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Prednisone prior to ivig.Steroid sparing effect of intravenous immunoglobulin therapy in patients with pemphigus foliaceus |
Steroid sparing effect of intravenous immunoglobulin therapy in patients with pemphigus foliaceus.
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Read our disclaimer for details. Last Update Posted : September 10, See Contacts and Locations. Study Description. Show detailed description. Hide detailed description. Detailed Description:. Drug Information available for: Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate Globulin, Immune.
FDA Resources. Arms and Interventions. If well-tolerated, the infusion rate may gradually be increased to 4.
During the infusion, health care personnel are present to secure immediate action in case of serious AR. Blood pressure and pulse is monitored before, during and after the treatment. In case of anaphylaxis, the treatment is discontinued and the participant is excluded. The hospital ward possess adrenaline 0. Human albumin infusion and placebo tablets. Infusion: Initial infusion rate of 0. Outcome Measures. Primary Outcome Measures : A normal live fetus at nuchal scan in ITT population [ Time Frame: 12 week after embryo transfer ] The frequency of participants with minimum one apparently normal fetus alive at the time of nuchal scan approx.
The frequency of participants in the ITT population with minimum one apparently normal fetus alive at the time of nuchal scan approx. The frequency of participants in the PP population with minimum one apparently normal fetus alive at the time of nuchal scan approx.
Secondary Outcome Measures : Maternal adverse reactions [ Time Frame: 9 months after embryo transfer. The frequency of pregnancy losses with unknown or normal karyotype among all participants with a pregnancy loss having an evac. Number of live-born babies with a of congenital deformity among all live-borns in the ITT population.
Eligibility Criteria. If the participant plan to use egg donation in the study cycle, the previous two pregnancy losses must also have happened with the use of egg donation; however, it is not required to use the same egg donor in all three embryo transfers. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials. More Information. Publications automatically indexed to this study by ClinicalTrials. Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss after assisted reproductive technology treatment: a protocol for a randomised, double-blind, placebo-controlled trial.
BMJ Open. Fertility treatment In vitro fertilization Intravenous immunoglobulin Prednisolone Recurrent pregnancy loss. National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Phase 2. Study Type :. Interventional Clinical Trial. Estimated Enrollment :. None of the personnel with patient contact will have knowledge to the patient's allocation to active treatment or placebo group. Actual Study Start Date :. Estimated Primary Completion Date :. Estimated Study Completion Date :. Placebo Comparator: Passive treatment group Human albumin infusion and placebo tablets.
Contact: Ole Bjarne Christiansen, dr. January 8, Key Record Dates. These results thus suggest not only that HMGB1 may play an essential role in the pathogenesis of KD, but also that HMGB1 detected in the blood of KD patients may be derived from coronary arteries damaged due to acute inflammation.
Therefore, we made the following two hypotheses. All the experiments described in this study were performed using second-passage cells. The concentrations of cytokines and DEX were determined based on the results of preliminary experiments Additional files 1 and 2 : Figs. S1 and S2. We next investigated the inhibitory effects of high-dose IgG and DEX at various time points after cytokine stimulation. In addition, the combination of DEX and IgG showed the strongest anti-inflammatory effects, even though they were added later Fig.
This suggested that the elevated HMGB1 protein in the culture supernatants was not newly-synthesized protein, but passively-released protein due to cellular damage caused by the inflammatory cytokine stimulation. Those findings suggest that the amount of HMGB1 released from damaged endothelial cells might be related to the severity and complications in KD patients, but not their susceptibility to KD.
Accordingly, stratifying patients by adding the blood HMGB1 level to the existing risk score s for predicting IVIG resistance may increase the probability of success of combination therapy consisting of IVIG plus a corticosteroid. Figure 1 b. In fact, a clinical trial of an anti-TNF monoclonal antibody mAb showed clinical effectiveness, including reduced fever duration and CAL formation [ 36 ].
Stock et al. Corticosteroids are widely used as potent anti-inflammatory drugs to treat various inflammatory diseases. Therefore, synergistic effects between a corticosteroid and IgG seem likely because their anti-inflammatory mechanisms apparently involve non-overlapping pathways.
To summarize our findings, a schematic illustration is presented in Fig. We sought to elucidate the benefits of combination therapy consisting of a corticosteroid and IVIG from a mechanistic perspective, especially as an initial treatment for KD patients who are predicted to be severely resistant to IVIG. Our findings indicate the possibility of benefits arising from that combination therapy.
