RESUMO
The effectiveness of ant-TNF 'biologic' therapy in is well supported in the management of moderate to severe Crohn's Disease (CD). Our first 'SAVANT' study was to our knowledge the first study report one- year outcomes in patients (n=60) who switched from previous anti-TNFa treatment to Cimzia/Certolizumab. This current study (SAVANT 2) follows up on longer term outcomes and provides additional clinical and biochemical data that may contribute to therapeutic responses. This IRB approved study was a retrospective analysis of the initial patients included in SAVANT 1. Patients who were switched to TNF antagonist Certolizumab as an alternative biologic were followed an additional year. Retrospective consideration of immunomodulator use, smoking status and clinical data were also evaluated. Of 60 patients with moderate-severe CD who participated in the SAVANT 1 study, 15 patients were excluded due to inadequate follow up. 45 patients were studied for a total of two years following substitution with Certolizumab from prior anti TNF agent therapy. Clinical remission at 1 year was 75% (45/60) and 55% (25/45) at the second year. At the second year, 5 more patients had discontinued Certolizumab due to worse disease or adverse events, indicating a cumulative two-year failure rate of 33% (20/60). Smoking and concomitant use of immunomodulators were similar between 'success' and 'failure' groups. SAVANT 2, the first study to report long term outcomes of switching from Infliximab or Adalimumab to Certolizumab showed that at 2 years, 25 patient's maintained clinical remission. The discontinuation rates were 25 and 11% at years 1 & 2 respectively. The 5 patients who lost responsiveness after the first year were women, the majority of smoked. Additional prospective studies to assess the appropriateness and feasibility of biologic substitution are still needed.
RESUMO
BACKGROUND: Biological therapy targeting tumor necrosis factor-alfa has revolutionized the treatment of Crohn's disease (CD). Our study retrospectively reviewed clinical outcomes of 60 patients administratively substituted from Infliximab or Adalimumab to Certolizumab. Maintenance of disease and failure rates after substitution of anti-tumor necrosis factor-alfa agents in CD patients were monitored over 1 year, and this is the first outcomes study of patients maintained on Infliximab or Adalimumab substituted to Certolizumab. METHODS: A hospital pharmacy directive required all patients on biological therapy to be administratively substituted to Certolizumab therapy. This single-center retrospective analysis initially included 68 CD patients presenting at Louisiana State University Health Sciences Center-Shreveport. Clinical, endoscopic, and serologic data were compared at baseline and at 4 intervals over 1 year. RESULTS: Of 60 enrolled CD patients, 45 (75%) successfully transitioned to Certolizumab and had stable disease at 1 year. Of the 15 (25%) patients who "failed" substitution at 1 year, 5 were returned to Adalimumab and 7 to Infliximab; 3 were maintained on steroids awaiting subsequent therapy. Importantly, when patients were segregated on the basis of initial disease control, it was found that 3 (12.5%) previously well-controlled patients failed therapy, whereas 12 (33.3%) who initially had active disease failed Certolizumab substitution. CONCLUSIONS: Our study found that 25% of CD patients substituted to Cimzia failed substitution, whereas 75% still exhibited a good clinical response with stable disease at 1 year. Our findings indicate that disease status and behavior at the time of biological substitution may predict therapeutic responsiveness.