[Adalimumab for the Treatment of Adult Crohn's Disease - Update of a Consensus Report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology.]
ABSTRACT TNF alpha antibodies have clearly improved the outcome of moderate to severe Crohn's disease. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which can be self-administered subcutaneously. Since August 2012 adalimumab is approved for the treatment of moderately to severely active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Compared to placebo adalimumab can induce significantly more often steroid-free remission and mucosal healing in patients with moderate to severe Crohn's disease, reduce the rate of Crohn's disease-related hospitalisations and surgery and improve health-related quality of life. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to TNF-alpha antibodies and in those previously exposed with a rapid onset of action within days and confirmed maintenance performance over 3 years. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to its low immunogenicity allergic reactions are rare. The update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence on adalimumab for the treatment of Crohn's disease and is aimed to assist as a code of practice in its applications.
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ABSTRACT: Background and aims: Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30–40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients. Methods: All consecutive patients treated with open label adalimumab for active Crohn's disease from the participating centres were included in this cohort study. A detailed retrospective chart review was performed to look for possible factors predicting outcome. Results: Eighty four percent of 720 patients had a primary response and were followed up for a median of 14 months. Thirty four percent needed escalation after a median of 7 months (0–55 months). Multivariate predictors for dose escalation were the following: prior anti-TNF use (p < 0.0001), no concomitant azathioprine or < 3 m (p < 0.02) and abnormal CRP at start (p < 0.05). Dose escalation re-induced response for at least 6 months in 67%. Only abnormal CRP at start correlated with failure of dose escalation (p = 0.02). Dose de-escalation was attempted in 54% and was successful in 63%. After a median follow-up of 14 m adalimumab was discontinued in 29% of patients. Conclusion: In this study real life nationwide cohort of Crohn's patients treated with adalimumab dose escalation was needed in 34% and was successful in 67%. Dose de-escalation was attempted in 54% and was successful in 63%. Overall 71% of patients maintained long term response on adalimumab.Journal of Crohn s and Colitis 04/2012; 7(2). DOI:10.1016/j.crohns.2012.03.018 · 3.56 Impact Factor
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ABSTRACT: Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population. This analysis included 19,041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and juvenile idiopathic arthritis (JIA) to 15 April 2007. Events per 100 patient-years were calculated using SAE reported after the first dose to 70 days after the last dose. Standardised incidence rates were calculated for malignancies using national and state-specific databases. Standardised mortality rates (SMR) were calculated for each disease using data from the World Health Organization. Cumulative rates of SAE of interest in RA have remained stable over time. Rates of SAE of interest for PsA, AS, CD, psoriasis and JIA were similar to or lower than rates for RA. Overall malignancy rates for adalimumab-treated patients were as expected for the general population. SMR across all six diseases indicated that no more deaths occurred with adalimumab than expected in the general population. Based on 10 years of clinical trial experience across six diseases, this safety report and the established efficacy of adalimumab in these diseases provide the foundation for a better understanding of its benefit-risk profile.Annals of the rheumatic diseases 02/2009; 68(12):1863-9. DOI:10.1136/ard.2008.102103 · 10.38 Impact Factor
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ABSTRACT: Background As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited. Objective To analyse the long-term safety of adalimumab treatment. Methods This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data. Results The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population. Conclusions Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.Annals of the rheumatic diseases 05/2012; 72(4). DOI:10.1136/annrheumdis-2011-201244 · 10.38 Impact Factor