Crohn's and Biologics--- At What Point Should They Be Used?
For years, the treatment of Crohn's disease has been based on a "step-up" approach in which therapies with the least toxicity are used early, and subsequent therapies are then added due to lack of response or toxicity. Unfortunately, agents with low efficacy such as the aminosalicylates, Asacol and Pentasa, are used for prolonged periods of time while uncontrolled inflammation results in tissue damage. Patients who fail to respond to aminosalicylates are then treated with corticosteroids in the form of prednisone. Immunosuppressant therapy is reserved for those patients with steroid-refractory or steroid-dependent disease. Many patients may stay on therapies to which they are not responding for a prolonged duration because clinicians may be reluctant to step-up to therapy that is perceived as more dangerous. Unfortunately, under this current treatment paradigm, rates of surgical intervention remain high, with as many as one third of patients requiring surgery within a year of beginning oral steroids and with no significant decrease in the need for surgery over the last several decades despite the earlier and increasing use of immunomodulators.
A recent report out of London published in Lancet postulated that earlier use of biologics to treat Crohn's disease is a better approach then using steroids first. Researchers looked at 133 patients at 18 centers in Germany, Belgium and the Netherlands. Half of the patients received the biologic Remicade, while the other half first received steroids and then the Remicade. At 26 weeks, 60% of patients treated with Remicade first were in remission, compared to 36% of the patients that had received steroids prior to Remicade.
While this data is promising, larger studies need to be performed before changes in the treatment algorithm from a "step-up" to the "top-down" approach can be recommended.
The goal of "top-down" therapy is to avoid steroids and their potential complications, achieve mucosal healing, and alter the natural history of the disease. Some people feel that by giving patients with Crohn's disease steroid therapy, one may be propagating an abnormal loss of tolerance, thereby resulting in repeated episodes of inflammation and tissue damage, particularly as the dose of steroids is tapered. The hope is that aggressive treatment of Crohn's disease, through the use of biologic therapy, will enhance treatment response, reduce the need for steroids, and perhaps change the natural history of the disease.
When we look at the differences in the ""step-up or "top-down" approaches, in addition to the" top-down" approach having a benefit of avoiding steroids, it is felt that the early introduction of biologic therapy has benefits at the end-organ level that may be even more important than just avoiding steroids. This benefit of the early use of biologic therapy has been demonstrated in rheumatoid arthritis, where the early introduction of biologic therapy results in less joint damage on x-ray as compared with a typical therapeutic approach using anti-inflammatories and steroids.