The Cleveland Clinic Board of Governors recognized that patients with vasculitis were profoundly underserved and an organized multidisciplinary approach was required for meaningful progress to occur. As a result, in 1999, The Center for Vasculitis Care and Research was established within the Department of Rheumatic and Immunologic Diseases. Together with the Harold C. Schott (HCS) Foundation, an endowed Chair was established to better ensure that vasculitis research would forever be part of the medical culture of Cleveland Clinic. Dr. Gary Hoffman, the former Director of Vasculitis and Related Disease Research at the National Institutes of Health (NIH) was the first recipient of the HCS Chair.
Since its inception, the Center for Vasculitis Care and Research has been at the forefront of many important initiatives involving patient care, research, and education. As vasculitis is a complex and uncommon disease process, the development of collaborations with physicians, scientists, and skilled investigators from many different disciplines has been invaluable in formulating concepts that have lead to important advancements in knowledge.
The first organized network that firmly established the ability of investigators to conduct large scale clinical trials in vasculitic disease was the International Network for the Study of Systemic Vasculitides (INSSYS). The Network was founded by Dr. Hoffman. The Network infrastructure was moved from the NIH to Cleveland Clinic when he arrived in 1992. During the ensuing years, the membership of The Network grew from 15 to 55 institutions that are located throughout the world. INSSYS has conducted a number of multicenter studies since its inception including the evaluation of methotrexate in the treatment of giant cell arthritis and studies of blood test “markers” of vascular injury. Most recently, INSSYS centers in the United States conducted the first randomized, controlled, multicenter trial in any vasculitic disease examining the utility of the medication etanercept in Wegener’s granulomatosis (WGET). In 2002, Dr. Hoffman selected Dr. John Stone of Johns Hopkins University, who had been the Principal Investigator of the etanercept trial, to continue the mission of INSSYS as its Chairman. INSSYS is an important means of facilitating collaborative studies in which The Center for Vasculitis Care and Research remains a prominent and active participant.
An exciting recent initiative that will even further increase the ability to conduct collaborative studies has been the establishment of the Vasculitis Clinical Research Consortium (VCRC). This consortium involves 4 major United States vasculitis centers and several domestic and foreign secondary centers. These 4 centers include Boston University (Dr. Peter Merkel is the Principal Investigator of the VCRC), Johns Hopkins Medical Center (Dr. John H. Stone), the Mayo Clinic (Dr. Ulrich Specks and Dr. Eric Matteson), and the Center for Vasculitis Care and Research at The Cleveland Clinic. The VCRC is funded through the Rare Diseases Clinical Research Network, National Institutes of Health. The VCRC is establishing longitudinal protocols that involve large numbers of patients with vasculitis. These studies will allow investigators to better understand the course of these illnesses and provide a means of examining markers of disease activity. In addition, the VCRC is establishing an important foundation for the conduct of future trials of new medications.
A critical aspect of the VCRC is a dedicated fellowship that will provide training for new investigators in vasculitis. This alone, however, will not meet the needs of our national and international goal of providing adequate expertise for our vasculitis patients or adequate numbers of investigators to work towards improved understanding, better treatment and cures of vasculitis. Cleveland Clinic's Department of Rheumatic and Immunologic Diseases and The Center for Vasculitis Care and Research has also been instrumental in training clinician-investigators since 1992. Apart from visiting faculty from other American institutions, doctors from Brazil, Mexico, Canada and Singapore have improved their knowledge of vasculitis at Cleveland Clinic and returned home able to offer services that had previously been absent. Our commitment to this program will continue and grow in the future.
The Center for Vasculitis Care and Research is one of 8 medical centers collaborating in a large scale randomized clinical trial that will examine the use of a medication called rituximab in treating ANCA-associated vasculitis (RAVE). Dr. Ulrich Specks from the Mayo Clinic and Dr. John Stone from Johns Hopkins will serve as co-Principal Investigators for this study. The study is funded by the National Institutes of Health through the Immune Tolerance Network (ITN).
A clinical trial that Drs. Karen Rendt and Gary Hoffman, of The Center for Vasculitis Care and Research, are leading a study exploring the therapeutic use of the medication infliximab in giant cell arthritis. This study is supported by Centocor, Inc.
The care of people with vasculitis at the Center has provided a tremendous wealth of experience from which important knowledge may be gained. Through support from the Wegener’s Granulomatosis Association, Drs. Alexandra-Villa-Forte and Gary Hoffman are examining how the use of short term cyclophosphamide followed by less toxic maintenance therapies has impacted the outcome of people with Wegener’s granulomatosis.
