevent full-blown tuberculosis in millions of people worldwide infected with the bacterium that causes TB, especially those also infected with HIV, researchers report.
TB, or tuberculosis, is the leading cause of death among people co-infected with HIV, the virus that causes AIDS. About half a million people with both infections die worldwide every year.
The new study by an international team of scientists included 1,148 South African men and women infected with the TB bacterium and HIV, who were followed for up to six years to see whose TB infections stayed dormant.
It found that the most streamlined combination treatment -- a high dose of 900 milligrams each of the newer antibiotic rifapentine (Priftin) and the traditional anti-TB antibiotic isoniazid once weekly for three months -- worked as well or better than the current gold standard of care of 300 mg of isoniazid taken daily for six months or longer.
Of the study volunteers, about 3.1 percent on the shorter drug regimen developed active TB or died each year, compared to 3.6 among those on the standard daily regimen. Without treatment, researchers estimated that the mortality rate would have doubled.
Compliance with the drug regimen was also 95 percent for the shorter regimen, compared to 60 percent that other studies showed for the standard regimen.
The study appears online July 7 in the New England Journal of Medicine.
"This new, simpler treatment regimen with rifapentine and isoniazid is highly effective and could transform therapy for latent tuberculosis in both those co-infected with HIV and those not," senior author Dr. Richard Chaisson, a professor of infectious diseases at the Johns Hopkins University School of Medicine and founding director of its Center for Tuberculosis Research, said in a Hopkins news release.
"New treatment options are urgently needed to help control TB globally, and simpler regimens will substantially increase the number of people receiving therapy," Chaisson added.
He noted that fewer than 1 percent of those infected and most likely to develop full-blown TB receive drug treatment because of factors such as inconvenience, drug side effects and difficulty finding nearby health clinics.
http://www.drugs.com/news/new-combo-therapy-may-prevent-tb-save-lives-hiv-32368.html
Showing posts with label Rifapentine. Show all posts
Showing posts with label Rifapentine. Show all posts
Monday, 18 July 2011
Monday, 23 May 2011
TUBERCULOSIS: TB Drugs Show Surprising Equality
Michael Smith : May 19, 2011
DENVER -- Two rifamycin derivatives had equal efficacy against pulmonary tuberculosis in an international, phase II trial, a researcher said here.
Rifapentine (Priftin) and rifampin (Rifadin, Rimactane) showed equal activity when they were added to standard therapy during the first eight weeks of treatment, according to Susan Dorman, MD, of Johns Hopkins University.
But the result was surprising because animal studies had suggested that rifapentine would be markedly better, Dorman said in a late-breaking abstract session at the annual meeting of the American Thoracic Society.
The rifamycin derivatives are "key sterilizing components of current standard treatment for active TB," Dorman said. Of those drugs, rifampin is the most widely used, but it may not be the best, she added.
In particular, less rifapentine is needed to inhibit a given amount of Mycobacterium tuberculosis, and it lasts longer in the body than rifampin, she said.
Studies in mice showed that treatment with rifapentine cured TB in three months compared with six months for rifampin, Dorman added. "There is a need for shorter regimens" in humans, she noted.
To test the compound in humans, she and colleagues added either it or rifampin to standard early therapy -- isoniazid (Nydrazid, Tubizid), pyrazinamide, and ethambutol (Myambutol) -- five days a week for eight weeks.
The goal was see if there were differences in the proportion of patients with negative sputum cultures at the end of the intensive phase of treatment, Dorman said.
The researchers also evaluated safety and tolerability, she said.
All told, 531 patients took part, almost half of them in Africa; 255 were assigned to the rifampin arm and 276 to rifapentine. About 70 participants in each arm were either lost to follow up or were found not to be eligible, Dorman reported.
The researchers had expected to see a 15% difference in the rate of culture negativity, Dorman said, but instead the difference was about 3%.
Specifically:
When the sputum samples were analyzed in liquid media, 71.5% of rifampin patients and 75.3% of rifapentine patients had negative cultures after eight weeks.
In solid media, the proportions were 88.9% and 91.9%, respectively.
Neither difference was statistically significant.
Both drugs appeared equally safe and tolerable, Dorman reported.
