Adalimumab Maintenance Therapy for Crohn's Disease
Adalimumab Maintenance Therapy for Crohn's Disease
Background: Adalimumab is effective in inducing remission in patients with active Crohn's disease who had secondary failure to infliximab therapy.
Aim: To evaluate the efficacy and safety of adalimumab maintenance therapy in Crohn's disease patients who previously responded to infliximab and then lost response or became intolerant.
Methods: Twenty-four patients with Crohn's disease were enrolled in a 52-week open-label trial. The patients received a loading dose of adalimumab 80-mg at week 0, and then 40 mg every other week starting at week 2. The primary efficacy measure was clinical remission defined as Crohn's Disease Activity Index score < 150 at week 52.
Results: Five patients lost response to adalimumab. None of the patients experienced intolerance to adalimumab. Clinical remission rates were higher at weeks 4 (16/24, 67%) and 52 (14/24, 58%) compared with baseline (8/24, 35%) (P= 0.043 at week 52). This was accompanied by a decrease in mean C-reactive protein concentration from 31.8 mg/mL at baseline to 9.7 mg/mL at week 52, and 3/4 (75%) patients achieved steroid-free remission. No serious toxicities occurred in the study.
Conclusions: Adalimumab is well tolerated and appears to be effective in maintaining clinical remission in patients with Crohn's disease and lost response or intolerance to infliximab.
Tumour necrosis factor (TNF) is a cytokine playing a key role in the pathogenesis of Crohn's disease (CD). Infliximab, a chimeric monoclonal antibody to TNF, is effective in inducing and maintaining response and remission in patients with moderate to severe CD. However, infliximab is immunogenic and repeated administration can result in the development of antibodies to infliximab that lead to infusion reactions, loss of efficacy and delayed hypersensitivity reactions.
Two anti-TNF agents which might be less immunogenic, namely adalimumab and certolizumab (a PEGylated humanized Fab' fragment to TNF), have proven efficacy in the treatment of CD refractory to standard medical therapy with corticosteroids or immunomodulatory agents. Adalimumab is a recombinant human IgG1 human monoclonal antibody that binds with high affinity and specificity to human soluble TNF but not to lymphotoxin. In three placebo-controlled trials, adalimumab was effective for both induction and maintenance of clinical response and remission in moderate to severe CD.
Recently, two uncontrolled trials and a 4-week randomized placebo-controlled trial named Gauging Adalimumab Efficacy in Infliximab Non-responders (GAIN) have demonstrated that adalimumab therapy was also effective in inducing remission in patients with active CD who had previously responded to infliximab and then lost response or became intolerant. Preliminary data from a retrospective study suggested that adalimumab may be an effective maintenance therapy for patients with CD who have experienced an attenuated response to infliximab. However, the long-term efficacy of adalimumab beyond 6 months in these patients is unknown.
We conducted a 52-week open-label trial to assess the long-term efficacy and safety of subcutaneous administration of adalimumab in CD patients who had an attenuated response to infliximab or had become intolerant to infliximab therapy.
Summary and Introduction
Summary
Background: Adalimumab is effective in inducing remission in patients with active Crohn's disease who had secondary failure to infliximab therapy.
Aim: To evaluate the efficacy and safety of adalimumab maintenance therapy in Crohn's disease patients who previously responded to infliximab and then lost response or became intolerant.
Methods: Twenty-four patients with Crohn's disease were enrolled in a 52-week open-label trial. The patients received a loading dose of adalimumab 80-mg at week 0, and then 40 mg every other week starting at week 2. The primary efficacy measure was clinical remission defined as Crohn's Disease Activity Index score < 150 at week 52.
Results: Five patients lost response to adalimumab. None of the patients experienced intolerance to adalimumab. Clinical remission rates were higher at weeks 4 (16/24, 67%) and 52 (14/24, 58%) compared with baseline (8/24, 35%) (P= 0.043 at week 52). This was accompanied by a decrease in mean C-reactive protein concentration from 31.8 mg/mL at baseline to 9.7 mg/mL at week 52, and 3/4 (75%) patients achieved steroid-free remission. No serious toxicities occurred in the study.
Conclusions: Adalimumab is well tolerated and appears to be effective in maintaining clinical remission in patients with Crohn's disease and lost response or intolerance to infliximab.
Introduction
Tumour necrosis factor (TNF) is a cytokine playing a key role in the pathogenesis of Crohn's disease (CD). Infliximab, a chimeric monoclonal antibody to TNF, is effective in inducing and maintaining response and remission in patients with moderate to severe CD. However, infliximab is immunogenic and repeated administration can result in the development of antibodies to infliximab that lead to infusion reactions, loss of efficacy and delayed hypersensitivity reactions.
Two anti-TNF agents which might be less immunogenic, namely adalimumab and certolizumab (a PEGylated humanized Fab' fragment to TNF), have proven efficacy in the treatment of CD refractory to standard medical therapy with corticosteroids or immunomodulatory agents. Adalimumab is a recombinant human IgG1 human monoclonal antibody that binds with high affinity and specificity to human soluble TNF but not to lymphotoxin. In three placebo-controlled trials, adalimumab was effective for both induction and maintenance of clinical response and remission in moderate to severe CD.
Recently, two uncontrolled trials and a 4-week randomized placebo-controlled trial named Gauging Adalimumab Efficacy in Infliximab Non-responders (GAIN) have demonstrated that adalimumab therapy was also effective in inducing remission in patients with active CD who had previously responded to infliximab and then lost response or became intolerant. Preliminary data from a retrospective study suggested that adalimumab may be an effective maintenance therapy for patients with CD who have experienced an attenuated response to infliximab. However, the long-term efficacy of adalimumab beyond 6 months in these patients is unknown.
We conducted a 52-week open-label trial to assess the long-term efficacy and safety of subcutaneous administration of adalimumab in CD patients who had an attenuated response to infliximab or had become intolerant to infliximab therapy.
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