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QUESTION: In patients with Crohn’s disease, what is the natural history of the disease?
Studies were identified by searching Medline, Current Contents (1966 to September 2000), and bibliographies of relevant studies.
2 reviewers independently selected fully published English language trials that were population-based studies of patients followed from the time of initial diagnosis; used appropriate and objective criteria for disease; had sufficiently long and complete follow up; and quantified disease activity, medication use, and surgery.
2 reviewers independently and blindly extracted data on disease severity or activity, use of medication, and surgical resection rates. Disagreements were resolved by consensus.
3 studies of 1 population-based cohort (225 people followed from 1940–93) met the selection criteria for natural history studies. 1 study showed that a representative patient spent 24% of the lifetime disease course in medical remission, 27% with mild disease, 1% with severe drug-responsive disease, 4% with severe drug-dependent disease, 2% with severe drug-refractory disease, 1% in surgery, and 41% in postsurgical remission. Few patients had prolonged remission: 10% of patients were cured, 73% had a chronic intermittent disease course, and 13% had an unremitting disease course. Data were insufficient to determine which prognostic factors predicted prolonged remission. 43% of patients received treatment with conventional corticosteroids at some time in the disease course. In any given year, approximately 10% of patients were treated with conventional corticosteroids or other immune-modifier agents, and approximately 30% of patients were treated with 5-aminosalicyclate agents. 41% of patients had ≥1 resection, and 57% had ≥1 operative procedure.
In patients with Crohn’s disease, one tenth of patients have prolonged remission. Almost three quarters of patients have a chronic intermittent disease course, and about one eighth have an unremitting disease course. Less than one half of patients receive corticosteroids, and more than one half have at least 1 operative procedure.
The review by Loftus et al summarises data from 3 previously published studies that describe the natural history of Crohn’s disease in Olmsted County, Minnesota, USA. Since only 2 well characterised, population based, cohort studies have been done (Copenhagen 1 and Olmsted counties), this report provides valuable prognostic information. From a clinical perspective, the most important message is that most patients with Crohn’s disease have a relatively benign clinical course. At any given time, most patients are in remission; moreover, less than half of the patients in this cohort required corticosteroid treatment during their lifetime experience with the disease. Accordingly, physicians who manage these patients should be aware that much of the literature describing the prognosis of Crohn disease has originated from tertiary care centres and thus overstates the disease severity. Certainly this is reassuring news for most patients.
However, Loftus et al also note that a few patients have aggressive disease. Moreover, most patients require surgery at some time. Although disease recurrence after surgery is usually inevitable, surgically induced remission is more durable than medically induced remission, and most patients enjoy good quality of life following an operation. Thus, surgery plays an important part in overall management. This review also underscores the point that the greatest challenge for medical treatment is to modify the clinical course of patients with aggressive disease. Since it would be a great advantage to identify this subgroup on the basis of clinical characteristics, the authors’ unsuccessful search for prognostic markers is disappointing. The only characteristic that seems to predict poor prognosis is the initiation of corticosteroid treatment. On the basis of this observation, most opinion leaders now advocate the use of immunosuppressives for patients in whom a course of induction therapy with corticosteroids has failed. This strategy was relatively uncommon in Olmsted County during this period of observation; thus, further updates of these data should provide insight into whether more aggressive treatment will modify the natural history of the disease.
Source of funding: AstraZeneca LP.
For correspondence: Dr E V Loftus, Jr, Mayo Clinic, Rochester, MN, USA. E-mail.