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Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report.

ABSTRACT: There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies on IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective was to assess the improvement in functional ability. Due to the urgency of finding therapies for post-COVID-Syndrome (PCS), we report here the interim results of the first ten patients, with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RCT), including sham apheresis, and for an RCT combining IA with B-cell depletion therapy. Trial registration number: NCT05629988.

SUBMITTER: Stein E

PROVIDER: S-EPMC10573450 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report.

Stein Elisa E Heindrich Cornelia C Wittke Kirsten K Kedor Claudia C Kim Laura L Freitag Helma H Krüger Anne A Tölle Markus M Scheibenbogen Carmen C

Journal of clinical medicine 20231009 19

There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies on IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective was to assess th ...[more]

PMID: 37835071

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Project description:BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severely debilitating condition which markedly restricts activity and function of affected people. Since the beginning of the COVID-19 pandemic ME/CFS related to post-acute COVID-19 syndrome (PACS) can be diagnosed in a subset of patients presenting with persistent fatigue 6 months after a mostly mild SARS-CoV-2 infection by fulfillment of the Canadian Consensus Criteria (CCC 2003). Induction of autoimmunity after viral infection is a mechanism under intensive investigation. In patients with ME/CFS, autoantibodies against thyreoperoxidase (TPO), beta-adrenergic receptors (ß2AR), and muscarinic acetylcholine receptors (MAR) are frequently found, and there is evidence for effectiveness of immunomodulation with B cell depleting therapy, cyclophosphamide, or intravenous immunoglobulins (IVIG). Preliminary studies on the treatment of ME/CFS patients with immunoadsorption (IA), an apheresis that removes antibodies from plasma, suggest clinical improvement. However, evidence from placebo-controlled trials is currently missing.MethodsIn this double-blinded, randomized, sham-controlled, exploratory trial the therapeutic effect of five cycles of IA every other day in patients with ME/CFS, including patients with post-acute COVID-19 chronic fatigue syndrome (PACS-CFS), will be evaluated using the validated Chalder Fatigue Scale, a patient-reported outcome measurement. A total of 66 patients will be randomized at a 2:1 ratio: 44 patients will receive IA (active treatment group) and 22 patients will receive a sham apheresis (control group). Moreover, safety, tolerability, and the effect of IA on patient-reported outcome parameters, biomarker-related objectives, cognitive outcome measurements, and physical parameters will be assessed. Patients will be hospitalized at the clinical site from day 1 to day 10 to receive five IA treatments and medical visits. Four follow-up visits (including two visits at site and two visits via telephone call) at month 1 (day 30), 2 (day 60), 4 (day 120), and 6 (day 180; EOS, end of study visit) will take place.DiscussionAlthough ME/CFS including PACS-CFS causes an immense individual, social, and economic burden, we lack efficient therapeutic options. The present study aims to investigate the efficacy of immunoadsorption and to contribute to the etiological understanding and establishment of diagnostic tools for ME/CFS.Trial registrationRegistration Number: NCT05710770 . Registered on 02 February 2023.

Project description:IntroductionPrevious observational studies assessing β2-agonist/-antagonist use on PD risk have yielded conflicting results. We evaluated the relationship between β2-agonist use and the incidence of Parkinson's disease in patients with chronic lung disease.MethodsWe performed a retrospective cohort analysis on a 20% random sample abstracted from a traditional (fee-for-service) Medicare program in the United States. Inclusion criteria were individuals over 65 years old diagnosed with asthma, COPD, and/or bronchiectasis who were enrolled in a prescription drug (standalone Part D) plan over 2007-2010 and alive through 2014. The main outcome measure was a diagnosis of Parkinson's disease over the period 2011-2014, in relation to the number of 30-day-equivalent drug claims over 2007-2010. Logistic regression analysis was performed on a sample including 236,201 Medicare beneficiaries.ResultsThe sample was 68% female, 80% white, and on average 77 years old as of 2010. Compared to non-users, β2-agonist users were more likely to be younger (76.3y versus 78.0y), smokers (40.4% versus 31.1%) and asthmatic (62.4% versus 28.3%). The odds ratio for a β2-agonist claim on PD development was 0.986 (95% CI 0.977-0.995) after adjusting for demographics, smoking history, respiratory exacerbations, comorbidities, and other drug use. Risk reductions were larger for males than females (0.974 versus 0.994, P = 0.032), and for individuals with COPD compared to those with asthma (0.968 versus 0.998, P = 0.049). Reverse causality was addressed with a Cox analysis that allowed β2-agonist use to vary from medication initiation to disease onset. By the end of the follow-up period, β2-agonist use was shown to be associated with a true protective effect against PD onset.Discussionβ2-agonist use is associated with decreased risk of PD incidence. Further investigation, possibly including clinical trials, is warranted to strengthen the evidence base supporting clinical decision-makers looking to repurpose pharmaceuticals to prevent neurodegenerative disease onset.