Most important, a corticosteroid, but not IgG, can potentially prevent inflammatory stimulus-induced coronary artery endothelial cell damage. Since such effects of a corticosteroid would probably help prevent the progression of IVIG resistance in KD, it would be better to start the combination therapy as soon as possible, especially for KD patients who are predicted to be IVIG-resistant.
KD is a systemic inflammatory disease, and leukocytes also play a crucial role in its pathogenesis. Therefore, the involvement of leukocytes cannot be considered in this model, which is a limitation of this study. Nevertheless, our present findings may, from the mechanistic viewpoint, at least partly explain the clinical effectiveness of combination therapy consisting of IVIG plus a corticosteroid for severe KD patients.
Schematic illustration of the functional benefits of combination therapy consisting of standard IVIG plus a corticosteroid for severe KD patients. All data generated or analyzed during this study are included in this published article and its supplementary information files.
Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Nationwide epidemiologic survey of Kawasaki disease in Japan, Pediatr Int. Article Google Scholar.
Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young. Am Heart Assoc Circ. Google Scholar. Uehara R, Belay ED. J Epidemiol. Ulinastatin, a urinary trypsin inhibitor, for the initial treatment of patients with Kawasaki disease: a retrospective study.
Long-term efficacy of plasma exchange treatment for refractory Kawasaki disease. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. Kawasaki disease: effect of treatment on coronary artery involvement. Risk stratification in the decision to include prednisolone with intravenous immunoglobulin in primary therapy of Kawasaki disease. Pediatr Infect Dis J. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease RAISE study : a randomised, open-label, blinded-endpoints trial.
Scand J Rheumatol. An elevated value of high mobility group box 1 is a potential marker for poor response to high-dose of intravenous immunoglobulin treatment in patients with Kawasaki syndrome. HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease.
Rheumatology Oxford. Anti-inflammatory effects of high-dose IgG on TNF-alpha-activated human coronary artery endothelial cells. Eur J Immunol. Inflammatory cytokines as predictors of resistance to intravenous immunoglobulin therapy in Kawasaki disease patients. Int J Rheum Dis. Elevated granulocyte colony-stimulating factor levels predict treatment failure in patients with Kawasaki disease. J Allergy Clin Immunol. Expression of thymus and activation-regulated chemokine TARC by human dermal cells, but not epidermal keratinocytes.
J Dermatol Sci. The interleukin-1 family: back to the future. Activation and regulation of the inflammasomes. Nat Rev Immunol. Neutralizing antibodies to granulocyte-macrophage colony-stimulating factor, interleukin-1alpha and interferon-alpha but not other cytokines in human immunoglobulin preparations.
Protective effect of spironolactone on endothelial cell apoptosis. Statin-induced apoptosis of vascular endothelial cells is blocked by dexamethasone. J Endocrinol. HMGB1 as a late mediator of lethal systemic inflammation. High mobility group 1 protein HMG-1 stimulates proinflammatory cytokine synthesis in human monocytes.
J Exp Med. The potential effect and mechanism of high-mobility group box 1 protein on regulatory T cell-mediated immunosuppression. J Interf Cytokine Res. High mobility group box-1 protein regulate immunosuppression of regulatory T cells through toll-like receptor 4. Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease. Genome Med. A child with severe relapsing Kawasaki disease rescued by IL-1 receptor blockade and extracorporeal membrane oxygenation.
Ann Rheum Dis. High dose Anakinra for treatment of severe neonatal Kawasaki disease: a case report. Pediatr Rheumatol Online J. Review: found in translation: international initiatives pursuing Interleukin-1 blockade for treatment of acute Kawasaki disease. Arthritis Rheum.
Pediatric Rheumatology volume 18Article number: 76 Cite this article. Metrics details. Kawasaki disease KD is the most common pediatric systemic vasculitides of unknown etiology. Recent clinical studies led to reappraisal of the usefulness of initial combination therapy of intravenous immunoglobulin IVIG plus a corticosteroid for patients with severe KD.
However, the molecular mechanisms underlying the clinical benefits of that combination therapy remain unclear. Here, we used cultured human coronary artery endothelial cells HCAECsas a mimic of KD, to study the possible mechanisms responsible for the clinical benefits of adding a corticosteroid to standard IVIG therapy for patients with severe KD. Kawasaki disease KDfirst described by Dr. Tomisaku Kawasaki in in Japan [ 1 ], is one of the most common pediatric systemic vasculitides of unknown etiology.
