Adalimumab in Patients With Crohn's Disease - Safety and Efficacy
Adalimumab in Patients With Crohn's Disease - Safety and Efficacy
Aim: To evaluate the efficacy and safety of adalimumab, a human antitumour necrosis factor-α antibody, in induction and maintenance of remission in patients with Crohn's disease either refractory or intolerant to infliximab in a single centre cohort.
Methods: Sixteen Crohn's disease patients received 160 mg adalimumab subcutaneously in week 0, followed by 80 mg every other week. Clinical response was assessed based on Crohn's disease activity index and laboratory parameters (leukocyte count, C-reactive protein). In all patients genotyping for CARD15 variants and the +1059G/C polymorphism in the C-reactive protein gene was performed.
Results: In 10 of 16 patients (63%) treated with adalimumab, remission (CDAI score <150) was induced for at least 8 weeks independent of CARD15 or +1059G/C CRP status. In six of these 10 patients ongoing remission is observed now for more than 24 weeks. Adalimumab significantly decreased C-reactive protein serum levels and Crohn's disease activity index. There was one serious complication (fungal pneumonia). Six patients intermittently developed minor dermatological problems resolving after topical therapy. Otherwise, treatment was generally well tolerated.
Conclusion: Adalimumab can induce and maintain remission in patients with moderate to severe Crohn's disease intolerant or refractory to infliximab. Further experience from larger cohorts is required to evaluate dose regimen and safety profiles in Crohn's disease therapy.
Tumour necrosis factor-alpha (TNF-α) plays a pivotal role in the pathogenesis of mucosal inflammation in inflammatory bowel disease (IBD). Therefore, anti-TNF-α therapy is used as effective anti-inflammatory and disease-modifying treatment strategy in IBD. Infliximab (Remicade, Centocor Inc., Malvern, PA, USA) was the first chimaeric monoclonal TNF-α antibody used in clinical practice for IBD. It has shown to be effective in induction and maintenance of remission in patients with active and fistulizing Crohn's disease (CD) and in patients with severe ulcerative colitis (UC). Infliximab is composed of 75% human and 25% murine sequences with potential immunogenicity caused by human antichimaeric antibodies (HACA). This may result in loss of efficacy, hypersensitivity reactions or infusion reactions.
Adalimumab (Humira, D2E7; Abbott Laboratories, Chicago, IL, USA) is a recombinant fully human IgG1 antibody targeting human TNF-α with high affinity and specificity. It might therefore be a therapeutic option for IBD patients intolerant or refractory to infliximab. So far, adalimumab has shown positive clinical effects in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. In addition, a limited number of studies in CD patients demonstrated promising results in both, patients intolerant or nave to anti-TNF therapy. Overall, adalimumab was well tolerated in these initial studies. However, given the so far limited clinical experience in CD and potential safety risks associated with effective TNF-α-blockade, further studies evaluating adalimumab for induction and maintenance of remission in severe CD are required before general conclusions can be drawn. In addition, the majority of the studies investigating adalimumab so far are pharmaceutical industry-sponsored multicentre trials which combined small single centre patient cohorts resulting in heterogeneous patient groups. Here, we present our clinical experience with adalimumab in a single centre cohort study - funded independent of the pharmaceutical industry - in a cohort of patients with moderate to severe CD either refractory or intolerant to infliximab.
Summary and Introduction
Summary
Aim: To evaluate the efficacy and safety of adalimumab, a human antitumour necrosis factor-α antibody, in induction and maintenance of remission in patients with Crohn's disease either refractory or intolerant to infliximab in a single centre cohort.
Methods: Sixteen Crohn's disease patients received 160 mg adalimumab subcutaneously in week 0, followed by 80 mg every other week. Clinical response was assessed based on Crohn's disease activity index and laboratory parameters (leukocyte count, C-reactive protein). In all patients genotyping for CARD15 variants and the +1059G/C polymorphism in the C-reactive protein gene was performed.
Results: In 10 of 16 patients (63%) treated with adalimumab, remission (CDAI score <150) was induced for at least 8 weeks independent of CARD15 or +1059G/C CRP status. In six of these 10 patients ongoing remission is observed now for more than 24 weeks. Adalimumab significantly decreased C-reactive protein serum levels and Crohn's disease activity index. There was one serious complication (fungal pneumonia). Six patients intermittently developed minor dermatological problems resolving after topical therapy. Otherwise, treatment was generally well tolerated.
Conclusion: Adalimumab can induce and maintain remission in patients with moderate to severe Crohn's disease intolerant or refractory to infliximab. Further experience from larger cohorts is required to evaluate dose regimen and safety profiles in Crohn's disease therapy.
Introduction
Tumour necrosis factor-alpha (TNF-α) plays a pivotal role in the pathogenesis of mucosal inflammation in inflammatory bowel disease (IBD). Therefore, anti-TNF-α therapy is used as effective anti-inflammatory and disease-modifying treatment strategy in IBD. Infliximab (Remicade, Centocor Inc., Malvern, PA, USA) was the first chimaeric monoclonal TNF-α antibody used in clinical practice for IBD. It has shown to be effective in induction and maintenance of remission in patients with active and fistulizing Crohn's disease (CD) and in patients with severe ulcerative colitis (UC). Infliximab is composed of 75% human and 25% murine sequences with potential immunogenicity caused by human antichimaeric antibodies (HACA). This may result in loss of efficacy, hypersensitivity reactions or infusion reactions.
Adalimumab (Humira, D2E7; Abbott Laboratories, Chicago, IL, USA) is a recombinant fully human IgG1 antibody targeting human TNF-α with high affinity and specificity. It might therefore be a therapeutic option for IBD patients intolerant or refractory to infliximab. So far, adalimumab has shown positive clinical effects in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. In addition, a limited number of studies in CD patients demonstrated promising results in both, patients intolerant or nave to anti-TNF therapy. Overall, adalimumab was well tolerated in these initial studies. However, given the so far limited clinical experience in CD and potential safety risks associated with effective TNF-α-blockade, further studies evaluating adalimumab for induction and maintenance of remission in severe CD are required before general conclusions can be drawn. In addition, the majority of the studies investigating adalimumab so far are pharmaceutical industry-sponsored multicentre trials which combined small single centre patient cohorts resulting in heterogeneous patient groups. Here, we present our clinical experience with adalimumab in a single centre cohort study - funded independent of the pharmaceutical industry - in a cohort of patients with moderate to severe CD either refractory or intolerant to infliximab.
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