The Center for Vasculitis Care and Research seeks to grow more effectively in linking basic science in the laboratory to solving clinical problems. The importance and potential insights gained from such work has been already exemplified by the initiatives that have been undertaken.
Drs. Rula Hajj-Ali, Gary Hoffman and Thomas Hamilton have been actively investigating the immunology of the blood vessel wall with the goal of trying to identify mechanisms that may be involved in the development of vasculitis. These studies have focused on the analysis of tissue from temporal artery biopsies that were obtained to establish a diagnosis of giant cell arteritis. Such work could lead to a better understanding of the causes of this, and other vasculitic diseases.
Assessing disease activity remains one of the most challenging problems that physicians face in the care of patients with vasculitis. Identification of markers of disease activity would represent a major advancement in patient care and may provide critical insights into disease mechanisms. Drs. Gary Hoffman, Stanley Hazen and Marie-Luise Brennan have sought to explore surrogate markers in the vasculitic diseases.
Although vasculitis is uncommonly seen in members of the same family, whether there is hereditary basis for vasculitis has remained an important question that is of great interest to both patients and investigators. As technology and medicine have become more advanced, the study of hereditary factors, which is called genetics, has grown dramatically. In conjunction with the WGET trial, the Center for Vasculitis Care and Research participated in the establishment of a repository at the University of Alabama (WGGER) that will contain genetic material (also called DNA) from 500 people with Wegener’s granulomatosis as well as from 1000 healthy individuals. As the frontiers of science continue to expand, this repository will provide an invaluable resource through which to conduct future genetic studies.
Partnerships with experts in blood vessel imaging have led to studies that could have never been performed by sub-specialists working in the isolation of their own areas of expertise. Together with Drs. Richard White and Scott Flamm, rheumatologists demonstrated both the strengths and limitations of magnetic resonance (MR) imaging in the evaluation of inflammation affecting the large blood vessels.
The Center for Vasculitis Care and Research has always appreciated the impact that vasculitis has on patients and their families. Dr. Hoffman and collaborators at the National Institutes of Health conducted one of the first studies of epidemiological patterns of vasculitis and the socioeconomic impact of these diseases. In continuing to explore factors that affect the quality of life in people with giant cell arteritis, Tiffany Clark, C.N.P. is participating in a study with Dr. David Hellman from Johns Hopkins Medical Center to examine this important area.
Cleveland Clinic's Department of Rheumatic and Immunologic Diseases is also committed to the care of patients with central nervous system (CNS, or brain) vasculitis. The Department Vice Chairman, Dr. Leonard Calabrese, is among the most recognized experts in CNS vasculitis in the world. He has elucidated the heterogeneity of this group of illnesses, and established working guidelines to provide more effective care for subsets of patients with these disorders. Dr. Calabrese is also recognized for his work in vasculitis complicating viral diseases, particularly HIV and hepatitis. He is an authority in the general area of vasculitis as well.
An infrastructure of research nurses has been essential to carrying out the daily patient care and administrative functions inherent to multicenter investigation. They have facilitated research studies in the department for over 25 years. These individuals have been an important resource and are critical to our continued success. The research nurses have been supported by profits from studies of pharmaceutical agents in diseases other than vasculitis. Maintaining this infrastructure depends on the success of the department in continuing to obtain Federal grants and performing studies that are co-ventured with the pharmaceutical and biological products industries.
A number of collaborators provide essential services, without which the study and care of patients with vasculitis would not be possible. These include Dr. Richard White (magnetic resonance imaging, with particular application to vasculitic diseases), Dr. Robert Lorenz (Otolaryngology), Dr. Richard Prayson (Department of Anatomic Pathology), and Drs. Michael Lee, Victor Perez and Greg Kosmorsky (Ophthalmology). Our Department of Cardiothoracic Surgery is among the most highly regarded in the world. They have identified, among patients referred for surgical procedures, young women with vasculitis affecting heart valves and the aorta. These patients require immunosuppressive therapy and are therefore cared for by both our vasculitis group and the surgical staff.
The complexity of vasculitic diseases requires a team approach, such as that provided at Cleveland Clinic. The rarity of these diseases also requires a multicenter collaborative approach that allows investigators to share information and recruit patients for studies so that adequate numbers will permit definitive conclusions, rather than crude speculation.
The Cleveland Clinic Department of Rheumatic and Immunologic Diseases has been recognized for its clinical expertise in providing care and performing clinical research in patients with a broad range of vasculitic diseases. These include giant cell arteritis, Takayasu’s arteritis, Wegener’s granulomatosis, central nervous system vasculitis, Churg-Strauss syndrome, polyarteritis nodosa, cutaneous vasculitis, pediatric vasculitis, and viral-associated vasculitic conditions.
December 7, 2004
