Adverse Side Effects to Biological Agents

Pichler, Werner J.; Campi, Paolo

doi:10.1159/000104198

Cited by 46 publications

(70 citation statements)

References 33 publications

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“…The slowly decreasing clinical and endothelial response after a long initial response are all later in appearance, usually scattered after 1-2 years of infliximab therapy, resembling the occurrence of a treatment escape, likely related to the induction of antibodies vs the biological agent or to unproven changes in the cytokine network (19)(20). Remarkably, a worsening FMD was recorded both in patients with infectious or cardiovascular events and in patients with a loss of therapeutic response, thus this vascular marker of ED accompanies or sometimes precedes all these events.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Anti-TNF-α Treatments Reverse the Endothelial Dysfunction in Rheumatoid Arthritis: The Biological Coherence between Synovial and Endothelial Inflammation

Capria

Nardo

Baffetti

et al. 2010

Int J Immunopathol Pharmacol

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Rheumatoid arthritis (RA) is associated with an excess cardiovascular morbidity and mortality, related to systemic inflammation with endothelial dysfunction (ED) and impaired flow-mediated vasodilation (FMD). We assessed the FMD response to anti-TNF-a treatments in 28 RA patients, aged 49.8±15.3 years: an unpaired FMD was found in 66.7% of our cases and was restored after 6 weeks of anti-TNF-a treatment (13.5±5.3% vs 4.6±4.1 %, p < 0.05). Twenty-five percent of the infliximab patients demonstrated a long term response, compared with 60% of etanercept and 100% of adalimumab patients, after 2 years (p

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Section: Discussionmentioning

confidence: 99%

Long-Term Anti-TNF-α Treatments Reverse the Endothelial Dysfunction in Rheumatoid Arthritis: The Biological Coherence between Synovial and Endothelial Inflammation

Capria

Nardo

Baffetti

et al. 2010

Int J Immunopathol Pharmacol

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“…As not all cells are infected in PI animals, free E rns may bind and degrade BVDV dsRNA that might emerge from infected cells, as has been described for influenza virus-infected MDCK cells (Majde et al, 1998), thereby preventing continued induction of IFN synthesis in uninfected cells. As systemic IFN production is well known to lead to fever and other disease signs (Pichler, 2006), free E rns may contribute to maintaining PI animals as efficient virus replicators, which are essential for the persistence of BVDV in the cattle population.…”

mentioning

confidence: 99%

RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses

Magkouras

Mätzener

Rümenapf

et al. 2008

Journal of General Virology

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Recombinant pestivirus envelope glycoprotein E rns has been shown to interfere with dsRNAinduced interferon (IFN-a/b) synthesis. This study demonstrated that authentic, enzymically active E rns produced in mammalian cells prevented a dsRNA-induced IFN response when present in the supernatant of bovine cells. Strikingly, IFN synthesis of cells expressing E rns was eliminated after extracellular addition, but not transfection, of dsRNA. Importantly, the same applied to cells infected with bovine viral diarrhea virus (BVDV) expressing E rns but lacking the N-terminal protease N pro . Free E rns concentrations circulating in the blood of animals persistently infected with BVDV were determined to be approximately 50 ng ml "1 , i.e. at a similar order of magnitude as that displaying an effect on dsRNA-induced IFN expression in vitro. Whilst N pro blocks interferon regulatory factor-3-dependent IFN induction in infected cells, E rns may prevent constant IFN induction in uninfected cells by dsRNA that could originate from pestivirus-infected cells. This probably contributes to the survival of persistently BVDV-infected animals and maintains viral persistence in the host population.Bovine viral diarrhea virus (BVDV), a member of the family Flaviviridae and a major ubiquitous cattle pathogen, causes two fundamentally different types of infection. Animals infected post-natally are transiently infected, mostly without showing obvious disease signs such as diarrhoea and coughing (Corapi et al., 1990;Meyers & Thiel, 1996;Ridpath et al., 2000;Thiel et al., 1996). When infected in utero as a result of maternal infection, fetuses may develop and be born normally. They remain infected for life and display a highly specific immunotolerance towards the infecting viral strain (Brownlie, 1990). Immunotolerance of persistently infected (PI) animals is explained by the early time point of infection between approximately 40 and 120 days of intrauterine development. In contrast to the adaptive immune response, innate immune defence mechanisms are operative even in the early stages of intrauterine development when the fetus is invaded by BVDV, and there is broad but indirect evidence that evasion of the host's interferon (IFN) defence is a crucial prerequisite for the establishment and maintenance of persistent infection (Adler et al., 1997;Charleston et al., 2001;Schweizer & Peterhans, 2001).Over the past few years, it has become apparent that virtually all viruses express proteins that target the host's IFN defence mechanisms. Collectively, these proteins target either the induction pathways or the mechanism of IFN action (for a review, see Randall & Goodbourn, 2008). Induction of IFN is initiated by extracellular or intracellular pattern recognition receptors that sense molecular patterns that indicate viral infection (Beutler et al., 2007). In the case of positive-and negative-sense RNA viruses, dsRNA, a by-product of viral RNA replication, and 59-triphosphorylated RNA, respectively, are believed to be the most important IFN inducers ...

