Immunotherapy for MIS-C - IVIG, Glucocorticoids, and Biologics.
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ABSTRACT:
SUBMITTER: DeBiasi RL
PROVIDER: S-EPMC8362545 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPatients with rheumatoid arthritis (RA) are at increased risk for infection after arthroplasty, yet risks of specific biologic medications are unknown.ObjectiveTo compare risk for postoperative infection among biologics and to evaluate the risk associated with glucocorticoids.DesignRetrospective cohort study.SettingMedicare and Truven MarketScan administrative data from January 2006 through September 2015.PatientsAdults with RA who were having elective inpatient total knee or hip arthroplasty, either primary or revision, and had a recent infusion of or prescription for abatacept, adalimumab, etanercept, infliximab, rituximab, or tocilizumab before surgery.MeasurementsPropensity-adjusted analyses using inverse probability weights evaluated comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between biologics or with different dosages of glucocorticoids. Secondary analyses evaluated non-urinary tract hospitalized infections and 30-day readmissions.ResultsAmong 9911 patients treated with biologics, 10 923 surgical procedures were identified. Outcomes were similar in patients who received different biologics. Compared with an 8.16% risk for hospitalized infection with abatacept, predicted risk from propensity-weighted models ranged from 6.87% (95% CI, 5.30% to 8.90%) with adalimumab to 8.90% (CI, 5.70% to 13.52%) with rituximab. Compared with a 2.14% 1-year cumulative incidence of PJI with abatacept, predicted incidence ranged from 0.35% (CI, 0.11% to 1.12%) with rituximab to 3.67% (CI, 1.69% to 7.88%) with tocilizumab. Glucocorticoids were associated with a dose-dependent increase in postoperative risk for all outcomes. Propensity-weighted models showed that use of more than 10 mg of glucocorticoids per day (vs. no glucocorticoid use) resulted in a predicted risk for hospitalized infection of 13.25% (CI, 9.72% to 17.81%) (vs. 6.78%) and a predicted 1-year cumulative incidence of PJI of 3.83% (CI, 2.13% to 6.87%) (vs. 2.09%).LimitationResidual confounding is possible, and sample sizes for rituximab and tocilizumab were small.ConclusionRisks for hospitalized infection, PJI, and readmission after arthroplasty were similar across biologics. In contrast, glucocorticoid use, especially with dosages above 10 mg/d, was associated with greater risk for adverse outcomes.Primary funding sourceRheumatology Research Foundation, National Institutes of Health, and Bristol-Myers Squibb.
| S-EPMC7197029 | biostudies-literature
Project description:Immunotherapeutics are frequently associated with adverse side effects due to the elicitation of global immune modulation. To lower the risk of these side effects, recombinant DNA technology is employed to enhance the selectivity of cell targeting by genetically fusing different biomolecules, yielding new species referred to as multi-specific biologics. The design of new multi-specific biologics is a central challenge for the realization of new immunotherapies. To understand the molecular determinants responsible for regulating the binding between multi-specific biologics and surface-bound membrane receptors, we developed a multiscale computational framework that integrates various simulation approaches covering different timescales and spatial resolutions. Our model system of multi-specific biologics contains two natural ligands of immune receptors, which are covalently tethered by a peptide linker. Using this method, a number of interesting features of multi-specific biologics were identified. Our study therefore provides an important strategy to design the next-generation biologics for immunotherapy.
| S-EPMC7710644 | biostudies-literature
Project description:BackgroundThe responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP).MethodsBetween 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone.ResultsRegarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone.ConclusionThese findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.
| S-EPMC9058461 | biostudies-literature
Project description:Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs <20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.
| S-EPMC7160294 | biostudies-literature
Project description:Immunoglobulin therapy has a crucial role in the treatment of primary and secondary immunodeficiencies as well as in a multitude of neurologic, hematologic, infectious, and autoimmune conditions. In the current study, a preliminary pilot scale needs assessment survey was conducted to examine the need for IVIG among patients in Addis Ababa, Ethiopia, and in so doing justify local manufacturing of IVIG products. The survey was performed by administering a structured questionnaire to private and government hospitals, a national blood bank, a regulatory body, and healthcare researchers working in academia and pharmaceutical companies. The questionnaire encompassed demographics and specific IVIG-related questions designed for each institution. Responses supplied in the study provide qualitative data. Our findings indicated that IVIG has been registered by the regulatory body for use in Ethiopia and there is a demand for the product in the country. The study also highlights that patients go as far as to clandestine markets to procure IVIG products at a cheaper price. To impede such illegal routes and make the product readily accessible, a small-scale and low-cost approach such as a mini-pool plasma fractionation technique could be implemented to locally purify and prepare IVIG using plasma collected through the national blood donation program.
