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Experimental and Clinical... Oct 2023A common complication after transplant is an opportunistic infection, in part due to the necessary immunosuppression regimens that patients are placed on. This study...
OBJECTIVES
A common complication after transplant is an opportunistic infection, in part due to the necessary immunosuppression regimens that patients are placed on. This study aimed to assess the outcomes and rates of infection in kidney transplant recipients on belatacept compared with kidney transplant recipients on standard immunosuppression therapy.
MATERIALS AND METHODS
We conducted a matched-pair case-control retrospective analysis of a prospectively recollected database of all adult kidney transplant patients at the SUNY Upstate Medical Hospital from January 1, 2016, to July 31, 2022.
RESULTS
Among study patients, 60.5% of patients in the belatacept group and 47.9% of patients in the standard immunosuppression regimen group were diagnosed with an infectious disease during follow-up, although no significant difference was shown between the 2 groups (P = .21). The most common infection in both groups was urinary tract infection, which was comparable between the groups (41.8% vs 50%; P = .42). No significant difference was shown between patients with early and late conversion to belatacept in terms of infection incident and type.
CONCLUSIONS
Kidney transplant recipients who were converted to belatacept because of poor renal function had a similar infection rate compared with patients on standard immunosuppression treatment. Neither conversion to belatacept nor timing of conversion changed the risk of infection after kidney transplant. Our findings suggest that physicians may convert a kidney transplant recipient with poor renal function to belatacept without changing the patient's risk of opportunistic infection.
Topics: Adult; Humans; Abatacept; Kidney Transplantation; Immunosuppressive Agents; Calcineurin Inhibitors; Retrospective Studies; Graft Rejection; Graft Survival; Opportunistic Infections; Transplant Recipients
PubMed: 37965954
DOI: 10.6002/ect.2023.0137 -
Cell Communication and Signaling : CCS Nov 2023Beyond the encouraging results and broad clinical applicability of immune checkpoint (ICP) inhibitors in cancer therapy, ICP-based immunotherapies in the context of... (Review)
Review
Beyond the encouraging results and broad clinical applicability of immune checkpoint (ICP) inhibitors in cancer therapy, ICP-based immunotherapies in the context of autoimmune disease, particularly multiple sclerosis (MS), have garnered considerable attention and hold great potential for developing effective therapeutic strategies. Given the well-established immunoregulatory role of ICPs in maintaining a balance between stimulatory and inhibitory signaling pathways to promote immune tolerance to self-antigens, a dysregulated expression pattern of ICPs has been observed in a significant proportion of patients with MS and its animal model called experimental autoimmune encephalomyelitis (EAE), which is associated with autoreactivity towards myelin and neurodegeneration. Consequently, there is a rationale for developing immunotherapeutic strategies to induce inhibitory ICPs while suppressing stimulatory ICPs, including engineering immune cells to overexpress ligands for inhibitory ICP receptors, such as program death-1 (PD-1), or designing fusion proteins, namely abatacept, to bind and inhibit the co-stimulatory pathways involved in overactivated T-cell mediated autoimmunity, and other strategies that will be discussed in-depth in the current review. Video Abstract.
Topics: Animals; Humans; Multiple Sclerosis; Encephalomyelitis, Autoimmune, Experimental; T-Lymphocytes; Immunotherapy; Autoimmunity
PubMed: 37946301
DOI: 10.1186/s12964-023-01289-9 -
Rheumatology Advances in Practice 2023RA is an autoimmune disease characterized by chronic inflammation and joint destruction. Biologics are crucial to achieving treat-to-target goals in patients with RA....
OBJECTIVES
RA is an autoimmune disease characterized by chronic inflammation and joint destruction. Biologics are crucial to achieving treat-to-target goals in patients with RA. The global spread and continuous variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate the monitoring of variant-specific humoral responses post-vaccination. The aim of this study was to investigate how different biologic treatments for vaccinated RA patients might affect their neutralizing antibodies against multiple SARS-CoV-2 variants.
METHODS
We recruited RA patients who had received three doses of conventional SARS-CoV-2 vaccines and were treated with various biologics, e.g. TNF inhibitor (etanercept), IL-6 inhibitor (tocilizumab), CTLA4-Ig (abatacept) or anti-CD20 (rituximab). Serum samples were used to profile the binding and neutralizing antibodies using our own SARS-CoV-2 variant (CoVariant) protein array, developed previously.
RESULTS
Compared with healthy controls, only RA therapy with rituximab showed a reduction in neutralizing antibodies capable of targeting spike proteins in SARS-CoV-2 wild-type and most variants. This reduction was not observed in binding antibodies against SARS-CoV-2 wild-type or its variants.
