Azatioprina no tratamento de pacientes com colite ulcerativa córtico-dependente: resultados e fatores preditivos de resposta

Abstract

Ulcerative colitis (UC) is a lifelong, immune-mediated inflammatory condition of the colonic mucosa, which is characterized by a relapsing and remitting course. Corticosteroids remain one of the most effective therapies for inducing remission in patients with moderate-to-severe UC. Nonetheless, corticosteroids are not used in maintenance therapy, mainly because undesirable side effects outweigh the possible benefits. Furthermore, at one year, less than half of UC patients who require steroids have a sustained response, nearly one-third of patients require colectomy, and approximately a quarter is unable to support its withdrawal without relapsing. Thus, corticosteroid dependence in patients with UC is a pivotal clinical problem and maintenance of steroid-free remission is an important current evolving treatment goal. Patients with steroid dependent UC are usually given a choice between colectomy or stepped-up medical treatment, which traditionally involves prescription of an immunosuppressive drug. Thiopurine therapy has found widespread use for this setting in clinical practice. However, studies assessing the efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (UC) are scarce. The purpose of this trial was to explore the efficacy of AZA in maintaining steroid-free remission in steroid-dependent UC patients as well as the factors associated to sustained response. In this observational cohort study adult subjects with steroid-dependent UC were recruited for AZA therapy during a 12 months period. AZA was adjusted for a target dose of 2-3 mg/Kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the rate of patients with sustained steroid-free response to AZA at the end of 12 months. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment. A total of 42 patients were included. On an intention-to-treat basis, the proportion of patients remaining in sustained steroid-free remission at 12 months was 0.55. A significant decrease in the flare-ups rate as well as in requirement for steroids were observed during 12 months while on AZA compared with the previous year (P=0.000). Only disease duration of <36 months before the initiation of AZA was associated to off-steroids remission (P=0.02, OR 3.12 (95% CI 1.89-7.64)). AZA was well tolerated and its benefit-risk profile favorable. AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 12 months of therapy in patients with steroid dependent UC. Patients with earlier UC are those who most probably will have sustained steroid-free remission while on AZA.