Equilibrium Description Explore what makes a reaction happen by colliding atoms and molecules. Design experiments with different reactions, concentrations, and temperatures. When are reactions reversible? What affects the rate of a reaction?
Reactions occur early after initiation of treatment, are generally mild and self limited, decrease and then resolve completely with repeated dosing. Infections Multiple studies in humans and animals demonstrate the importance of TNF-aas a defense against infection with intracellular organisms such as Listeria and mycobactaeria, raising concerns about the potential for increased infections with chronic TNF inhibition.
TNF is increased in the systemic circulation after administration of endotoxin or bacteria, and TNF together with IL-1 are responsible for the physiologic alterations seen in septic shock. In a human clinical trial, treatment of septic shock with etanercept resulted in increased mortality in patients with gram positive organisms.
Despite these concerns, controlled clinical trials with etanercept alone or in combination with methotrexate did not show an increase in either frequency, type or severity of infections. In one study with infliximab, however, investigators reported one death each due to tuberculosis and coccidiomycosis.
Since infliximab and etanercept have been FDA approved and available commercially, a higher than expected number of caes of TB and fungal infections have been reported.
Careful screening of patients for latent and active TB prior to intiation of anti-TNF therapy is now recommended. Careful monitoring for infection in patients treated with TNF inhibitors is also indicated.
Malignancy The immune system has an important role in surveillance for malignancy, and the role of TNFin particular, in triggering apoptosis of some tumor cell types has already been noted.
Thus, an increased risk of malignancy is of theoretical concern with chronic long-term TNF inhibition. Unfortunately, short-term clinical trials cannot adequately address this question. At 3-year follow-ups of patients treated with TNF inhibitors in clinical trials, however, no apparent increase in the rate or type of malignancies has surfaced yet.
However, definitive answers to the risk of malignancy await long-term treatment data in a wider population. Registries have been established to collect these data.
Of concern is the potential of the mouse sequence to elicit an anti-infliximab or human anti-chimeric antibody response that would limit the therapeutic efficacy. Such antibodies have indeed been found but they can be suppressed by the use of concomitant methotrexate.
The effect of these antibodies on therapeutic efficacy remains unclear. Although etanercept is composed entirely of human sequence, neoepitopes might be generated at the joining regions of the TNF receptor and the immunoglobulin Fc region which could elicit an anti-etanercept antibody response.
This does not appear to be relevant. In the two published trials, non-blocking anti-etanercept antibodies were found in only 2 patients and did not have a notable effect on efficacy. Of unclear etiology and clinical signficance is the development of low titers of anti-double stranded DNA anti-ds-DNA antibodies in patients treated with infliximab and etanercept.
Anti-ds-DNA antibodies are considered to be specific for systemic lupus erythematosus. However, in generall, patients treated with infliximab or etanercept who developed these antibodies do not exhibit lupus like illnesses.
Conclusion In vitro studies suggested that TNF is a critical and proximal mediator of the inflammatory pathway in the rheumatoid joint. Proof-of-concept for this hypothesis has now been provided by animal studies and clinical trials.
Not only does TNF inhibition dramatically reduce markers of inflammation but it also slows or halts structural damage, and these effects appear to be as potent in early disease as they are in late disease.
In human terms, these efficacies should translate to less functional disability and higher quality of life.A schematic showing the GO/RGO-based hybrid materials for energy and environmental applications along with the SCI-indexed journal publications until now (January, ), searched from ISI by the keyword of graphene oxide combined with another one listed in .
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Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
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Thus, our results are in concordance with the seminal paper by Balaban et al. (23). Here, we have shown that even small variance in the number of targets, downstream effectors, and/or cellular susceptibility is sufficient to explain a multiphasic kill curve from a conceptual point of view and should thus be the expected response of bacterial.