| S-EPMC9969427 | biostudies-literature
Project description:Intravenous immunoglobulins (IVIg) are used in the treatment of different autoimmune and inflammatory diseases, such as immune thrombocytopenia and hemolytic anemia. One of the modes of action of IVIg is preventing phagocytosis of autoantibody-opsonized blood cells by saturation of the Fc-gamma receptors of macrophages in spleen and liver. IgG contains a fixed glycan, which is in most cases biantennary, at the asparagine residue at position 297 in the Fc tail. This glycan consists of a core structure of N-acetyl glucosamine (GlcNAc) and mannose groups, variably extended with core fucose, bisecting GlcNAc as well as terminal galactose and sialic acid. This structural glycan influences the binding affinity of IgG to Fc-gamma receptors. By glyco-engineering, we generated monoclonal IgG antibodies with different Fc-tail glycans and tested both their opsonizing and blocking capacity in a phagocytosis assay of IgG-opsonized erythrocytes with human monocyte-derived macrophages. In contrast to a lack of effect in opsono-phagocytosis, these IgG glycovariants differentially inhibited the uptake of opsonized erythrocytes. The level of bisecting GlcNAc and galactosylation had unexpectedly larger impact than core fucosylation, and suggest that targeted modifications different from the core fucose may well improve the immunomodulating efficacy of IVIg treatment.
| S-EPMC6206079 | biostudies-literature
Project description:Skin and subcutaneous diseases affect millions of people worldwide, causing significant morbidity. Biologics are becoming increasingly useful for the treatment of many skin diseases, particularly as alternatives for patients who have failed to tolerate or respond to conventional systemic therapies. Biological therapies provide a targeted approach to treatment through interaction with specific components of the underlying immune and inflammatory disease processes. This review article examines the increasing evidence base for biologics in dermatology, including well-established treatments and novel agents.
| S-EPMC3816698 | biostudies-literature
Project description:BackgroundThis multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA).MethodsThis study assessed 3897 patients and 4415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2737 bDMARDs-naïve courses and 1678 bDMARDs-switched courses [59.5% of switched courses were their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [usage 42.4%], and methotrexate [MTX] dose 8.5 mg/week [usage 60.9%]). Treatment courses included abatacept (ABT; n = 663), adalimumab (ADA; n = 536), certolizumab pegol (CZP; n = 226), etanercept (ETN; n = 856), golimumab (GLM; n = 458), infliximab (IFX; n = 724), tocilizumab (TCZ; n = 851), and TOF (n = 101/only bDMARDs-switched cases). Drug discontinuation reasons (categorized into lack of effectiveness, toxic adverse events, non-toxic reasons, or remission) and rates were estimated at 36 months using Gray's test and statistically evaluated after adjusted by potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX usage, starting date, and number of switched bDMARDs) using the Fine-Gray model.ResultsCumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; P < 0.001 between agents) and the bDMARDs-switched group (from 18.9% [TCZ] to 46.1% [CZP]; P < 0.001 between agents); toxic adverse events in the bDMARDs-naïve group (from 4.6% [ABT] to 11.2% [ETN]; P < 0.001 between agents) and the bDMARDs-switched group (from 5.0% [ETN] to 15.7% [TOF]; P = 0.004 between agents); and remission in the bDMARDs-naïve group (from 2.9% [ETN] to 10.0% [IFX]; P < 0.001 between agents) and the bDMARDs-switched group (from 1.1% [CZP] to 3.3% [GLM]; P = 0.9 between agents).ConclusionsRemarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.
| S-EPMC7296929 | biostudies-literature
Project description:Colorectal cancer is the third most common cancer in the United States and second leading cause of cancer death with over 50,000 patients expected to die from their disease in 2017. For patients who present at diagnosis with advanced disease the standard treatment is systemic chemotherapy. Over the last decade a number of biologic therapies have emerged as viable treatment options for advance colorectal cancer. When these new drugs are combined with chemotherapy survival is prolonged, often without a detriment to quality of life. In this chapter we will review the most active biologic options for treatment of colorectal cancer and place them in the context of a rapidly growing field.
| S-EPMC5506285 | biostudies-literature