Initial therapy for mild to moderate Crohn's disease: mesalamine or budesonide?

The initial choice of therapy for mild to moderately active Crohn's disease is controversial. Both the National Cooperative Crohn's Disease Study (NCCDS) and the European Cooperative Crohn's Disease Study (ECCDS) demonstrated that sulfasalazine is effective for the induction of remission. Subsequent studies of new mesalamine formulations showed inconsistent results; two trials, however, demonstrated a statistically significant improvement with Pentasa and Asacol treatment, and meta-analyses suggest a modest benefit of mesalamine maintenance therapy. The NCCDS and ECCDS trials found that corticosteroid therapy is much more effective than sulfasalazine for induction of remission, but corticosteroids did not show maintenance benefits. Corticosteroid use is frequently associated with adverse effects, and the majority of patients treated with prednisone become either steroid-refractory or steroid-dependent; many of these patients ultimately need treatment with immunosuppressives and/or surgery. Budesonide, a topical corticosteroid with high first-pass hepatic metabolism, is slightly less effective in inducing remission than conventional corticosteroids but is significantly less likely to cause side effects. Budesonide 9 mg/day was shown to be more effective than mesalamine (Pentasa 4 g/day) for induction therapy, but budesonide has been ineffective as a maintenance therapy. Mesalamine may be useful for patients with more extensive disease, those intolerant of sulfasalazine, or those with contraindications or intolerance to budesonide. Alternatively, sulfasalazine is effective in the presence of colonic disease. Clinicians must decide on the basis of the existing evidence whether budesonide or mesalamine is the preferred initial therapy for active Crohn's disease.     

Gene therapy for lung disease: hype or hope?

Gene therapy, the treatment of any disorder or pathophysiologic state on the basis of the transfer of genetic information, was a high-priority goal in the 1990s. The lung is a major target of gene therapy for genetic disorders, such as cystic fibrosis and alpha1-antitrypsin deficiency, and for other diseases, including lung cancer, malignant mesothelioma, pulmonary inflammation, surfactant deficiency, and pulmonary hypertension. This paper examines general concepts in gene therapy, summarizes the results of published clinical trials, and highlights areas of research aimed at overcoming challenges in the field. Although progress has been slower than anticipated, gene transfer has been safely achieved in patients with lung diseases. Recent advancements in understanding of the molecular basis of lung disease and the development of improved vector systems make it likely that gene therapy will be an important tool for the 21st-century clinician.     

What options do we have for induction therapy for Crohn's disease?

The first goal of Crohn's disease treatment is to induce a response. The choice of induction therapy depends on a number of factors. First, disease severity will dictate the level of intensity of treatment. Moderate to severely active Crohn's disease needs to be treated more aggressively than mild disease. Second, it is important to consider the disease distribution, since some medications (e.g. 5-aminosalicylates, budesonide, antibiotics) are more effectively delivered to the small bowel or the colon. Third, prior medications need to be considered. A patient na?ve to immunomodulators and anti-TNF agents will be managed very differently from a patient who has already failed two anti-TNF drugs. A fourth critical factor is considering the individual patient. The balance of benefits and risks will depend upon the patient's expected disease course, and how much risk they are at personally for serious adverse events related to treatment. In addition, patients' preferences for treatment need to be addressed since they will choose therapies differently based on their personal experience with symptoms, thresholds for risk taking, and fears about their disease and treatment. The basic armamentarium for induction therapy for Crohn's disease includes: 5-aminosalicylates, antibiotics, budesonide, systemic corticosteroids, thiopurines, methotrexate, and anti-TNF agents. These drugs can be used alone or combined in difference treatment algorithms to optimize therapy. The art of treating the IBD patient is in understanding the options and being able to apply an individualized regimen based upon unique patient and disease factors.     

True or false? The hygiene hypothesis for Crohn's disease

The "hygiene hypothesis" for Crohn's disease postulates that multiple childhood exposures to enteric pathogens protect an individual from developing Crohn's disease later in life, while individuals raised in a more sanitary environment are more likely to develop Crohn's disease. In this issue of the American Journal of Gastroenterology, two Canadian case-control studies come to diametrically opposed conclusions regarding the hygiene hypothesis for Crohn's disease. This difference may be partially related to differences in study population (population based vs hospital based), age of onset, different genetic determinants, urban/rural residence (40% rural vs principally urban), or different exposures from the putative causative agent. As of now, the veracity of the hygiene hypothesis for Crohn's disease is not confirmed.     

Do patients consider postoperative maintenance therapy for Crohn's disease worthwhile?

BACKGROUND: Treatment decision making for postoperative Crohn's disease is complex because of the increasing number of maintenance therapies available with competing risk-benefit profiles. The main objective of this study was to determine the distribution of patients' preferences for selected postoperative maintenance therapies. METHODS: The study was a cross-sectional survey in which patients with Crohn's disease completed a standardized interview. Each participant completed 5 tasks that compared: (1) no medication and 5-ASA, (2) fish oil and 5-ASA, (3) metronidazole and 5-ASA, (4) budesonide and 5-ASA, and (5) azathioprine and 5-ASA. For each task, the minimum change in treatment effect size between the 2 treatments that the participant considered worthwhile was determined. RESULTS: The distribution of the participants' preference scores varied widely for each task. When fish oil, metronidazole, budesonide, and azathioprine were considered equally effective to 5-ASA, 92.9%, 28.8%, 38.4%, and 19% of the participants, respectively, preferred these medications relative to 5-ASA. These percentages increased to 98.4%, 54.8%, 61.9%, and 50.8%, respectively, when fish oil, metronidazole, budesonide, and azathioprine were considered to offer a 5% absolute risk reduction relative to 5-ASA. Regression analysis did not identify any clinical or demographic variables predictive of the participants' treatment preferences. CONCLUSIONS: The participants' preferences for postoperative maintenance therapies were widely distributed, and no clinical or demographic factors predicted these preferences. This emphasizes the need for effective communication between physician and patient in order to select the treatment options most consistent with a patient's informed preferences.