In the rifampin arm, 15.7% of patients stopped therapy, compared with 14.5% of the rifapentine patients, she said. The rates of adverse events were also similar -- 18.1% for rifampin versus 22.6% for rifapentine -- and 2.8% of rifampin patients reported hepatitis compared with 3.6% of rifapentine patients.
It remains unclear why the expected difference did not materialize, Dorman said, adding that it could be a function of dosing levels or perhaps the fact that both drugs were taken without food.
She noted that the proportion of culture conversions is a surrogate marker for the sterilizing activity of the drugs which may not have been a good reflection of that activity.
The study was supported by the CDC. Study drugs were donated by sanofi-aventis. Dorman said she had no conflicts.
Source reference: Dorman S, et al "A phase II study of a rifapentine-containing regimen for intensive phase treatment of pulmonary tuberculosis: Preliminary results for tuberculosis trials consortium study 29" Am J Respir Crit Care Med 2011; 183: A6413.
http://www.medpagetoday.com/MeetingCoverage/ATS/26575
DENVER -- Two rifamycin derivatives had equal efficacy against pulmonary tuberculosis in an international, phase II trial, a researcher said here.
Rifapentine (Priftin) and rifampin (Rifadin, Rimactane) showed equal activity when they were added to standard therapy during the first eight weeks of treatment, according to Susan Dorman, MD, of Johns Hopkins University.
But the result was surprising because animal studies had suggested that rifapentine would be markedly better, Dorman said in a late-breaking abstract session at the annual meeting of the American Thoracic Society.
The rifamycin derivatives are "key sterilizing components of current standard treatment for active TB," Dorman said. Of those drugs, rifampin is the most widely used, but it may not be the best, she added.
In particular, less rifapentine is needed to inhibit a given amount of Mycobacterium tuberculosis, and it lasts longer in the body than rifampin, she said.
Studies in mice showed that treatment with rifapentine cured TB in three months compared with six months for rifampin, Dorman added. "There is a need for shorter regimens" in humans, she noted.
To test the compound in humans, she and colleagues added either it or rifampin to standard early therapy -- isoniazid (Nydrazid, Tubizid), pyrazinamide, and ethambutol (Myambutol) -- five days a week for eight weeks.
The goal was see if there were differences in the proportion of patients with negative sputum cultures at the end of the intensive phase of treatment, Dorman said.
The researchers also evaluated safety and tolerability, she said.
All told, 531 patients took part, almost half of them in Africa; 255 were assigned to the rifampin arm and 276 to rifapentine. About 70 participants in each arm were either lost to follow up or were found not to be eligible, Dorman reported.
The researchers had expected to see a 15% difference in the rate of culture negativity, Dorman said, but instead the difference was about 3%.
Specifically:
When the sputum samples were analyzed in liquid media, 71.5% of rifampin patients and 75.3% of rifapentine patients had negative cultures after eight weeks.
In solid media, the proportions were 88.9% and 91.9%, respectively.
Neither difference was statistically significant.
Both drugs appeared equally safe and tolerable, Dorman reported.
In the rifampin arm, 15.7% of patients stopped therapy, compared with 14.5% of the rifapentine patients, she said. The rates of adverse events were also similar -- 18.1% for rifampin versus 22.6% for rifapentine -- and 2.8% of rifampin patients reported hepatitis compared with 3.6% of rifapentine patients.
It remains unclear why the expected difference did not materialize, Dorman said, adding that it could be a function of dosing levels or perhaps the fact that both drugs were taken without food.
She noted that the proportion of culture conversions is a surrogate marker for the sterilizing activity of the drugs which may not have been a good reflection of that activity.
The study was supported by the CDC. Study drugs were donated by sanofi-aventis. Dorman said she had no conflicts.
Source reference: Dorman S, et al "A phase II study of a rifapentine-containing regimen for intensive phase treatment of pulmonary tuberculosis: Preliminary results for tuberculosis trials consortium study 29" Am J Respir Crit Care Med 2011; 183: A6413.
http://www.medpagetoday.com/MeetingCoverage/ATS/26575
TUBERCULOSIS: Simplifying treatment for TB without symptoms
May 16 2011
The findings of a large government trial show a treatment regimen that differs from the standard therapy may be effective in treating the latent form of tuberculosis.
About 11 million people in the U.S. are infected with latent tuberculosis, which is symptom-free and is not contagious. Of those, 5 to 10 percent will go on to develop active TB, which can be spread to others and can be fatal if not properly treated.
