Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Therapy for severe vasculitis shows long-term effectiveness

01.08.2013
NIH-funded study finds that rituximab is as effective as standard therapy, requires shorter treatment duration

Administering the drug rituximab once weekly for one month provides the same benefits as 18 months of daily immunosuppressive therapy in people with severe forms of vasculitis, or inflammation of the blood vessels, a study has found.

Researchers from the Immune Tolerance Network (ITN), an international clinical trials group funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), found that rituximab is as effective as the standard therapy at inducing and maintaining disease remission. The findings appear in the August 1 issue of the New England Journal of Medicine.

In addition to these important results, the online version of the study is the first to contain direct links to TrialShare (https://www.itntrialshare.org/), a new data analysis and sharing portal developed and managed by the ITN. The website provides access to the study's raw data and statistical analyses, allowing researchers to re-analyze the data and develop new hypotheses. As of this writing, TrialShare houses data from eight ITN clinical studies.

The current trial included participants with severe granulomatosis with polyangiitis, formerly known as Wegener's granulomatosis, and microscopic polyangiitis. In the United States, approximately 6,000 people are diagnosed with these diseases each year. Those who suffer from these rare autoimmune diseases—termed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides—produce antibodies that attack immune cells called neutrophils, causing inflammation in small- to medium-sized blood vessels. This leads to potentially life-threatening organ damage, particularly in the airways, lungs and kidneys. The current standard of care, developed four decades ago by NIAID Director Anthony S. Fauci, M.D., and colleagues and subsequently modified by other investigators, involves a three- to six-month course of daily cyclophosphamide plus steroids, followed by daily azathioprine. This drug regimen has turned these once-fatal diseases into chronic conditions in which most people can achieve remission, although relapse is common.

"This new treatment strategy to help patients with ANCA-associated vasculitides achieve and maintain lasting remission is a long-awaited development," said Dr. Fauci. "In addition, we welcome the use of TrialShare to share data derived from publicly funded research to increase transparency, facilitate collaboration among scientists and accelerate the pace of discovery."

Rituximab depletes the body's supply of cells thought to be responsible for ANCA production. Rituximab is a more targeted approach than the current standard of care, which involves nonspecific immunosuppression with potentially severe side effects.

To test the drug's safety and effectiveness in people with these diseases, ITN investigators led by Ulrich Specks, M.D., of the Mayo Clinic, Rochester, Minn., and John Stone, M.D., M.P.H., of Massachusetts General Hospital, Boston, randomly divided 197 trial participants into two groups. One group received intravenous rituximab once weekly for one month. The other received standard care of three to six months of daily treatment with cyclophosphamide, followed by daily doses of azathioprine. Both groups received placebos, and all trial participants followed the same steroid treatment regimen. The steroid dose was gradually decreased, and those who went into remission stopped receiving steroids after six months.

In 2010, the investigators reported that, after six months, 64 percent of those who received rituximab had no signs of disease activity, compared to 53 percent of those given standard care. Based on these results, the Food and Drug Administration in April 2011 approved rituximab in combination with steroids for the treatment of granulomatosis with polyangiitis and microscopic polyangiitis. Rituximab also is FDA-approved for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis.

In the current study, the researchers followed trial participants for an additional year to evaluate rituximab's long-term efficacy and safety. After 18 months, rituximab continued to be as effective as the standard regimen, with 39 percent of participants who received rituximab and 33 percent of those who received standard care showing no signs of active disease. There were no major differences between the two groups in average length of remission or in the frequency and severity of relapses. Adverse events, such as infection, occurred at a similar rate in both groups during the 18 months.

"Notably, rituximab patients who achieved remission within six months received no additional immunosuppression for more than one year," said Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology and Transplantation. "Reducing the need for immunosuppressive drugs is of great benefit to the patient, lessening the risk of possible serious long-term side effects such as cancer, infertility and infection."

For the 101 people who entered the trial with relapsing disease, rituximab was initially more effective than standard therapy at inducing and maintaining remission. After 12 months, 49 percent of those who received rituximab remained free of disease activity, compared to 24 percent of those given standard therapy. After 18 months, the researchers found that the relapse rate remained lower in the rituximab group, but the difference was not statistically significant.

Most people treated for ANCA-associated vasculitides eventually relapse, regardless of whether they receive rituximab or cyclophosphamide-based therapy. "The risk of relapse following treatment-induced remission is a reality of these chronic autoimmune diseases," said Dr. Specks. "The data from this trial suggest that intermittent retreatment with rituximab could be a more effective approach to long-term disease control than daily immunosuppression for patients who are at a high risk for relapse."

The ITN conducted this work under NIH contract number N01AI15416. Genentech and Biogen Idec also provided partial financial support. Additional support was provided to individual investigators and clinical sites by the National Center for Advancing Translational Sciences and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, components of NIH, and by the Arthritis Foundation. The ClinicalTrials.gov identifier for the study Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis (RAVE) is NCT00104299. (http://www.clinicaltrials.gov/ct2/show/NCT00104299)

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH...Turning Discovery Into Health®

References:
U Specks et al. Efficacy of remission induction regimens for ANCA-associated vasculitis. New England Journal of Medicine DOI: 10.1056/NEJMoa1213277 (2013).

JH Stone et al. Rituximab versus cyclophosphamide for induction of remission in ANCA-associated vasculitis. New England Journal of Medicine DOI: 10.1056/NEJMoa0909905 (2010).

Hillary Hoffman | EurekAlert!
Further information:
http://www.niaid.nih.gov
http://www.nih.gov

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>