Oncology and Transplant Unit

Rome, Italy

Oncology and Transplant Unit

Rome, Italy

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Matucci A.,a Immunoallergology Unit | Cammelli D.,a Immunoallergology Unit | Cantini F.,Misericordia e Dolce Hospital | Goletti D.,National Institute for Infectious Diseases | And 6 more authors.
Expert opinion on drug safety | Year: 2016

INTRODUCTION: Tumor necrosis factor-alpha (TNF-α) antagonists have been shown to be effective in the treatment of chronic inflammatory rheumatic conditions. The use of anti-TNF agents, combined with improved diagnosis, aggressive regimens and regular monitoring, have substantially improved patient outcomes. However, all biological agents are immunogenic, resulting in the formation of anti-drug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse. In addition, ADAs can also cause serious adverse events such as infusion hypersensitivity reactions. Areas covered: This narrative review of studies investigating the immunogenicity and clinical safety implications of TNF antagonists confirms that structural and pharmacological differences between agents results in differences in the probabilities and outcomes of immunogenicity. Expert opinion: Anti-TNF therapies have been shown to trigger auto-immune responses such as a lupus-like syndrome. Despite the fact that all biological agents have the potential for immunogenic reactions and a number of predisposing factors have been identified, the mechanisms remain to be completely clarified and the assessment of immunogenicity and its clinical relevance is matter of discussion. There are many questions regarding immunogenicity that still need answering to better optimize anti-TNF treatment in patients with chronic inflammatory rheumatic disease.


Tocci G.,University of Rome La Sapienza | Goletti D.,National Institute for Infectious Diseases | Marino V.,Pfizer | Matucci A.,Immunoallergology Unit | And 3 more authors.
Expert Opinion on Drug Safety | Year: 2016

Introduction: Many chronic rheumatic diseases have an inflammatory etiology, leading to accelerated atherosclerosis and increased occurrence of vascular diseases. In rheumatoid arthritis (RA), a reduction in cardiovascular (CV) events has been reported under treatments reducing systemic inflammation. Areas covered: Given the central role of tumour necrosis factor alpha (TNFα) in chronic inflammatory conditions and in atherosclerosis, it has been suggested that TNFα-antagonists may reduce CV risk and mortality. Although there are no randomized controlled or head-to-head trials investigating the effect of specific anti-TNF-agents on CV outcomes, observational cohort studies, national registry data, and meta-analyses in RA have reported improved CV outcomes with anti-TNF therapy. Expert opinion: It is unclear whether this is due to reduced systemic inflammation or a specific anti-TNF effect at the atherosclerotic plaque level. Observed CV benefits appear to correlate with anti-TNF response. Conversely, although inconsistently, anti-TNF agents have also been linked with increased incidence/worsening of heart failure. Additional CV adverse events with anti-TNFs include vasculitis and venous thromboembolic events. We provide an overview of the likely effects of anti-TNF therapy on CV risk and adverse events, and evaluated differences in CV outcomes among different anti-TNFagents. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Bonovas S.,a Humanitas Clinical and Research Center | Minozzi S.,Lazio Regional Health Service | Lytras T.,University Pompeu Fabra | Lytras T.,d Center for Research in Environmental Epidemiology | And 15 more authors.
Expert opinion on drug safety | Year: 2016

INTRODUCTION: Malignancies have been reported in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with anti-tumour necrosis factor (anti-TNF) agents. Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of anti-TNF agents on the occurrence of cancer (any type). Literature databases were searched up to May 2014 to identify relevant studies that evaluated adalimumab, certolizumab, etanercept, golimumab, or infliximab, compared with placebo or no treatment. Data on cancer occurrence were extracted at the maximum follow-up time reported. Expert opinion: Fifty-five RCTs with 20,631 patients met the eligibility criteria. Of these, 32 trials with 15,539 patients reported at least one case of cancer, for a total of 112 malignancies. The degree of variability between studies was consistent with what would be expected to occur by chance alone. There was no evidence of an association between anti-TNF agents and cancer risk (fixed-effects model (OR: 1.31, 95% CI: 0.89, 1.95); a random-effects model (OR: 1.16, 95% CI: 0.75, 1.81)). We found evidence of selective outcome reporting or publication bias suggesting that the pooled effect estimate for cancer may have been overestimated. The evidence is imprecise, and the risk of bias was high or unclear across primary studies.