Researchers looked at 8,000 people with latent TB, mostly in the United States or Canada. They were randomly given one of two treatments- the standard course of therapy, which takes nine months of daily treatment, or a once-weekly treatment for three months. The standard treatment is isoniazid. The experimental regimen combined isoniazid with rifapentine.
"The treatment of latent TB can be shortened from 270 doses to 12 doses, and be just as effective- that's pretty impressive," said Dr. Dean Schraufnagel, president of the American Thoracic Society and a TB expert.
Those on the once-weekly treatment were more likely to complete it- 82% versus the current rate of 69%.
"This new treatment for TB may have great, extraordinary consequences," Schraufnagel said. "I believe this will be a major strategy to control TB, both in the U.S. and worldwide."
Statistics from the CDC show the case count is on the decline, but in 2007, 544 deaths occurred from TB. In 2009, the case numbers were at an all-time low. Asians, African Americans and Native Hawaiians, along with foreign-born individuals, are disproportionately affected more than whites.
“Achieving CDC's goal of TB elimination in the United States means not only treating those individuals who already have TB disease, but also treating those with latent TB infection who are at high risk of developing TB disease and potentially transmitting it to others,” said Dr. Kevin Fenton, Director of CDC’s National Center for HIV-AIDS, Viral Hepatitis, STD and TB Prevention (NCHHSTP).
“While the number of reported cases of TB disease is currently low, in today's highly interconnected world, we need to guard against a resurgence of TB both at home and abroad,” he added.
Symptoms of TB can include chest pain, a bad cough (possibly with blood), weakness and a fever. While TB usually impacts the lungs, the kidneys, brain and spine may also be affected.
Schraufnagel said people with latent TB who go on to develop active TB won't know it at first.
"They'll develop a little cough- the cough persists," he said. "They think it might be a cold, sometimes they might have a little fever. This cough doesn't go away and after a month or two months, or three months, they may contact a doctor. And even then, they're often treated for a cold or some other thing. Then they would get an X-ray or examine the sputum and make the diagnosis of TB. By that time, those people have infected 10, 20, 30, 40, a lot of new people."
The CDC offers these guidelines as to who should get tested for TB:
- If you've been around someone with active TB disease
- If you have HIV or another condition that makes the immune system weaker
- If you live in a homeless shelter or some nursing homes
- If you are from a country where TB is very common
- If you inject illegal drugs
One-third of the world's total population are infected with TB bacteria, according to the World Health Organization.
It says each person who becomes sick with active TB, if not treated, can infect on average 10 to 15 other people a year.
"It's important to note that the study was conducted in countries which carry a low to medium incidence of tuberculosis,” said Dr. Kenneth Castro, Director, Division of Tuberculosis Elimination, NCHHSTP. "That is primarily in the United States and Canada, and the results can therefore only be applied to these settings. The trial did not include countries with high tuberculosis incidence where the increased risk of re-infection could affect the effectiveness of this regimen."
http://thechart.blogs.cnn.com/2011/05/16/simplifying-treatment-for-tb-without-symptoms/
TUBERCULOSIS: Shorter treatment found for latent tuberculosis (Priftin - Rifapentine)
Thomas H. Maugh II, Los Angeles Times thomas.maugh@latimes.com
May 17, 2011
A cocktail of antibiotics taken for three months works as well as the standard nine-month TB treatment, researchers say. That increases the proportion of people who finish treatment, helping stop the spread of TB.
In what is being hailed as the biggest breakthrough since the 1960s in treatment for latent tuberculosis — noninfectious TB without symptoms — researchers said Monday that weekly doses of a cocktail of antibiotics can cure the infection in only three months as effectively as the standard treatment of daily drugs for nine months.
By reducing the number of pills and shortening the time required for therapy, the new regimen increased the proportion of patients who completed treatment from 69% to 82%. By increasing the success rate of therapy, the regimen should reduce spread of the disease and the risk of inducing resistance to TB drugs, experts said.
"It's very clear that, in this country, if we are going to get rid of TB, we have to do so by preventing people at risk from going on to develop the disease," said Dr. Richard Chaisson of the Johns Hopkins University School of Medicine, the senior author of the study. That can only be accomplished by curing latent TB, he said.
Latent TB refers to infection by the TB bacterium in people who do not have symptoms and cannot infect others. But that latent infection can be converted into an active one by many different factors — at which point the patient becomes infectious.
