A guide to prepare patients with inflammatory bowel diseases for anti-TNF-α therapy.

Current therapy of moderate-to-severe inflammatory bowel disease (IBD) often involves the use of anti-tumor necrosis factor alpha (TNF-α) agents. Although very effective, theses biologics place the patient at increased risk for developing infections and lymphomas, the latter especially when in combination with thiopurines. Appropriate patient selection, counseling, and education are all important features for the successful use of anti-TNF-α therapy. A thorough history to rule-out contraindications of this therapy and emphasis on monitoring guidelines are important steps preceding administration of anti-TNF-α agents. This therapy should only be considered if a recent evaluation has established that the patient has active IBD. In addition, it is important to exclude disease mimickers. Anti-TNF-α agents have been considered to present a globally favorable benefit/risk ratio. However, it is important that in routine practice, initiation of anti-TNF-α therapy be carefully discussed with the patient, extensively explaining the potential benefits and risks of such treatment. Prior to starting anti-TNF-α therapy, the patients need to be screened for latent tuberculosis, hepatitis B virus infection, and (usually) hepatitis C virus and HIV infection. Vaccination schedules of IBD patients should be evaluated and updated prior to the commencement of anti-TNF-α therapy. Ordinarily, immunization in adult patients with IBD should not deviate from recommended guidelines for the general population. With the exception of live vaccines, immunizations can be safely administered in patients with IBD, even those on immunosuppressants or biologics. The purpose of this review is providing an overview of appropriate steps to prepare patients with IBD for anti-TNF-α therapy.

Azathioprine therapy in steroid-dependent patients with Crohn disease: results of a 10-year longitudinal follow-up study.

BACKGROUND: Studies assessing the efficacy of azathioprine in steroid-dependent patients with Crohn's disease are scarce. The aim of this study was to assess the long-term efficacy and safety of azathioprine, and factors associated with sustained response, in steroid-dependent patients with Crohn's disease. MATERIAL/METHODS: In this prospective, observational study, adult steroid-dependent subjects with Crohn's disease receiving azathioprine therapy were assessed over a 10-year period. Azathioprine dosage was adjusted according to clinical response and occurrence of adverse events. Median treatment duration was 83 months. Steroid therapy was tapered according to protocol. RESULTS: A total of 106 subjects were included. The proportion of subjects remaining in sustained steroid-free remission at 12, 24, 36, 48, and 60 months was 0.61, 0.73, 0.72, 0.70, and 0.70, respectively. Thereafter, the rate of weaning from steroids decreased gradually, reaching a nadir of 0.41 at 108 months. Median time to complete steroid withdrawal was 6 months. Demographic, azathioprine dose, and disease-related data did not correlate with remission. By multivariate analysis, only decreased mean leukocyte count during follow-up was independently associated with steroid-free remission (P=.001). Subjects who achieved an annual mean leukocyte count <6,000/mm(3) were more likely to sustain steroid-free remission (P=.01). Serious adverse events in response to azathioprine were uncommon. CONCLUSIONS: Azathioprine therapy offers a meaningful option in the management of steroid-dependent Crohn's disease for up to 10 years. A persistent decrease in leukocyte count may provide a surrogate marker of sustained steroid-free response.

Long-term results with azathioprine therapy in patients with corticosteroid-dependent Crohn's disease: open-label prospective study.

BACKGROUND: A substantial number of patients with Crohn's disease (CD) become dependent on steroids after induction therapy. Treatment with azathioprine (AZA) may be beneficial in such patients. The present open-label study evaluated the long-term safety and efficacy of AZA in steroid-dependent CD patients. METHODS: Adult patients with steroid-dependent CD were enrolled for AZA therapy over a 7-year period. The average dose of AZA was 2.0-3.0 mg/kg per day, adjusted according to clinical response and occurrence of adverse effects. Steroid therapy was tapered off according to a predefined schedule. Long-term outcome and adverse reactions were evaluated. RESULTS: Sixty-nine patients were prospectively included. Steroid-free remission was achieved in 68-81% of patients, partial response in 14.5-27.3% and failure to respond to AZA in 4-15.9% over the initial 48 months. However, the rate of wean from steroid therapy decreased to 53-60% while the rate of failure increased from 6.7% to 17.6% after this period. A breakthrough of symptoms during continuous AZA therapy was common, particularly after 48 months on AZA. The mean leukocyte count at the end of 12 months of therapy was significantly lower in patients who achieved complete response on AZA than in the non-responders (5197 +/- 1250 cells/mm(3) vs 8340 +/- 1310 cells/mm(3), respectively; P < 0.01). Azathioprine was relatively well-tolerated and the incidence of serious adverse effects was small. CONCLUSIONS: Azathioprine was relatively safe and moderately effective for long-term maintenance of steroid-free clinical remission in corticosteroid-dependent CD patients. Patients were more successfully weaned from prednisone treatment, and clinical remission was more often maintained during the first 48 months of AZA therapy. A significant decrease in the white blood cell count at the end of 12 months on AZA was the single factor associated with weaning from steroid dependence.