Minozzi S.,Lazio Regional Health Service | Bonovas S.,b Humanitas Clinical and Research Center | Lytras T.,University Pompeu Fabra | Lytras T.,d Center for Research in Environmental Epidemiology | And 16 more authors.
Expert opinion on drug safety | Year: 2016

INTRODUCTION: Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.


PubMed | University of Rome La Sapienza, l Immunoallergology Unit, IRCCS Galeazzi Orthopedic Institute, University Pompeu Fabra and 9 more.
Type: Journal Article | Journal: Expert opinion on drug safety | Year: 2016

Malignancies have been reported in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with anti-tumour necrosis factor (anti-TNF) agents. Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of anti-TNF agents on the occurrence of cancer (any type). Literature databases were searched up to May 2014 to identify relevant studies that evaluated adalimumab, certolizumab, etanercept, golimumab, or infliximab, compared with placebo or no treatment. Data on cancer occurrence were extracted at the maximum follow-up time reported. Expert opinion: Fifty-five RCTs with 20,631 patients met the eligibility criteria. Of these, 32 trials with 15,539 patients reported at least one case of cancer, for a total of 112 malignancies. The degree of variability between studies was consistent with what would be expected to occur by chance alone. There was no evidence of an association between anti-TNF agents and cancer risk (fixed-effects model (OR: 1.31, 95% CI: 0.89, 1.95); a random-effects model (OR: 1.16, 95% CI: 0.75, 1.81)). We found evidence of selective outcome reporting or publication bias suggesting that the pooled effect estimate for cancer may have been overestimated. The evidence is imprecise, and the risk of bias was high or unclear across primary studies.


PubMed | National Institute for Infectious Diseases, b Humanitas Clinical and Research Center, University Pompeu Fabra, Oncology and Transplant Unit and 9 more.
Type: Journal Article | Journal: Expert opinion on drug safety | Year: 2016

Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.


PubMed | National Institute for Infectious Diseases, Pfizer, e Immunoallergology Unit, Oncology and Transplant Unit and 3 more.
Type: Journal Article | Journal: Expert opinion on drug safety | Year: 2016

Many chronic rheumatic diseases have an inflammatory etiology, leading to accelerated atherosclerosis and increased occurrence of vascular diseases. In rheumatoid arthritis (RA), a reduction in cardiovascular (CV) events has been reported under treatments reducing systemic inflammation. Areas covered: Given the central role of tumour necrosis factor alpha (TNF) in chronic inflammatory conditions and in atherosclerosis, it has been suggested that TNF-antagonists may reduce CV risk and mortality. Although there are no randomized controlled or head-to-head trials investigating the effect of specific anti-TNF-agents on CV outcomes, observational cohort studies, national registry data, and meta-analyses in RA have reported improved CV outcomes with anti-TNF therapy. Expert opinion: It is unclear whether this is due to reduced systemic inflammation or a specific anti-TNF effect at the atherosclerotic plaque level. Observed CV benefits appear to correlate with anti-TNF response. Conversely, although inconsistently, anti-TNF agents have also been linked with increased incidence/worsening of heart failure. Additional CV adverse events with anti-TNFs include vasculitis and venous thromboembolic events. We provide an overview of the likely effects of anti-TNF therapy on CV risk and adverse events, and evaluated differences in CV outcomes among different anti-TNF-agents.


PubMed | University of Rome La Sapienza, Pfizer, Oncology and Transplant Unit, University of Naples Federico II and 4 more.
Type: Journal Article | Journal: Expert opinion on drug safety | Year: 2016

Tumor necrosis factor-alpha (TNF-) antagonists have been shown to be effective in the treatment of chronic inflammatory rheumatic conditions. The use of anti-TNF agents, combined with improved diagnosis, aggressive regimens and regular monitoring, have substantially improved patient outcomes. However, all biological agents are immunogenic, resulting in the formation of anti-drug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse. In addition, ADAs can also cause serious adverse events such as infusion hypersensitivity reactions. Areas covered: This narrative review of studies investigating the immunogenicity and clinical safety implications of TNF antagonists confirms that structural and pharmacological differences between agents results in differences in the probabilities and outcomes of immunogenicity. Expert opinion: Anti-TNF therapies have been shown to trigger auto-immune responses such as a lupus-like syndrome. Despite the fact that all biological agents have the potential for immunogenic reactions and a number of predisposing factors have been identified, the mechanisms remain to be completely clarified and the assessment of immunogenicity and its clinical relevance is matter of discussion. There are many questions regarding immunogenicity that still need answering to better optimize anti-TNF treatment in patients with chronic inflammatory rheumatic disease.

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