CONCLUSION
After receiving three doses of SARS-CoV-2 vaccination, RA patients who underwent rituximab treatment generated sufficient antibodies but exhibited lower neutralizing activities against wild-type and multiple variants, including current Omicron. Other biological DMARDs, e.g. TNF inhibitor, IL-6 inhibitor and CTLA4-Ig, did not show obvious inhibition.
PubMed: 37937178
DOI: 10.1093/rap/rkad085 -
Annals of the Rheumatic Diseases Jan 2024This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA).
METHODS
This evaluation included 16 abatacept RA clinical trials and 6 observational studies. NMSC incidence rates (IRs)/1000 patient-years (p-y) of exposure were compared between patients treated with abatacept versus placebo, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biological/targeted synthetic (b/ts)DMARDs. For observational studies, a random-effects model was used to pool rate ratios (RRs).
RESULTS
~49 000 patients receiving abatacept were analysed from clinical trials (~7000) and observational studies (~42 000). In randomised trials (n=4138; median abatacept exposure, 12 (range 2-30) months), NMSC IRs (95% CIs) were not significantly different for abatacept (6.0 (3.3 to 10.0)) and placebo (4.0 (1.3 to 9.3)) and remained stable throughout the long-term, open-label period (median cumulative exposure, 28 (range 2-130 months); 21 335 p-y of exposure (7044 patients over 3 years)). For registry databases, NMSC IRs/1000 p-y were 5-12 (abatacept), 1.6-10 (csDMARDs) and 3-8 (other b/tsDMARDs). Claims database IRs were 19-22 (abatacept), 15-18 (csDMARDs) and 14-17 (other b/tsDMARDs). Pooled RRs (95% CIs) from observational studies for NMSC in patients receiving abatacept were 1.84 (1.00 to 3.37) vs csDMARDs and 1.11 (0.98 to 1.26) vs other b/tsDMARDs.
CONCLUSIONS
Consistent with the warnings and precautions of the abatacept label, this analysis suggests a potential increase in NMSC risk with abatacept use compared with csDMARDs. No significant increase was observed compared with b/tsDMARDs, but the lower limit of the 95% CI was close to unity.
Topics: Humans; Abatacept; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Incidence; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 37932010
DOI: 10.1136/ard-2023-224356 -
Cureus Sep 2023Felty syndrome is characterized by a triad of rheumatoid arthritis, neutropenia, and splenomegaly that typically occurs in patients with seropositive rheumatoid...
Felty syndrome is characterized by a triad of rheumatoid arthritis, neutropenia, and splenomegaly that typically occurs in patients with seropositive rheumatoid arthritis. We report a case of an 81-year-old man with a 22-year history of rheumatoid arthritis who developed pancytopenia and neutropenia for one month. An abdominal ultrasound revealed splenomegaly. A bone marrow biopsy excluded large granular lymphocytic leukemia, thus Felty Syndrome was diagnosed. He was treated with a maximum tolerated dose of methotrexate (15 mg once a week) for two months with no improvement in absolute neutrophil count. The patient was given abatacept 1000 mg intravenously every four weeks with improvement in hemoglobin, leukocyte, and platelet counts and absolute neutrophil counts from 0.2 to 2.4 K/µl.
PubMed: 37900492
DOI: 10.7759/cureus.46086 -
RMD Open Oct 2023We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).
METHODS
PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI.
RESULTS
A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=-4.62, 95% CI -8.90 to -0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively.
CONCLUSION
ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD.
PROSPERO REGISTRATION NUMBER
CRD42022356816.
Topics: Humans; Rituximab; Antirheumatic Agents; Arthritis, Rheumatoid; Lung Diseases, Interstitial; Abatacept
PubMed: 37899093
DOI: 10.1136/rmdopen-2023-003487 -
Journal of Clinical Medicine Oct 2023Rheumatoid arthritis (RA) is a chronic autoimmune multisystem inflammatory disease in which lung involvement is the most common extra-articular manifestation.... (Review)
Review
Rheumatoid arthritis (RA) is a chronic autoimmune multisystem inflammatory disease in which lung involvement is the most common extra-articular manifestation. Parenchymal lung involvement or interstitial lung disease (ILD) is a significant cause of morbidity and mortality and there is a paucity of evidence-based guidance on how to best treat RA-ILD. This review article aims to evaluate the evidence from cohort studies and best real word data from registries. Extensive discussion of the relative merits and drawbacks of glucocorticoids, various biologics, small molecules and anti-fibrotics is presented. The limited available guidelines in RA-ILD are also discussed and a rational treatment algorithm is offered.