Since that first report, the morbidity rate of KD in Japan has continued to rise, and currently, there are more than 15, new patients annually [ 2 ]. The most serious clinical issue in KD is the formation of coronary artery lesions CALs due to severe inflammation of the coronary arteries. The most common cause of acquired heart disease in childhood in developed countries is cardiovascular complications due to KD [ 4 ].
Looking back on the history of medical treatments for KD, corticosteroids, which are anti-inflammatory agents, were widely used prior to the establishment of standard IVIG therapy. However, corticosteroid monotherapy was subsequently reported to cause progression of CALs in some KD patients [ 8 ], and its use was long contraindicated.
However, a retrospective study by Kobayashi et al. That was especially true when the target patients were limited to severe KD, defined by a risk score predicting IVIG unresponsiveness [ 10 ].
Subsequent to that retrospective investigation [ 9 ], a randomized controlled study RAISE study demonstrated that initial combination therapy consisting of IVIG plus a corticosteroid for severe patients significantly reduced both the frequency of CAL formation and IVIG refractoriness [ 11 ].
That series of clinical studies led to reappraisal of the usefulness of initial combination therapy of IVIG plus a corticosteroid for patients with severe KD. These results thus suggest not only that HMGB1 may play an essential role in the pathogenesis of KD, but also that HMGB1 detected in the blood of KD patients may be derived from coronary arteries damaged due to acute inflammation. Therefore, we made the following two hypotheses.
All the experiments described in this study were performed using second-passage cells. The concentrations of cytokines and DEX were determined based on the results of preliminary experiments Additional files 1 and 2 : Figs. S1 and S2. We next investigated the inhibitory effects of high-dose IgG and DEX at various time points after cytokine stimulation.
In addition, the combination of DEX and IgG showed the strongest anti-inflammatory effects, even though they were added later Fig. This suggested that the elevated HMGB1 protein in the culture supernatants was not newly-synthesized protein, but passively-released protein due to cellular damage caused by the inflammatory cytokine stimulation.
Those findings suggest that the amount of HMGB1 released from damaged endothelial cells might be related to the severity and complications in KD patients, but not their susceptibility to KD. Accordingly, stratifying patients by adding the blood HMGB1 level to the existing risk score s for predicting IVIG resistance may increase the probability of success of combination therapy consisting of IVIG plus a corticosteroid.
Figure 1 b. In fact, a clinical trial of an anti-TNF monoclonal antibody mAb showed clinical effectiveness, including reduced fever duration and CAL formation [ 36 ]. Stock et al. Corticosteroids are widely used as potent anti-inflammatory drugs to treat various inflammatory diseases. Therefore, synergistic effects between a corticosteroid and IgG seem likely because their anti-inflammatory mechanisms apparently involve non-overlapping pathways.
To summarize our findings, a schematic illustration is presented in Fig. We sought to elucidate the benefits of combination therapy consisting of a corticosteroid and IVIG from a mechanistic perspective, especially as an initial treatment for KD patients who are predicted to be severely resistant to IVIG.
Our findings indicate the possibility of benefits arising from that combination therapy. Most important, a corticosteroid, but not IgG, can potentially prevent inflammatory stimulus-induced coronary artery endothelial cell damage.
Since such effects of a corticosteroid would probably help prevent the progression of IVIG resistance in KD, it would be better to start the combination therapy as soon as possible, especially for KD patients who are predicted to be IVIG-resistant. KD is a systemic inflammatory disease, and leukocytes also play a crucial role in its pathogenesis.
Therefore, the involvement of leukocytes cannot be considered in this model, which is a limitation of this study. Nevertheless, our present findings may, from the mechanistic viewpoint, at least partly explain the clinical effectiveness of combination therapy consisting of IVIG plus a corticosteroid for severe KD patients. Schematic illustration of the functional benefits of combination therapy consisting of standard IVIG plus a corticosteroid for severe KD patients.
All data generated or analyzed during this study are included in this published article and its supplementary information files. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Nationwide epidemiologic survey of Kawasaki disease in Japan, Pediatr Int.
Article Google Scholar. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young.
Am Heart Assoc Circ. Google Scholar. Uehara R, Belay ED. J Epidemiol. Ulinastatin, a urinary trypsin inhibitor, for the initial treatment of patients with Kawasaki disease: a retrospective study. Long-term efficacy of plasma exchange treatment for refractory Kawasaki disease.
Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. Kawasaki disease: effect of treatment on coronary artery involvement. Risk stratification in the decision to include prednisolone with intravenous immunoglobulin in primary therapy of Kawasaki disease.
Pediatr Infect Dis J. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease RAISE study : a randomised, open-label, blinded-endpoints trial.
