Efficacy and Safety of Tumor Necrosis Factor Antagonists in Crohn’s Disease: Meta-Analysis of Placebo-Controlled Trials

Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association (Impact Factor: 7.9). 06/2008; 6(6):644-53. DOI: 10.1016/j.cgh.2008.03.014
Source: PubMed


We performed a meta-analysis of placebo-controlled trials to evaluate safety and efficacy of tumor necrosis factor (TNF) antagonists for Crohn's disease.
We searched MEDLINE, Cochrane Library, and EMBASE. The primary end points were clinical remission for luminal Crohn's disease and fistula closure at > or =2 consecutive visits. Deaths, serious infections, and malignancies were also analyzed by the methods of Peto and Der Simonian and Laird.
Fourteen luminal Crohn's disease trials enrolled 3995 patients. In overall analysis, anti-TNF therapy was effective for induction of remission at week 4 (mean difference, 11%; 95% confidence interval [CI], 6%-16%; P < .001) and maintenance of remission at weeks 20-30 in patients who responded to induction therapy and in patients randomized before induction (mean difference, 23%; 95% CI, 18%-28% and mean difference, 8%; 95% CI, 3%-12%, respectively; P < .001 for all comparisons). Ten studies evaluated anti-TNF for treatment of fistulizing Crohn's disease, involving 776 patients. In overall analysis, anti-TNF therapy was effective for fistula closure only in maintenance trials after open-label induction (mean difference, 16%; 95% CI, 8%-25%; P < .001). In 21 studies enrolling 5356 individuals, anti-TNF therapy did not increase the risk of death, malignancy, or serious infection.
Infliximab, adalimumab, and certolizumab are effective in luminal Crohn's disease. Efficacy of anti-TNF agents other than infliximab in treating fistulizing Crohn's disease requires additional investigations. A longer duration of follow-up and a larger number of patients are required to better assess the safety profile of TNF antagonists in Crohn's disease.

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Available from: Pierre Deltenre, Oct 01, 2015
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    • "For example , a study from the Swedish TNF-antagonist registry found that 44% of patients were still taking their initial therapy at five years, and 25% were no longer taking any TNF antagonist at all [25]. As for IBD, up to 50% of patients lose response to treatment (secondary nonresponders) and up to 30% do not respond at all (primary nonresponders) [27]. The rational for lack or loss of response is multifactorial: molecular structure of biologic drug, pharmacokinetics, pharmacodynamics, and development of anti-drug antibodies. "
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    ABSTRACT: Clinical response in patients with rheumatoid arthritis (RA) treated with biologic agents can be influenced by their pharmacokinetics and immunogenicity. The present study evaluated the concordance between serum drug and antidrug levels as well as the clinical response in RA patients treated with biological agents who experience their first disease exacerbation while being on a stable biologic treatment. 154 RA patients treated with rituximab (RTX), infliximab (IFX), adalimumab (ADL), or etanercept (ETN) were included. DAS28, SDAI, and EULAR response were assessed at baseline and reevaluated at precise time intervals. At the time of their first sign of inadequate response, patients were tested for both serum drug level and antidrug antibodies level. At the next reevaluation, patients retreated with RTX that had detectable drug level had a better EULAR response (P = 0.038) with lower DAS28 and SDAI scores (P = 0.01 and P = 0.03). The same tendency was observed in patients treated with IFX and ETN regarding EULAR response (P = 0.002 and P = 0.023), DAS28 score (P = 0.002 and P = 0.003), and SDAI score (P = 0.001 and P = 0.026). Detectable biologic drug levels correlated with a better clinical response in patients experiencing their first RA inadequate response while being on a stable biologic treatment with RTX, IFX, and ETN.
    BioMed Research International 05/2014; 2014:702701. DOI:10.1155/2014/702701 · 2.71 Impact Factor
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    • "Despite the high effectiveness of anti-TNF in patients with IBD, more than one-third of patients present primary resistance, and another one-third become resistant over time [37]. Optimal clinical response required the maintenance of clinically effective drug concentrations, but the pharmacokinetic of anti-TNF is highly variable among patients and could be influenced by numerous factors including gender, body weight, associated treatments (immunosuppressants are known to increase anti-TNF trough levels), route of administration, serum albumin concentration, and systemic inflammation with a markedly decreased half-life in patients with severe disease [38–40]. "
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    ABSTRACT: Since their appearance in the armamentarium for inflammatory bowel disease (IBD) more than a decade ago, antitumor necrosis factor (TNF) inhibitors have demonstrated beneficial activity in induction and maintenance of clinical remission, mucosal healing, improvement in quality of life, and reduction in surgeries and hospitalizations. However, more than one-third of patients present primary resistance, and another one-third become resistant over time. One of the main factors associated with loss of response is the immunogenicity of anti-TNF biologics leading to the production of antidrug antibodies (ADAbs) accelerating their clearance. In this review we present the current state of the literature on the place of TNF and its blockage in the treatment of patients with IBD and discuss the usefulness of serum trough levels and ADAb monitoring in the optimization of anti-TNF therapies.
    Mediators of Inflammation 03/2014; 2014:172821. DOI:10.1155/2014/172821 · 3.24 Impact Factor
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    • "Increased local secretion has long suggested that TNFα among other cytokines may play a role in both diseases [12, 13]. While anti-TNFα is a recognized treatment of Crohn's disease [14], it has been reported to be of clinical use in refractory or severe sarcoidosis [15]. Sarcoidosis may occur during anti-TNFα treatment of Crohn's disease [16] and other inflammatory and rheumatic diseases [17, 18] and with other drugs interfering with the cell interaction processes [19]. "
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    ABSTRACT: Sarcoidosis and Crohn's disease are systemic granulomatous disorders affecting the lung and the intestine, respectively, with variable involvement of other organs and are seldom associated. While anti-TNF α is a recognized treatment of Crohn's disease, its usage is discussed in sarcoidosis. A 42-year-old man presented with an 11-year-long history of Crohn's disease; upon discovery of an abnormal chest CT scan the diagnosis of multivisceral sarcoidosis was made and, later, a treatment with an anti-TNF α agent, infliximab, was started, because of worsening Crohn's disease recurrences. CT scan demonstrated net regression of pulmonary opacities and hepatosplenic lesions. Pathologies obtained from the intestinal tract and the bronchi of the patient were, respectively, characteristic of Crohn's disease and sarcoidosis leading to the diagnosis of both diseases. We report a rare case of steroid resistant Crohn's disease associated with multivisceral sarcoidosis, treated successfully by an anti-TNF α agent, infliximab.
    02/2014; 2014:368780. DOI:10.1155/2014/368780
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