PubMed: 37892795
DOI: 10.3390/jcm12206657 -
Diabetes Care Nov 2023
Randomized Controlled Trial
Comment on Russell et al. Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial. Diabetes Care 2023;46:1005-1013.
Topics: Humans; Diabetes Mellitus, Type 1; Abatacept; Diabetes Mellitus, Type 2; Double-Blind Method
PubMed: 37890102
DOI: 10.2337/dc23-1115 -
Cureus Sep 2023Cardiac sarcoidosis (CS) is a rare auto-immune disorder where immune cells form granulomas in the heart that may lead to potential arrhythmias and heart failure. Due to...
Cardiac sarcoidosis (CS) is a rare auto-immune disorder where immune cells form granulomas in the heart that may lead to potential arrhythmias and heart failure. Due to the low prevalence of CS, the management remains challenging, requiring a multidisciplinary approach. In addition to the management of the resulting arrhythmias and heart failure, corticosteroids and immunosuppressants are used as anti-inflammatories to prevent disease progression. Immunosuppressive regimens for the treatment of CS are not yet well established. Abatacept has been approved for rheumatoid arthritis and psoriatic arthritis and both are mainly Th1-driven autoimmune diseases. Even though there are several different drugs used to treat corticosteroid-dependent sarcoidosis, abatacept may represent a unique option as its side effects differ from other drugs like methotrexate, azathioprine, or mycophenolate, especially bone marrow and liver toxicity. We present the case of a 52-year-old CS patient treated with abatacept after the failure of methotrexate and mycophenolate mofetil. Our patient had a history of stage D heart failure with reduced ejection fraction (HFrEF) with ejection fraction (EF) of 15-20%, nonischemic cardiomyopathy (NICM) s/p left heart catheterization (LHC), CS diagnosed by positron emission tomography (PET), status post implantable cardioverter-defibrillator (ICD) implantation, lung sarcoid, paroxysmal atrial fibrillation, and aflutter, who followed with cardiology, rheumatology, and pulmonology. He had multiple admissions for heart failure exacerbations. The patient was initially diagnosed with pulmonary sarcoidosis after which he completed a small course of steroids. CT chest showed lymphadenopathy; however, endobronchial ultrasound (EBUS) did not show evidence of pulmonary sarcoidosis. During an admission for heart failure about four years later, cardiac PET CT showed CS, and rheumatology was brought on board. The patient initially refused steroids and steroid-sparing agents. At subsequent visits, the patient was amenable to medication and was started on methotrexate 10mg weekly. However, given worsening chronic kidney disorder, methotrexate was discontinued and mycophenolate 200mg daily was started. A couple of weeks after mycophenolate was started, the patient felt like "his throat was closing up" and his stomach was cramping, which was thought to be an allergic response to the mycophenolate so it was discontinued. He then received an abatacept infusion which he tolerated well. Currently, our patient has been referred for heart transplantation.
PubMed: 37876386
DOI: 10.7759/cureus.45805 -
Frontiers in Immunology 2023Combined immunotherapy has shown promising results in the treatment of advanced HCC, whereas the priority population that would respond to the combined immunotherapy is...
Case Report: Durable complete response of metastatic hepatocellular carcinoma with asymptomatic hyperamylasemia to combined immunotherapy of anti-cytotoxic T lymphocyte-associated antigen 4 plus anti-programmed cell death-1 antibodies.
BACKGROUND
Combined immunotherapy has shown promising results in the treatment of advanced HCC, whereas the priority population that would respond to the combined immunotherapy is still elusive. In addition, HCC with asymptomatic hyperamylasemia was not reported previously.
CASE PRESENTATION
An aged patient was diagnosed as HCC with BCLC stage C (bone metastasis). Notably, this patient showed asymptomatic hyperamylasemia. The patient was then enrolled in a trial evaluating combined immunotherapy of anti-PD-1 antibody sintilimab (IBI308) plus anti-CTLA-4 antibody (IBI310) in advanced HCC. After being treated with combined immunotherapy, this patient rapidly achieved complete response (CR) according to mRECIST criteria or immune partial response (iPR) according to iRECIST criteria and maintain the CR state for more than 12 months. Interestingly, serum levels of amylase and lipase in this patient were reduced after treatment.
CONCLUSION
We reported, for the first time, a case of metastatic HCC with asymptomatic hyperamylasemia, and suggested that HCC patients with asymptomatic hyperamylasemia may benefit from combined immunotherapy of anti-CTLA-4 and PD-1 antibodies.
Topics: Humans; Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Hyperamylasemia; Antibodies, Monoclonal; Immunotherapy; Abatacept; T-Lymphocytes; Cell Death
PubMed: 37869012
DOI: 10.3389/fimmu.2023.1274449