Project description:BACKGROUND:Cerebral palsy (CP) is the most common physical developmental disability in childhood with a prevalence of 2 to 3 per 1000 live births. β2-adrenoreceptor agonist (β2AA) are widely used for the treatment of asthma. Maternal use of β2AAs may increase the risk of adverse neuro-psychiatric health outcomes in the offspring. No study, however, has evaluated the effect of prenatal exposure to β2AAs on the risk of CP. OBJECTIVE:To examine the association between prenatal exposure to β2AAs and the risk of childhood cerebral palsy. METHODS:This population-based cohort study included all live singleton births in Denmark from January 1, 1997 to December 31, 2003. The information on outpatient prescriptions of β2AAs was extracted from Danish National Prescription Registry. Children born to mothers who used β2AAs from 30 days before pregnancy until delivery were categorized as the exposed. To differentiate the effect of β2AAs from the underlying indications, the exposure window was further extended to 2 years before pregnancy and the exposed groups were re-defined to represent different periods of exposure to maternal use of β2AAs (use only before pregnancy, use only during pregnancy, and use both before and during pregnancy). Cases of CP were identified from the Danish Cerebral Palsy Register. Logistic regression was used to estimate incidence odds ratio (OR) of CP. RESULTS:Among all the 442,278 singletons, 19,616 (4.44%) were exposed to β2AAs in utero (from 30 days before pregnancy until delivery). The risk of childhood CP was 0.21% in exposed and 0.19% in unexposed group, yielding an adjusted OR (aOR) 1.12 (95% confidence interval (CI): 0.82, 1.53). When extending the exposure time window to 2 years prior to pregnancy, no overall significant association was observed regardless of the exposure period. However, an increased risk of CP (aOR = 1.41, 95%CI: 0.92, 2.18) for maternal β2AAs use during pregnancy was observed in female offspring, especially in those born at term (aOR = 1.65, 95%CI: 1.02, 2.67). This increase was mainly attributed to an increased risk in those born to mothers who used β2AAs both before and during pregnancy (aOR = 1.81, 95%CI: 0.99, 3.33). CONCLUSIONS:We observed an association between maternal β2AAs use during pregnancy and an increased risk of CP in female offspring, but we could not rule out confounding by the underlying indications for β2AAs.

Project description:AimsImmunoadsorption with subsequent immunoglobulin G substitution (IA/IgG) represents a novel therapeutic approach in the treatment of dilated cardiomyopathy (DCM) which leads to the improvement of left ventricular ejection fraction (LVEF). However, response to this therapeutic intervention shows wide inter-individual variability. In this pilot study, we tested the value of clinical, biochemical, and molecular parameters for the prediction of the response of patients with DCM to IA/IgG.Methods and resultsForty DCM patients underwent endomyocardial biopsies (EMBs) before IA/IgG. In eight patients with normal LVEF (controls), EMBs were obtained for clinical reasons. Clinical parameters, negative inotropic activity (NIA) of antibodies on isolated rat cardiomyocytes, and gene expression profiles of EMBs were analysed. Dilated cardiomyopathy patients displaying improvement of LVEF (≥20 relative and ≥5% absolute) 6 months after IA/IgG were considered responders. Compared with non-responders (n = 16), responders (n = 24) displayed shorter disease duration (P = 0.006), smaller LV internal diameter in diastole (P = 0.019), and stronger NIA of antibodies. Antibodies obtained from controls were devoid of NIA. Myocardial gene expression patterns were different in responders and non-responders for genes of oxidative phosphorylation, mitochondrial dysfunction, hypertrophy, and ubiquitin-proteasome pathway. The integration of scores of NIA and expression levels of four genes allowed robust discrimination of responders from non-responders at baseline (BL) [sensitivity of 100% (95% CI 85.8-100%); specificity up to 100% (95% CI 79.4-100%); cut-off value: -0.28] and was superior to scores derived from antibodies, gene expression, or clinical parameters only.ConclusionCombined assessment of NIA of antibodies and gene expression patterns of DCM patients at BL predicts response to IA/IgG therapy and may enable appropriate selection of patients who benefit from this therapeutic intervention.

Dataset Information

Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report.

Publications

Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report.

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