Scand J Rheumatol. An elevated value of high mobility group box 1 is a potential marker for poor response to high-dose of intravenous immunoglobulin treatment in patients with Kawasaki syndrome. HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease. Rheumatology Oxford. Anti-inflammatory effects of high-dose IgG on TNF-alpha-activated human coronary artery endothelial cells.
Eur J Immunol. Inflammatory cytokines as predictors of resistance to intravenous immunoglobulin therapy in Kawasaki disease patients. Int J Rheum Dis. Elevated granulocyte colony-stimulating factor levels predict treatment failure in patients with Kawasaki disease. J Allergy Clin Immunol. Expression of thymus and activation-regulated chemokine TARC by human dermal cells, but not epidermal keratinocytes. J Dermatol Sci. The interleukin-1 family: back to the future. Activation and regulation of the inflammasomes.
Nat Rev Immunol. Neutralizing antibodies to granulocyte-macrophage colony-stimulating factor, interleukin-1alpha and interferon-alpha but not other cytokines in human immunoglobulin preparations. Protective effect of spironolactone on endothelial cell apoptosis. Statin-induced apoptosis of vascular endothelial cells is blocked by dexamethasone. J Endocrinol. HMGB1 as a late mediator of lethal systemic inflammation.
High mobility group 1 protein HMG-1 stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. The potential effect and mechanism of high-mobility group box 1 protein on regulatory T cell-mediated immunosuppression.
J Interf Cytokine Res. High mobility group box-1 protein regulate immunosuppression of regulatory T cells through toll-like receptor 4. Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease. Genome Med. A child with severe relapsing Kawasaki disease rescued by IL-1 receptor blockade and extracorporeal membrane oxygenation. Ann Rheum Dis. High dose Anakinra for treatment of severe neonatal Kawasaki disease: a case report. Pediatr Rheumatol Online J. Review: found in translation: international initiatives pursuing Interleukin-1 blockade for treatment of acute Kawasaki disease.
Arthritis Rheum. Clin Immunol Immunopathol. Clin Exp Immunol. TNF-alpha is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of Kawasaki disease. J Immunol. Etanercept suppresses arteritis in a murine model of Kawasaki disease: a comparative study involving different biological agents.
Currently there is class A evidence to use IVIG to treat exacerbations of MG. In addition, some authors recommend IVIG or PLEX before thymectomy. The following information was recorded in each patient, before and after IVIg therapy initiation: total dose and total duration of prednisone therapy. Before IVIg therapy was initiated, the dosage of prednisone therapy ranged from 80 to mg/d (mean, mg/d), the total dose ranged from to 90 Intravenous immunoglobulin(IVIg) and prednisolone. IVIG is administered at the time of embryo/blastocyst transfer (ET) (5 days before to 2 days after ET) and if. Infusions of intravenous immunoglobulin (IVIG) given before high-dose prednisone safely prevents most of its associated exacerbations in people. However, the molecular mechanisms underlying the clinical benefits of that combination therapy remain unclear. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young. Long-term efficacy of plasma exchange treatment for refractory Kawasaki disease. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. To gain access, data requestors will need to sign a data access agreement. Search all BMC articles Search.Pemphigus foliaceus PF is a rare autoimmune cutaneous blistering disease, with only skin involvement. Systemic corticosteroids and immunosuppressive agents are the mainstay of therapy. However, some patients develop multiple side effects to systemic corticosteroids, when they are used in high doses over prolonged periods. In some patients, immunosuppressive agents are not effective or contraindicated.
In such patients, alternative treatment modalities are needed. The purpose of this study is to demonstrate the use of intravenous immunoglobulin IVIg therapy in seven patients with severe PF, who were steroid-dependent. The following information was recorded in each patient, before and after IVIg therapy initiation: total dose and total duration of prednisone therapy, and number of relapses.
In addition, the highest dose and side effects of prednisone therapy, and duration of observation were documented. After the initiation of IVIg treatment, doses of systemic corticosteroids were gradually reduced and eventually discontinued over a mean period of 2.
Thereafter, IVIg was used as monotherapy. In all seven patients, IVIg produced an effective clinical response and demonstrated a steroid-sparing effect.
In patients with PF, who are steroid-dependent and in whom use of conventional immunosuppressive agents is contraindicated, IVIg appears a safe and effective agent to induce and maintain a prolonged clinical remission. Abstract Pemphigus foliaceus PF is a rare autoimmune cutaneous blistering disease, with only skin involvement.
Substances Glucocorticoids Immunoglobulins, Intravenous Prednisone.
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