Although TB control measures in the United States have brought the incidence of the disease to an all-time low of 11,181 cases in 2010, it is estimated that at least 11 million Americans have latent TB.
"The 11 million Americans with latent TB represent a ticking time bomb," Dr. Kenneth Castro, director of the Centers for Disease Control and Prevention's division of tuberculosis elimination, said at a news conference Monday. "They're the source of future TB cases."
Daily doses of the antibiotic isoniazid have been the standard of care for TB for nearly 60 years. But a newer, more potent drug, rifapentine, marketed under the brand name Priftin by Sanofi-Aventis, persists in the body for long periods.
In the study, begun 10 years ago, researchers enrolled 8,053 people with latent TB, most living in the U.S. and Canada, though some were in Brazil and Spain. Half were selected to receive conventional daily isoniazid treatment for nine months and half received a combination of isoniazid and rifapentine weekly for 12 weeks.
In the 33 months of follow-up, seven of those receiving the combination therapy developed TB, compared with 15 of those receiving isoniazid alone, coauthor Dr. Timothy Sterling of Vanderbilt University reported at the American Thoracic Society International Conference in Denver.
The combination "works certainly as well as isoniazid, and actually a little bit better," Chaisson said.
One complication is that the treatment cannot be given simultaneously with drugs for HIV infections, a significant drawback because many patients in the developing world have both diseases. Rifapentine stimulates the production of liver enzymes that break down many drugs, including protease inhibitors used for HIV treatment. The enzymes reduce levels of the drugs by as much as 95%, making use of the drugs at the same time pointless.
Chaisson said the team was now testing a regimen in which protease inhibitor treatment is halted for a month and rifapentine given daily. Normal HIV treatment is then resumed. Results from that study should be published soon.
The trial was sponsored by the CDC, and results have been submitted for publication.
http://www.latimes.com/health/la-he-latent-tb-20110517,0,2486639.story
May 17, 2011
A cocktail of antibiotics taken for three months works as well as the standard nine-month TB treatment, researchers say. That increases the proportion of people who finish treatment, helping stop the spread of TB.
In what is being hailed as the biggest breakthrough since the 1960s in treatment for latent tuberculosis — noninfectious TB without symptoms — researchers said Monday that weekly doses of a cocktail of antibiotics can cure the infection in only three months as effectively as the standard treatment of daily drugs for nine months.
By reducing the number of pills and shortening the time required for therapy, the new regimen increased the proportion of patients who completed treatment from 69% to 82%. By increasing the success rate of therapy, the regimen should reduce spread of the disease and the risk of inducing resistance to TB drugs, experts said.
"It's very clear that, in this country, if we are going to get rid of TB, we have to do so by preventing people at risk from going on to develop the disease," said Dr. Richard Chaisson of the Johns Hopkins University School of Medicine, the senior author of the study. That can only be accomplished by curing latent TB, he said.
Latent TB refers to infection by the TB bacterium in people who do not have symptoms and cannot infect others. But that latent infection can be converted into an active one by many different factors — at which point the patient becomes infectious.
Although TB control measures in the United States have brought the incidence of the disease to an all-time low of 11,181 cases in 2010, it is estimated that at least 11 million Americans have latent TB.
"The 11 million Americans with latent TB represent a ticking time bomb," Dr. Kenneth Castro, director of the Centers for Disease Control and Prevention's division of tuberculosis elimination, said at a news conference Monday. "They're the source of future TB cases."
Daily doses of the antibiotic isoniazid have been the standard of care for TB for nearly 60 years. But a newer, more potent drug, rifapentine, marketed under the brand name Priftin by Sanofi-Aventis, persists in the body for long periods.
In the study, begun 10 years ago, researchers enrolled 8,053 people with latent TB, most living in the U.S. and Canada, though some were in Brazil and Spain. Half were selected to receive conventional daily isoniazid treatment for nine months and half received a combination of isoniazid and rifapentine weekly for 12 weeks.
In the 33 months of follow-up, seven of those receiving the combination therapy developed TB, compared with 15 of those receiving isoniazid alone, coauthor Dr. Timothy Sterling of Vanderbilt University reported at the American Thoracic Society International Conference in Denver.
The combination "works certainly as well as isoniazid, and actually a little bit better," Chaisson said.
