PHILADELPHIA, Sept. 1-As if inflammatory bowel disease isn't enough, it seems that patients with IBD may be prone to demyelinating diseases such as multiple sclerosis, and to other inflammatory conditions such as arthritis and asthma.
Researchers at the University of Pennsylvania here looked at records of nearly 8,000 patients with Crohn's disease, and more than 12,000 with ulcerative colitis, and found that the rate of MS, optic neuritis, or demyelination was about 2.5 times greater among patients with IBD compared with controls.
Action Points
- Monitor patients with IBD who are receiving TNFα blockers such as Enbrel, Humira, or Remicade for signs of possible co-morbid conditions such as demyelinating or autoimmune disorders.
- Inform patients with IBD that these studies were both retrospective and not randomized, and are therefore subject to interpretation or selection bias.
In a second study, investigators at the University of Manitoba in Winnipeg used information from a province-wide IBD database to determine that patients with IBD were significantly more likely than matched controls to suffer from other inflammatory disease such as asthma, arthritis, bronchitis, psoriasis, and pericarditis.
In the Canadian study, patients with ulcerative colitis (but not Crohn's disease) were also significantly more likely to have chronic renal disease and MS.
The studies "underline the propensity of our patients with IBD for developing autoimmune disorders affecting multiple organ systems," wrote Edward V. Loftus, Jr., M.D., of the Mayo Clinic College of Medicine in Rochester, Minn., in an editorial accompanying the studies. All three articles are published in the September issue of Gastroenterology.
The Philadelphia group, led by James D. Lewis, M.D., of the Penn Presbyterian Medical Center, conducted a retrospective cohort study and a retrospective cross-sectional study of data on 7,988 patients with Crohn's disease and 12,185 with ulcerative colitis who were treated between 1988 and 1997.
They were prompted to look for a possible link on the basis of historical studies showing an approximate threefold risk for MS in IBD patients, and on more recent reports of MS or similar conditions in patients being treated with drugs that inhibit tumor necrosis factor-α (TNFα). These agents include the monoclonal antibodies Remicade (infliximab), Humira (adalimumab), and the fusion protein Enbrel (etanercept).
They matched the cases to 80,666 randomly selected controls from primary care practices.
The investigators found that in the cohort study the incidences of MS, demyelination, and optic neuritis were significantly higher among patients with IBD. The incidence rate ratio -- the likelihood of being diagnosed with one of the demyelination disorders after an IBD diagnosis compared with controls -- was 2.63 (95% confidence interval, 1.29-5.15), for patients with ulcerative colitis, and 2.12 (95% CI, .94-4.50) for patients with Crohn's. The IRR for optic neuritis did not reach statistical significance.
In the cross-sectional study, the odds ratio that a patient with Crohn's disease would have MS or one of the other conditions was 1.54 (95% CI, 1.03-2.32). For patients with ulcerative colitis the OR was 1.75 (95% CI, 1.28-2.39).
"Demyelinating diseases occur more frequently among patients with IBD than among non-IBD patients," the authors wrote. They added that further studies may determine whether treatment with TNFα blockers contribute to the incidence of MS and related disorders in these patients.
The Canadian study, by Charles N. Bernstein, M.D., and colleagues at the University of Manitoba in Winnipeg, used longitudinal data from 1984 to 2003 from a population-based database in the province. They selected 10 controls for every one patient with IBD, matched for age, sex, and geographic locations.
They found a total of 8,072 cases of IBD in the study period, comprising 3,879 patients with ulcerative colitis, and 4,193 with Crohn's, and looked for the rate of co-morbidities in this group and in the controls. They determined a co-morbidity to be any condition (based on ICD-9 coding) requiring five or more health-system contacts.
They found that patients with colitis were significantly more likely than controls to have asthma, bronchitis, arthritis, MS, chronic renal disease, psoriasis and pericarditis. Patients with Crohn's disease had elevated prevalence of all of these conditions as well, with the exception of chronic renal disease and MS.
"The finding of asthma as the most common co-morbidity increased in Crohn's disease is novel," Dr. Bernstein and colleagues wrote. "These may be diseases with common causes or complications of one disease that lead to the presentation with another. Studies such as this should encourage further research into the common triggers in the organ systems that lead to autoimmune diseases."
As pointed out by Dr. Loftus in his accompanying editorial, "many immune-mediated conditions are thought, like IBD, to be polygenic, and it is likely that some of these conditions share susceptibility genes, both in the major histocompatibility region of chromosome 6 and in non-major histocompatibility areas."
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