Efficacy and Safety of Infliximab and Adalimumab in CD
Efficacy and Safety of Infliximab and Adalimumab in CD
Background Infliximab and adalimumab are highly effective in Crohn's Disease (CD). This is supported by clinical trials and open-label studies using either infliximab or adalimumab, thus not allowing a proper comparison between these anti-TNFs in CD.
Aim To evaluate the efficacy and safety of infliximab and adalimumab in active CD.
Methods In a longitudinal study, CD patients with indication for anti-TNFs were treated with infliximab or adalimumab.
Results Ninety-three patients were treated with infliximab (n = 44) or adalimumab (n = 49). In the infliximab group, the induction was completed by 77.3% of patients, due to no response (n = 2), delayed hypersensitivity reactions (DHR) or infusion reactions (n = 8). Maintenance with infliximab was completed by 60% of patients, due to clinical worsening or loss of efficacy (n = 5), DHR or infusion reactions (n = 5). In the adalimumab group, all patients completed the induction, while maintenance was completed by 67% of patients, due to clinical worsening or loss of efficacy (n = 8), DHR (n = 1), other causes (n = 7). In both groups, the CDAI significantly reduced at baseline vs. each visit (P < 0.04). The Kaplan–Meier survival analysis performed to evaluate the risk of steroid-free remission in patients treated with infliximab vs. adalimumab detected no differences (log-rank test P = 0.4). Cox proportional-hazards regression identified two predictors of steroid-free remission using anti-TNFs: no smokers [HR = 2.94 (1.52–5.70), P = 0.001] and non stricturing non penetrating behaviour [HR = 3.116 (1.06–9.13), P = 0.03826].
Conclusions Infliximab and adalimumab showed a similar efficacy. No smoking and non-stricturing non-penetrating behaviour were predictors of steroid-free remission.
Crohn's disease (CD) is a chronic IBD of unknown aetiology. A dysregulation of the mucosal immune response appears to be involved in the pathogenesis of tissue damage. Experimental evidences concordantly support a key role of tumour necrosis factor alpha (TNF-α) in the induction and perpetuation of the inflammatory process in CD tissue. On the basis of these observations, a chimerical monoclonal antibody specifically targeting TNF-α has been developed, showing a dramatic efficacy in CD. Since then, infliximab has been widely used in CD, including patients refractory to conventional treatments. Mucosal healing has also been reported in subgroups of responsive patients. Limits of infliximab are mainly represented by possible incomplete response, loss of response and/or side effects. These unfavourable outcomes may be related to the murine component of the drug and to the possible development of antibodies against infliximab, which may be associated with infusion reactions (6.9–19%). Due to the proven efficacy of this anti-TNF, other molecules providing the same immunomodulatory effect have been developed. Adalimumab, a fully humanised anti-TNF monoclonal antibody showed a proven efficacy for inducting and maintaining remission in CD. As for infliximab, mucosal healing has been described in preliminary reports after 1 year treatment with adalimumab. Adalimumab therefore appears to represent an additional effective anti-TNF treatment in CD. Switching anti-TNF treatments is also indicated in patients showing loss of response or side effects when using one of the two anti-TNFs. Adalimumab may be effective and well tolerated also in CD patients refractory or intolerant to infliximab. The humanised adalimumab also induces a lower frequency of side effects related to the murine component of infliximab, although no comparative studies using these anti-TNFs are available. All these observations indeed derive from comparisons between clinical trials including different study populations and study designs, thus not allowing a proper comparison between these highly effective drugs in CD. To our knowledge, no observations reported in the same study the safety and efficacy of infliximab and adalimumab in patients with CD. Primary end point of this study was to investigate, in a consecutive series of CD patients, the efficacy of infliximab and adalimumab, as evaluated by the assessment of clinical activity, steroids-free remission and quality of life. Secondary end point included the assessment of the safety profile of infliximab and adalimumab.
Abstract and Introduction
Abstract
Background Infliximab and adalimumab are highly effective in Crohn's Disease (CD). This is supported by clinical trials and open-label studies using either infliximab or adalimumab, thus not allowing a proper comparison between these anti-TNFs in CD.
Aim To evaluate the efficacy and safety of infliximab and adalimumab in active CD.
Methods In a longitudinal study, CD patients with indication for anti-TNFs were treated with infliximab or adalimumab.
Results Ninety-three patients were treated with infliximab (n = 44) or adalimumab (n = 49). In the infliximab group, the induction was completed by 77.3% of patients, due to no response (n = 2), delayed hypersensitivity reactions (DHR) or infusion reactions (n = 8). Maintenance with infliximab was completed by 60% of patients, due to clinical worsening or loss of efficacy (n = 5), DHR or infusion reactions (n = 5). In the adalimumab group, all patients completed the induction, while maintenance was completed by 67% of patients, due to clinical worsening or loss of efficacy (n = 8), DHR (n = 1), other causes (n = 7). In both groups, the CDAI significantly reduced at baseline vs. each visit (P < 0.04). The Kaplan–Meier survival analysis performed to evaluate the risk of steroid-free remission in patients treated with infliximab vs. adalimumab detected no differences (log-rank test P = 0.4). Cox proportional-hazards regression identified two predictors of steroid-free remission using anti-TNFs: no smokers [HR = 2.94 (1.52–5.70), P = 0.001] and non stricturing non penetrating behaviour [HR = 3.116 (1.06–9.13), P = 0.03826].
Conclusions Infliximab and adalimumab showed a similar efficacy. No smoking and non-stricturing non-penetrating behaviour were predictors of steroid-free remission.
Introduction
Crohn's disease (CD) is a chronic IBD of unknown aetiology. A dysregulation of the mucosal immune response appears to be involved in the pathogenesis of tissue damage. Experimental evidences concordantly support a key role of tumour necrosis factor alpha (TNF-α) in the induction and perpetuation of the inflammatory process in CD tissue. On the basis of these observations, a chimerical monoclonal antibody specifically targeting TNF-α has been developed, showing a dramatic efficacy in CD. Since then, infliximab has been widely used in CD, including patients refractory to conventional treatments. Mucosal healing has also been reported in subgroups of responsive patients. Limits of infliximab are mainly represented by possible incomplete response, loss of response and/or side effects. These unfavourable outcomes may be related to the murine component of the drug and to the possible development of antibodies against infliximab, which may be associated with infusion reactions (6.9–19%). Due to the proven efficacy of this anti-TNF, other molecules providing the same immunomodulatory effect have been developed. Adalimumab, a fully humanised anti-TNF monoclonal antibody showed a proven efficacy for inducting and maintaining remission in CD. As for infliximab, mucosal healing has been described in preliminary reports after 1 year treatment with adalimumab. Adalimumab therefore appears to represent an additional effective anti-TNF treatment in CD. Switching anti-TNF treatments is also indicated in patients showing loss of response or side effects when using one of the two anti-TNFs. Adalimumab may be effective and well tolerated also in CD patients refractory or intolerant to infliximab. The humanised adalimumab also induces a lower frequency of side effects related to the murine component of infliximab, although no comparative studies using these anti-TNFs are available. All these observations indeed derive from comparisons between clinical trials including different study populations and study designs, thus not allowing a proper comparison between these highly effective drugs in CD. To our knowledge, no observations reported in the same study the safety and efficacy of infliximab and adalimumab in patients with CD. Primary end point of this study was to investigate, in a consecutive series of CD patients, the efficacy of infliximab and adalimumab, as evaluated by the assessment of clinical activity, steroids-free remission and quality of life. Secondary end point included the assessment of the safety profile of infliximab and adalimumab.