One complication is that the treatment cannot be given simultaneously with drugs for HIV infections, a significant drawback because many patients in the developing world have both diseases. Rifapentine stimulates the production of liver enzymes that break down many drugs, including protease inhibitors used for HIV treatment. The enzymes reduce levels of the drugs by as much as 95%, making use of the drugs at the same time pointless.
Chaisson said the team was now testing a regimen in which protease inhibitor treatment is halted for a month and rifapentine given daily. Normal HIV treatment is then resumed. Results from that study should be published soon.
The trial was sponsored by the CDC, and results have been submitted for publication.
http://www.latimes.com/health/la-he-latent-tb-20110517,0,2486639.story
Tuesday, 20 July 2010
TUBERCULOSIS: Rifapentine is granted Orphan Drug Status
July 1, 2010 – Shorter treatment duration with rifapentine expected to bring
significant benefits to patients -
Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that the European Commission has granted Orphan Drug status for rifapentine for the treatment of tuberculosis (TB). Rifapentine is an antibiotic member of the rifamycin class, with a higher inhibitory activity against Mycobacterium tuberculosis and a longer half-life than rifampin, the cornerstone of current
TB treatment regimen. These combined are expected to improve the drug exposure of patients to the drug and potentially lead to better efficacy.
European Orphan Drug designation is granted to medicines intended for treatment of life-threatening or chronically debilitating pathologies that affect no more than 5 in 10,000 people in the European Community. The European Commission’s decision follows the positive opinion released by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) that a rifapentine-based combination regimen may be of significant clinical benefit for drug-susceptible TB patients by shortening their tuberculosis treatment.
“Rifapentine is currently one of the most promising drugs for the improvement of patient compliance, which is key to the success of tuberculosis treatment,” said Robert Sebbag, Vice President, Access to Medicines, sanofi-aventis. “To avoid as much as possible the emergence of resistant strains, it is of utmost importance to simplify the treatment of non-resistant TB.”
Sanofi-aventis is revisiting the development of rifapentine to be given daily, in combination with standard daily companion drugs, with the objective of significantly shortening the duration of drug-susceptible TB treatment. This should lead to less premature cessations of treatment, and thus to a reduction of
treatment failures, a lesser risk of development of drug-resistance, as well as a reduction of costs, all of which are expected to bring significant benefits to patients and public health systems.
Rifapentine is currently marketed in the United States for the treatment of pulmonary and drugsusceptible TB within a standard 6-month course combination regimen.
http://en.sanofi-aventis.com/binaries/20100701_RIFAPENTINE_en_tcm28-28921.pdf
significant benefits to patients -
Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that the European Commission has granted Orphan Drug status for rifapentine for the treatment of tuberculosis (TB). Rifapentine is an antibiotic member of the rifamycin class, with a higher inhibitory activity against Mycobacterium tuberculosis and a longer half-life than rifampin, the cornerstone of current
TB treatment regimen. These combined are expected to improve the drug exposure of patients to the drug and potentially lead to better efficacy.
European Orphan Drug designation is granted to medicines intended for treatment of life-threatening or chronically debilitating pathologies that affect no more than 5 in 10,000 people in the European Community. The European Commission’s decision follows the positive opinion released by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) that a rifapentine-based combination regimen may be of significant clinical benefit for drug-susceptible TB patients by shortening their tuberculosis treatment.
“Rifapentine is currently one of the most promising drugs for the improvement of patient compliance, which is key to the success of tuberculosis treatment,” said Robert Sebbag, Vice President, Access to Medicines, sanofi-aventis. “To avoid as much as possible the emergence of resistant strains, it is of utmost importance to simplify the treatment of non-resistant TB.”
Sanofi-aventis is revisiting the development of rifapentine to be given daily, in combination with standard daily companion drugs, with the objective of significantly shortening the duration of drug-susceptible TB treatment. This should lead to less premature cessations of treatment, and thus to a reduction of
treatment failures, a lesser risk of development of drug-resistance, as well as a reduction of costs, all of which are expected to bring significant benefits to patients and public health systems.
Rifapentine is currently marketed in the United States for the treatment of pulmonary and drugsusceptible TB within a standard 6-month course combination regimen.
http://en.sanofi-aventis.com/binaries/20100701_RIFAPENTINE_en_tcm28-28921.pdf
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