"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, which 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.
Vasculitis, an inflammation of the blood vessels, can damage tissues and organs and, in severe cases, lead to death. Specifically, the study examined something known as ANCA-associated vasculitis that includes Wegener's granulomatosis and microscopic polyangiitis. "The reason this is such a significant study is that this is an uncommon but devastating group of diseases," said Dr. Spiera. Prior to the use of cyclophosphamide treatment, 70 percent of patients who were diagnosed with severe forms of ANCA-associated vasculitis could be expected to be dead within three years. In the 1970s, doctors discovered that cyclophosphamide was extremely effective at combating the disease and could put people into remission. In the ensuing decades, however, doctors recognized that these drugs came with a price.
"If you followed patients long enough, you found they had a higher risk of leukemias, lymphomas and solid tumors," said Dr. Spiera, who is also an Associate Professor at Weill Cornell Medical College. "People would sometimes develop terrible infections. Women, almost reliably, would become infertile, as did many men. So, although it was a dramatically effective drug at reducing remissions in these patients, it came at a price."
In the current study, nine centers enrolled a total of 197 patients with severe Wegener's granulomatosis or microscopic polyangiitis, two of the more common types of ANCA-associated vasculitis. Patients were given steroids and randomized to receive either the standard treatment with cyclophosphamide or Rituxan given at a dose of 375 mg/m2 weekly for four weeks. Investigators used the standard tools to assess disease status and remission. The study was rigorously designed and was double-blinded, meaning that neither patient nor doctor knew which drug individuals were getting.
At the time of the data analysis, 84 of the 99 (85%) patients in the Rituxan arm and 81 of the 98 patients (83%) in the cyclophosphamide arm had completed six months of follow-up. Investigators found that the treatments were equally effective in putting patients into remission and that, in fact, the treatment outcomes looked slightly better in patients receiving Rituxan (64% vs. 55%). This difference, however, was not considered statistically significant (P=0.21).
"These results show that the Rituxan worked at least as well as cyclophosphamide," Dr. Spiera said. "If anything, there was almost a hint of it maybe looking a little better, and even in the short term, it looked safer in some respects. This study shows that there is strong evidence that Rituxan may be an alternative to cyclophosphamide in this disease. It might help manage flares in patients who have gone into remission, and it could be a consideration as first-line therapy, especially in women of child bearing potential who have a good chance of losing their fertility if treated with cyclophosphamide."
Until this study, there was only anecdotal evidence that Rituxan would be beneficial in patients with vasculitis. ANCA-associated vasculitis is one of the few rheumatic diseases that is equally represented in men and women. It can occur in people of all ages. Rituxan, manufactured by Genentech, is currently approved in the U.S. to treat non-Hodgkin's lymphoma and rheumatoid arthritis.
The study was funded by the National Institutes of Health (specifically the Immune Tolerance Network through the National Institute of Allergy and Infectious Diseases). Biogen-Idec partially supported the trial as well. In addition to the Mayo Clinic and Hospital for Special Surgery, study investigators hailed from Massachusetts General Hospital in Boston; Johns Hopkins in Baltimore; Cleveland Clinic; University Medical Center Groningen in the Netherlands; Duke University Medical Center; University of Alabama at Birmingham; Immune Tolerance Network in San Francisco; National Institutes of Health in Bethesda, Maryland; Rho in Chapel Hill, N.C.; PPD of Wilmington, N.C.; and Genentech.
About Hospital for Special Surgery
Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopedics, rheumatology and rehabilitation. HSS is nationally ranked No. 2 in orthopedics, No. 3 in rheumatology and No. 24 in neurology by U.S. News & World Report (2009), and has received Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center. In 2008 and 2007, HSS was a recipient of the HealthGrades Joint Replacement Excellence Award. A member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College, HSS provides orthopedic and rheumatologic patient care at New York-Presbyterian Hospital at New York Weill Cornell Medical Center. All Hospital for Special Surgery medical staff are on the faculty of Weill Cornell Medical College. The hospital's research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at www.hss.edu.
Phyllis Fisher | EurekAlert!
Penn studies find promise for innovations in liquid biopsies
30.03.2017 | University of Pennsylvania School of Medicine
'On-off switch' brings researchers a step closer to potential HIV vaccine
30.03.2017 | University of Nebraska-Lincoln
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering