Purpose: We performed a systematic review to determine the clinical effectiveness of three anti-TNF-α agents (infliximab, adalimumab, etanercept) in patients with Crohn’s disease (CD) who have inadequate response to conventional therapy. This review further considered the evidence on the harms and benefits associated with potential immunogenicity and optimal timing of treatment with anti-TNF-α agents.
Method: An electronic literature search was conducted to identify randomized controlled trials (RCT) and observational studies on CD and anti-TNF-a drugs that were published from 1996-2008 using Medline, EMBASE, PubMed, Wiley’s Cochrane Library, and Thomson’s BIOSIS Previews. Websites of professional associations were also searched, and grey literature was identified from several sources. The assessment of study eligibility and methodological quality was performed by two independent reviewers.
Result: Of 2557 citations identified by systematic search, 13 RCTs and 6 observational studies remained in the review after applying the study inclusion and exclusion criteria. Included effectiveness trials were largely placebo-controlled, and only one study was on etanercept. Findings indicate that both infliximab and adalimumab are effective in induction and maintenance of clinical response and remission in patients with luminal CD who are resistant or refractory to conventional therapy. Induction and maintenance therapy with Infliximab were shown to significantly increase the fistula response and remission rates. A statistically significant difference between adalimumab and placebo groups was reported, in one study, only when adalimumab was used as maintenance therapy. The results of this review show that patients who maintained response to infliximab had significantly lower levels of antibodies against infliximab (ATI) than those who lost response. Patients on episodic treatment had higher incidence of antibody formation compared to patients treated with scheduled infliximab therapy. There was a negative relationship between levels of ATIs and duration of response. A negative relationship was also shown between non-response to adalimumab treatment and presence and concentration of antibodies against this drug. Treatment with both infliximab and adalimumab was shown to improve remission rates when given earlier in the disease course. Conclusion: Infliximab and adalimumab have shown a consistent superiority to placebo in induction and maintenance of clinical remission. The presence of antibodies against either drug appeared to have a negative impact on clinical effectiveness. CD patients may benefit more from anti-TNF-a therapy earlier in their disease course.
Candidate for the Lee B. Lusted Student Prize Competition