Efficacy and safety of infliximab and adalimumab in <scp>C</scp>rohn's disease: a single centre study

Zorzi, Francesca; Zuzzi, Sara; Onali, S.; Calabrese, Emma; Condino, G.; Petruzziello, C.; Ascolani, M.; Pallone, Francesco; Biancone, Livia

doi:10.1111/j.1365-2036.2012.05100.x

Cited by 58 publications

(51 citation statements)

References 41 publications

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“…A longitudinal * This work was supported by 973 Project Grants 2010CB833600, 2013CB911103, 2012CB724500, and 2010CB735605; National Natural Sci- study involving 93 Crohn's disease patients was performed to compare the effectiveness of Infliximab and Adalimumab. The study suggested that no obvious differences could be found in obtaining and maintaining remission (8). Another study drew a similar conclusion, claiming that the difference between Infliximab and Adalimumab is not obvious because the long term maintenance of the clinical remission between the two antibodies and their effectiveness are similar in both primary and secondary-tertiary centers (9).…”

Section: Tnf␣-targeting Therapy With the Use Of The Drugs Etanerceptmentioning

confidence: 89%

Comparison of the Inhibition Mechanisms of Adalimumab and Infliximab in Treating Tumor Necrosis Factor α-Associated Diseases from a Molecular View

Liang

Guo

et al. 2013

Journal of Biological Chemistry

129

137

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Background:The epitope and the TNF␣ inhabitation mechanism of Adalimumab remain unclear. Results: The crystal structure of the TNF␣ in complex with Adalimumab is reported at a resolution of 3.1 Å. Conclusion:The epitope of Adalimumab provided information that Adalimumab may have clinical advantage compared with Infliximab. Significance: These data reveal the Adalimumab's mechanism of TNF␣ inhibition and its advantages compared with other TNF inhibitors in clinical practice. TNF␣-targeting therapy with the use of the drugs Etanercept, Infliximab, and Adalimumab is used in the clinical treatment of various inflammatory and immune diseases. Although all of these reagents function to disrupt the interaction between TNF␣ and its receptors, clinical investigations showed the advantages of Adalimumab treatment compared withEtanercept and Infliximab. However, the underlying molecular mechanism of action of Adalimumab remains unclear. In our previous work, we presented structural data on how Infliximab binds with the E-F loop of TNF␣ and functions as a TNF␣ receptorbinding blocker. To further elucidate the variations between TNF␣ inhibitors, we solved the crystal structure of TNF␣ in complex with Adalimumab Fab. The structural observation and the mutagenesis analysis provided direct evidence for identifying the Adalimumab epitope on TNF␣ and revealed the mechanism of Adalimumab inhibition of TNF␣ by occupying the TNF␣ receptor-binding site. The larger antigenantibody interface in TNF␣ Adalimumab also provided information at a molecular level for further understanding the clinical advantages of Adalimumab therapy compared with Infliximab.TNF is an immunity-modulating cytokine required for immune processes. The unregulated activities of TNFs can lead to the development of inflammatory diseases. Excess amounts of TNF␣ expressed in cells are associated with the development of immune diseases, including rheumatoid arthritis, Crohn's disease, psoriatic arthritis, and inflammatory bowel disease (1, 2). The function of TNF␣ requires smooth interaction with its two receptors, TNF receptor 1 (TNFR1) 4 and TNF receptor 2 (TNFR2). Blocking the interaction between TNF␣ and TNFRs has successfully been developed as a therapy in treating inflammatory or autoimmune diseases (3,4). TNF␣ neutralization therapies, including the use of a soluble TNFR2-Fc recombinant (Etanercept), a mouse-human chimera mAb (Infliximab), or a human mAb (Adalimumab), have been introduced in the past decades for the management of rheumatoid arthritis and other immune diseases (5).Although all of these TNF␣ blockers function by interrupting the TNF␣-TNFR interaction, information on whether the different TNF␣ inhibitors have similar clinical efficacy remains controversial because of the lack of randomized clinical trial meta-analyses. In the early stages of clinical usage of Infliximab, its discontinuation was reported to result in loss of response. This largely affected patients who received long term treatment and later discontinued use (6). Approximately 10% of...

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Section: Tnf␣-targeting Therapy With the Use Of The Drugs Etanerceptmentioning

confidence: 89%

Comparison of the Inhibition Mechanisms of Adalimumab and Infliximab in Treating Tumor Necrosis Factor α-Associated Diseases from a Molecular View

Liang

Guo

et al. 2013

Journal of Biological Chemistry

129

137

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“…Single centre nonrandomised open-label cohort studies have shown comparable efficacy and safety between IFX and ADA at 1 year. 23 Yet, issues of small study size, the absence of randomisation, and the lack of objective assessments of disease activity preclude firm conclusions on comparative efficacy from these data. Further, one 27 and lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Systematic review with network meta‐analysis: the efficacy of anti‐TNF agents for the treatment of Crohn's disease

Stidham

Lee

Higgins

et al. 2014

Aliment Pharmacol Ther

181

107

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SummaryBackgroundAnti‐tumour necrosis factor‐alpha agents (anti‐TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown.AimTo perform a network meta‐analysis comparing the efficacy of anti‐TNF therapies in CD.MethodsAfter screening 506 studies, reviewers extracted information on 10 studies. Traditional meta‐analysis (TMA) was used to compare each anti‐TNF agent to placebo. Bayesian network meta‐analysis (NMA) was performed to compare the effects of anti‐TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated.ResultsCompared to placebo, TMA revealed that anti‐TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17–2.36 and RR: 1.43, 95% CI: 1.17–1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51–2.09 and RR: 1.68, 95% CI: 1.46–1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21–7.75). Sample size calculations suggest that adequately powered head‐to‐head comparative efficacy trials would require greater than 3000 patients.ConclusionsAll anti‐TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti‐TNF agents. Head‐to‐head trials among the anti‐TNF agents are impractical in terms of size and cost.

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“…Inflammatory bowel disease (IBD) commonly affects women of reproductive age 1 , and is often managed using drugs recognised to have potential for toxicity in adults 2,3 . Since it is unethical to test the safety of almost all drugs in pregnancy in clinical trials, the potential for teratogenicity of drugs taken during pregnancy has been a pressing and natural concern of all pregnant women or those attempting to become so.…”

Section: Introductionmentioning

confidence: 99%

Limited Risks of Major Congenital Anomalies in Children of Mothers With IBD and Effects of Medications

et al. 2014

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Efficacy and safety of infliximab and adalimumab in Crohn's disease: a single centre study

Abstract: SUMMARY BackgroundInfliximab 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.

Cited by 58 publications

References 41 publications

Comparison of the Inhibition Mechanisms of Adalimumab and Infliximab in Treating Tumor Necrosis Factor α-Associated Diseases from a Molecular View

Comparison of the Inhibition Mechanisms of Adalimumab and Infliximab in Treating Tumor Necrosis Factor α-Associated Diseases from a Molecular View

Systematic review with network meta‐analysis: the efficacy of anti‐TNF agents for the treatment of Crohn's disease

Limited Risks of Major Congenital Anomalies in Children of Mothers With IBD and Effects of Medications

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