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“…As expected, the immune system usually responds to this chimeric monoclonal antibody as foreign antigen by producing antibodies towards different sites of the molecule, especially against the murine part (anti-mouse antibodies). Acute infusion reactions occur during, or within 24 hours after infusion, whereas a delayed reaction is defined as any adverse reaction that occurs from 24 hours to 14 days after administration (4). Although the mechanisms of these reactions are not clearly defined, it has been proposed that such reactions may be the consequence of the immune response against infliximab with the development of antibodies to infliximab itself (5).…”

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confidence: 99%

Safety and Tolerability of Infliximab Therapy: Suggestions and Criticisms Based on Wide Clinical Experience

Vultaggio

Matucci

Parronchi

et al. 2008

Int J Immunopathol Pharmacol

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Infliximab, an IgG1 monoclonal chimeric antibody against tumor necrosis factor (TNF)-α, represents the main biological drug employed for the treatment of several immuno-mediated inflammatory disorders. Infliximab infusion can be complicated by clinically heterogeneous adverse reactions, potentially interfering with the course of treatment. We analysed the adverse events recorded in 49 patients affected by different chronic inflammatory disorders (rheumatoid arthritis, seronegative spondiloarthritis, Behçet's disease, Wegener's granulomatosis, Churg-Strauss' syndrome, Cogan's disease) who were receiving a total of 709 infliximab infusions, in order to correlate the development of infliximab reactions and their features to some potential risk factors. We displayed a lower frequency of infusion reactions (1.5%; 11 out of 709 infusions) than those previously reported. However, patients suffering from rheumatoid arthritis and/or patients who underwent re-treatment after a long period, showed a higher prevalence of infliximab-related reactions. In conclusion, in our experience infliximab treatment is rarely complicated by adverse reactions which are, more importantly, almost always mild. Some good clinical practices, such as the low rate of infusion, pre-treatment with anti-histamine and prednisone in all patients, chronic immunosuppressive therapy and avoidance of long intervals between infusions may represent a combined useful strategy to reduce the frequency of infliximab reactions and to increase safety.

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Adverse Side Effects to Biological Agents

Cited by 46 publications

References 33 publications

Long-Term Anti-TNF-α Treatments Reverse the Endothelial Dysfunction in Rheumatoid Arthritis: The Biological Coherence between Synovial and Endothelial Inflammation

Long-Term Anti-TNF-α Treatments Reverse the Endothelial Dysfunction in Rheumatoid Arthritis: The Biological Coherence between Synovial and Endothelial Inflammation

RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses

Safety and Tolerability of Infliximab Therapy: Suggestions and Criticisms Based on Wide Clinical Experience

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