Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. In the Ninth Edition, the JCA Special Issue Writing Committee has incorporated systematic review and evidence-based approaches in the grading of evidence and categorization of apheresis indications to make recommendations on the use of apheresis in a wide variety of diseases and conditions. This edition has largely maintained the general layout and concept of a fact sheet introduced in the Fourth Edition (2007). Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease or medical condition. The Ninth Edition of the JCA Special Issue comprises 91 fact sheets and 166 graded and categorized indications. This includes seven new fact sheets, nine new indications on existing fact sheets, and eight changes in the category for existing indications. The Ninth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

Relapsing and Progressive Complications of Severe Hypertriglyceridemia: Effective Long-Term Treatment with Double Filtration Plasmapheresis.

BACKGROUND: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. OBJECTIVES: To evaluate the use and efficacy of regular DFPP treatment in clinical practice for preventing recurrence of HTG-associated complications in thera-py refractory patients. METHODS: Retrospective multicenter study in patients with severe symptomatic drug and diet refractory HTG with regular DFPP treatment. Patients' incidence of HTG-associated pancreatic or cardiovascular complications was compared before treatment and with regular DFPP treatment. RESULTS: Ten patients (3 female) were identified with baseline maximal TG concentrations of 2,587-28,090 mg/dL (median 5,487 mg/dL; interquartile range [IQR] 4,340-12,636). The mean observation period was 3.9 ± 3.4 years before and 3.8 ± 3.0 years after commencement of DFPP. In 5 patients, severe HTG was related to chylomicronemia, 2 patients had familial partial lipodystrophy Dunnigan, and 1 patient had additional LP(a)-hyperlipoproteinemia. The main HTG-associated complication was recurrent AP in 8 patients, including 1 patient treated during pregnancy. Two patients presented severe progressive ASCVD. With long-term DFPP treatment, the annual rate of HTG-associa-ted pancreatic or cardiovascular complications declined from median 1.4 (IQR 0.7-2.6) to 0 (IQR 0.0-0.4; p < 0.005). The absolute number of events was reduced by 77%. In 6 patients (60%) episodes of AP did not occur, nor was progression of ASCVD detected clinically or by routine imaging techniques. DFPP was effective in the elimination of TG-rich LP from plasma, and was safe and well-tolerated. CONCLUSION: Long-term, regular DFPP treatment resulted in stabilization of patients with severe HTG and related recurrent AP or progression of ASCVD, who were refractory to conventional dietary and drug therapy.

Homozygous familial hypercholesterolemia with severe involvement of the aortic valve-A sibling-controlled case study on the efficacy of lipoprotein apheresis.

BACKGROUND: Homozygous familial hypercholesterolemia (hoFH) can cause severe atherosclerotic cardiovascular disease (ASCVD) in early infancy. Diagnosis and initiation of effective lipid-lowering therapy (LLT) are recommended as early as possible to prevent ASCVD-related morbidity and mortality. METHODS: The clinical courses of a pair of siblings with an identical hoFH genotype, who exhibited major similarities of their clinical phenotype were analyzed in a case-control fashion including the family. RESULTS: The older sibling was diagnosed with hoFH at the age of 4. Untreated LDL-cholesterol (LDL-C) was 17 mmol/L (660 mg/dL). LLT including lipoprotein apheresis (LA) was initiated and has been successful for 8 years now. A reduction of estimated cholesterol burden by 74% was achieved by LA and combined drug therapy including statins and ezetimibe. The efficacy of escalation of drug therapy was limited because the underlying LDL receptor (LDLR) mutation in the family resulted in substantially reduced receptor function. Treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9)-antibodies failed. His younger brother died at the age of 2 years shortly after the hoFH diagnosis of the elder sibling. Postmortem examination revealed advanced aortic root atheroma and aortic valve stenosis. In the older sibling, aortic valve stenosis and insufficiency were treated at the age of 9 years with mechanical aortic valve replacement. CONCLUSIONS: LLT including LA should be initiated as early as possible following the diagnosis of hoFH with very high LDL-C levels. With the same genotype, the phenotype of hoFH can exhibit similar patterns but outcome is substantially related to treatment.

Update to the ASFA guidelines on the use of therapeutic apheresis in ANCA-associated vasculitis.

Since 1986, the American Society for Apheresis (ASFA) has published practice guidelines on the use of therapeutic apheresis in the Journal of Clinical Apheresis (JCA) Special Issue. Since 2007, updated guidelines have been published every 3 years to reflect current evidence based apheresis practice with the most recent edition (8th) published in 2019. With each edition, the guidelines are reviewed and updated based on any newly published literature since the last review. The PEXIVAS study, an international, randomized controlled trial comparing therapeutic plasma exchange (TPE) vs no TPE and standard vs reduced dose steroid regimen on the primary composite outcome of end stage renal disease or death in patients with ANCA-associated vasculitis (AAV), was published in February 2020. This study represents the largest study on the role of therapeutic apheresis in AAV published to date and prompted the JCA Special Issue Writing Committee to reassess the current AAV fact sheet for updates based on this newly available evidence. This interim fact sheet summarizes current ASFA recommendations for the evidence-based use of therapeutic apheresis in AAV and supersedes the recommendations published in the 2019 guidelines.

