Advances in genetics related to ankylosing spondylitis

Sun, 10 Jan 2010 14:50:26 PST

( from http://www.rxpgnews.com ) Work done in part by researchers at The University of Texas Health Science Center at Houston has led to the discovery of two new genes that are implicated in ankylosing spondylitis (AS), an inflammatory and potentially disabling disease. In addition, the international research team pinpointed two areas along stretches of DNA that play an important role in regulating gene activity associated with the arthritic condition.

The findings, a critical milestone in the understanding of AS, are published in the January issue of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases. "This helps us better understand what is driving this disease and gives us direction for new treatments and diagnostic tests," said John D. Reveille, M.D., the study's principal investigator and professor and director of the Division of Rheumatology and Clinical Immunogenetics at The University of Texas Medical School at Houston.

Reveille, the university's Linda and Ronny Finger Foundation Distinguished Chair in Neuroimmunologic Disorders, and Matthew A. Brown, M.D., professor of immunogenetics at Australia's University of Queensland, led the research by the Triple "A" Spondylitis Consortium Genetic Study (i.e. the TASC or Australo-Anglo-American Spondylitis Consortium). Based on work from a genome-wide association scan, the team identified genes ANTXR2 and IL1R2 as well as two gene deserts, segments of DNA between genes on chromosomes 2 and 21 that are associated with ankylosing spondylitis. Importantly, the study also confirmed the Triple "A" Australo-Anglo-American Spondylitis Consortium's previously reported associations of genes IL23R and ERAP1, formerly known as ARTS1.

Reveille, chief of rheumatology at Memorial Hermann-Texas Medical Center, said the genetic discoveries bring the scientific community closer to fully understanding AS, a chronic form of arthritis that attacks the spine and also can target other joints and organs in the body. The Centers for Disease Control and Prevention for the National Arthritis Data Workgroup estimates that AS and its related diseases affect as many as 2.4 million people in the United States. It generally strikes patients in their teens, 20s or 30s and can cause a complete fusion of the spine, leaving patients unable to straighten and bend.

Steve Haskew, who has lived with AS for more than three decades, said these genetic discoveries offer hope to patients, especially those newly diagnosed.

"When I first started experiencing lower back pain and the aching joints, no one could tell me what was wrong," said Haskew, co-leader of an AS support group. "It's fascinating to see how far we've come and how much has been learned about the disease."

Laurie Savage, co-principal investigator and executive director of the Spondylitis Association of America (SAA) said, "These new breakthroughs are, indeed, good news for those whom we serve. It is very encouraging to know that the health impact and economic consequences of spondyloarthritis in the world eventually will be contained as a direct consequence of the dedication of Drs. Reveille, Brown and colleagues, and that of the many individuals affected by spondyloarthritis who have participated in these studies."

Continuous NSAID use beneficial in ankylosing spondylitis

Thu, 02 Jun 2005 15:48:38 PST

( from http://www.rxpgnews.com ) A widely under-recognized form of arthritis, ankylosing spondylitis (AS) is a chronic, progressive disease targeting the spine. Commonly striking in young adulthood, before age 35, AS causes inflammation, pain, and stiffness in the spinal joints--the vertebrae--and the sacroiliac joint, where the spinal column meets the pelvis. In advanced cases, this disease can result in deforming, crippling spinal fusion and organ damage. According to expert estimates, AS afflicts at least half a million people in the United States.

While there is no cure for AS, numerous studies have affirmed the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for improving physical function, as well as providing rapid relief from back pain and stiffness. Yet, physicians generally recommend taking NSAIDs on a short-term basis, only as needed for severe AS symptoms, due to the risk of gastrointestinal complications associated with long-term use. Inspired by the improved gastoprotective safety profile of COX-2-selective NSAIDs, an international team of rheumatologists set out to explore the impact of ongoing NSAID treatment, over a 2-year span, on the course of AS. Featured in the June 2005 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), their study offers hope for decreasing the progression of AS, without increasing the risk of peptic ulcers or other adverse events.

The clinical trial began with 215 outpatients, drawn from the records of 76 hospitals and private practices in France, with a history of AS. Using a computer-generated randomization list, the patients were divided into two treatment groups. The first group, comprised of 111 patients, was prescribed twice-daily treatment with a NSAID, regardless of symptoms. The second group, comprised of 104 patients, was also prescribed a NSAID, but instructed to take it only when they suffered pronounced pain or stiffness. Both groups started treatment with celecoxib at a dosage of 100 milligrams. All patients were allowed to increase their dosage to 200 milligrams, if necessary, or switch to another NSAID, as long as they maintained their assigned treatment strategy--either continuous or on-demand. Compliance was assessed by pill count.

At baseline, after 1 month, at 7 follow-up visits conducted at 3-month intervals, and at the final visit, patients in both groups were thoroughly evaluated, through questionnaires and laboratory tests, for clinical signs and symptoms of AS, as well as for any adverse events. X-rays of the spine were taken at the study's onset and 24-month culmination.

Overall, differences in hallmarks of disease activity--including spinal pain, night pain, morning stiffness, fatigue, and restricted mobility--were not statistically significant between the two treatment groups. There were also no significant differences in the gastrointestinal, respiratory, cardiovascular, and other health problems experienced by the groups, with the exception of symptoms of depression, which occurred more frequently in the continuous-treatment group. Only a single adverse event--a case of severe abdominal pain requiring hospital admission in the on-demand group--was deemed directly related to NSAID use, by the treating physician. There were, however, statistically significant differences in the X-ray evidence of AS progression between the continuous-treatment and the on-demand groups.

Complete sets of radiographs were available for 76 of the patients in the continuous-treatment group and for 74 of the patients in the on-demand group. Scored by a single observer blinded to treatment strategy, using the modified Stoke Ankylosing Spondylitis Spine Score (SASS), the X-rays showed both more pronounced disease progression and in a greater proportion of patients among patients who had taken NSAIDs only as needed for pain management. In fact, twice as many patients in the on-demand group were scored as having moderate to high levels of spinal joint damage at the 2-year mark than patients in the continuous-treatment group. The between-group difference in radiographic progression remained stable and significant after adjusting for baseline values of joint damage and disease-activity variables.

As noted by Professors Maxime Dougados and Desiree van der Heijde, the study's leading authors and participating rheumatologists, the findings have implications for both the treatment of AS and the application of NSAIDs. On the strength of the data, inflammation and progression of joint damage may be two separate processes in AS, which may be different from the situation in rheumatoid arthritis. And NSAIDs, generally considered symptom modifiers, may have unexplored disease-controlling properties.

"We conclude that a strategy of continuous use of NSAIDs decreases the radiographic progression in patients with AS without substantially increasing toxicity," Prof. Dougados states. "While awaiting confirmation of these results, we carefully recommend that if patients need treatment with NSAIDs to reduce the signs and symptoms of AS, they should take NSAIDs continuously instead of as needed based on symptoms."

RxPG News : Ankylosing Spondylitis

Advances in genetics related to ankylosing spondylitis

Continuous NSAID use beneficial in ankylosing spondylitis