Real-world study: Escalating targeted lipid-lowering treatment with PCSK9-inhibitors and lipoprotein apheresis.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid-lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long-term LA. PATIENTS AND METHODS: In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)-hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutively identified. RESULTS: Mean LDL-C concentration prior to initiation of LA or PCSK9 antibody treatment was 5.3 ± 2.6 mmol/L (205 ± 102 mg/dL). Due to established ASCVD, the risk-adjusted LDL-C target value was <1.8 mmol/L (<70 mg/dL) in all patients. Use of PCSK9 antibodies increased the proportion of patients attaining the LDL-C target concentration by 41.8% overall. Treatment emergent adverse events (TEAE) associated with PCSK9 antibody medication were reported in 35 patients (31.8%). Discontinuation of PCSK9 antibody therapy due to TEAEs occurred in 25 patients (22.7%). CONCLUSION: Finally, 55.5% of patients received a combination of PCSK9 antibody therapy and LA at individually optimized treatment frequencies resulting in an increase of target attainment in 54.1% of patients. About 18.1% of chronic LA patients terminated LA treatment in this real-world study. The termination of long-term LA therapy, which has hitherto prevented the progression of ASCVD, requires careful individual risk assessment and cannot be recommended by the general criteria of LDL-C reduction.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia-target attainment requires further increase of intensity.

BACKGROUND: Familial hypercholesterolemia (FH) causes premature cardiovascular disease (CVD). Lipoprotein apheresis (LA) is recommended as first-line lipid-lowering treatment (LLT) for homozygous (ho) FH. METHODS: Efficacy of multimodal LLT including lifestyle counseling, drug treatment, and LA was analyzed in 17 pediatric hoFH or compound heterozygous (c-het) FH patients, who commenced chronic LA in Germany before the age of 18. RESULTS: At time of diagnosis, mean low-density lipoprotein cholesterol (LDL-C) concentration was 19.6 mmol/l (756 mg/dl). Multimodal LLT resulted in 73% reduction of mean LDL-C concentration including a 62% contribution of LA. Only three children (18%) achieved mean LDL-C concentrations below the recommended pediatric target of 3.5 mmol/l (135 mg/dl). In 13 patients (76%) during chronic LA, neither cardiovascular events occurred nor was CVD progression detected clinically or by routine imaging techniques. In four patients (24%), cardiovascular events documented progression of CVD despite weekly LA, including one death due to coronary and cerebrovascular CVD which was not stabilized after commencing LA. Based on the mutational status, only 6 out of the 17 children were candidates for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition. Two already responded with further LDL-C decrease by 40%. CONCLUSIONS: Next to drug therapy, regular LA is an essential component of LLT for approaching LDL-C targets in children with hoFH or c-hetFH, which was successful only in a minority of children. Progression of CVD morbidity and resulting mortality remain unresolved issues. Early and intensified multimodal LLT guided by risk factors beyond LDL-C concentration is needed to improve outcome.

Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease: Prospective 5 Years of Follow-Up and Apolipoprotein(a) Characterization.

OBJECTIVE: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. APPROACH AND RESULTS: This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene (LPA) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter (P<0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220. CONCLUSIONS: Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients.

BACKGROUND: A marked proportion of multiple sclerosis (MS) relapses is followed by incomplete recovery. Our aim was to considerably increase the evidence of the clinical use of immunoadsorption (IA) as escalation therapy for patients with MS relapse. METHODS: A retrospective multicenter study was performed in MS patients with steroid refractory relapse who were treated with tryptophan IA. The main outcome parameter was change of acute relapse-related disability assessed by Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). IA treatments were performed using single-use tryptophan adsorbers. RESULTS: Data of 147 MS patients and 786 single IA treatments were analyzed. Treatment with IA was commenced in mean 32 ± 35 days after the onset of relapse. One hundred and five out of 147 patients (71.4%) improved functionally after mean 5.4 IA treatments within 7-10 days. EDSS improved from median 5 (interquartile range, IQR 3.5) to 4 (IQR 2.5) (p < 0.001). In patients with ON (n = 32), VA improved after the IA series in 84% of cases from median 0.2 (IQR 0.6) to 0.6 (IQR 0.66) (p < 0.001). In 98.9% of IA treatments, no clinically relevant side effect was reported. CONCLUSION: Tryptophan IA was found to be effective and well tolerated as escalation therapy for MS relapse.

Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascular disease: prospective observational multicenter study.

BACKGROUND: Lipoprotein(a) (Lp(a)) hyperlipoproteinemia is a major risk factor for cardiovascular disease, which is not affected by treatment of other cardiovascular risk factors. This study sought to assess the effect of chronic lipoprotein apheresis (LA) on the incidence of cardiovascular events in patients with progressive cardiovascular disease receiving maximally tolerated lipid-lowering treatment. METHODS AND RESULTS: In a prospective observational multicenter study, 170 patients were investigated who commenced LA because of Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease. Patients were characterized regarding plasma lipid status, lipid-lowering drug treatment, and variants at the LPA gene locus. The incidence rates of cardiovascular events 2 years before (y-2 and y-1) and prospectively 2 years during LA treatment (y+1, y+2) were compared. The mean age of patients was 51 years at the first cardiovascular event and 57 years at the first LA. Before LA, mean low-density lipoprotein cholesterol and Lp(a) were 2.56±1.04 mmol·L(-1) (99.0±40.1 mg·dL(-1)) and Lp(a) 3.74±1.63 µmol·L(-1) (104.9±45.7 mg·dL(-1)), respectively. Mean annual rates for major adverse coronary events declined from 0.41 for 2 years before LA to 0.09 for 2 years during LA (P<0.0001). Event rates including all vascular beds declined from 0.61 to 0.16 (P<0.0001). Analysis of single years revealed increasing major adverse coronary event rates from 0.30 to 0.54 (P=0.001) for y-2 to y-1 before LA, decline to 0.14 from y-1 to y+1 (P<0.0001) and to 0.05 from y+1 to y+2 (P=0.014). CONCLUSIONS: In patients with Lp(a)-hyperlipoproteinemia, progressive cardiovascular disease, and maximally tolerated lipid-lowering medication, LA effectively lowered the incidence rate of cardiovascular events. CLINICAL TRIAL REGISTRATION URL: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00003119.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking. Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies. Design: Case study. Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA. Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories. Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolemia: an expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is well established since three decades, lowering serum LDL-C levels by more than 70% per session. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment targets and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis.

BACKGROUND: In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established. METHODS: We prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients' sera. RESULTS: After the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA. CONCLUSIONS: IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.

Characteristics of carotid atherosclerotic plaques of chronic lipid apheresis patients as assessed by in vivo high-resolution CMR--a comparative analysis.

BACKGROUND: Components of carotid atherosclerotic plaques can reliably be identified and quantified using high resolution in vivo 3-Tesla CMR. It is suspected that lipid apheresis therapy in addition to lowering serum lipid levels also has an influence on development and progression of atherosclerotic plaques. The purpose of this study was to evaluate the influence of chronic lipid apheresis (LA) on the composition of atherosclerotic carotid plaques. METHODS: 32 arteries of 16 patients during chronic LA-therapy with carotid plaques and stenosis of 1-80% were matched according to degree of stenosis with 32 patients, who had recently suffered an ischemic stroke. Of these patients only the asymptomatic carotid artery was analyzed. All patients underwent black-blood 3 T CMR of the carotids using parallel imaging and dedicated surface coils. Cardiovascular risk factors were recorded. Morphology and composition of carotid plaques were evaluated. For statistical evaluation Fisher's Exact and unpaired t-test were used. A p-value <0.05 was considered statistically significant. RESULTS: Patients in the LA-group were younger (63.5 vs. 73.9. years, p<0.05), had a higher prevalence of hypercholesterolemia and of established coronary heart disease in patients and in first-degree relatives (p<0.05, respectively). LA-patients had smaller maximum wall areas (49.7 vs. 59.6mm2, p<0.05), showed lower prevalence of lipid cores (28.1% vs. 56.3%, p<0.05) and the lipid content was smaller than in the control group (5.0 vs. 11.6%, p<0.05). Minimum lumen areas and maximum total vessel areas did not differ significantly between both groups. CONCLUSION: Results of this study suggest that, despite a severer risk profile for cardiovascular complications in LA-patients, chronic LA is associated with significantly lower lipid content in carotid plaques compared to plaques of patients without LA with similar degrees of stenosis, which is characteristic of clinically stable plaques.

The German Lipoprotein Apheresis Registry-Summary of the ninth annual report.

During 2012-2020, 89 German apheresis centers collected retrospective and prospective observational data of 2028 patients undergoing regular lipoprotein apheresis (LA) for the German Lipoprotein Apheresis Registry (GLAR). More than 47 500 LA sessions are documented in GLAR. In 2020, all patients treated with LA showed a high immediate median reduction rate of LDL-C (68.2%, n = 1055) and Lp(a) (72.4%, n = 994). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to 7 years on LA (y + 1 to y + 7). During the first 2 years of LA (y + 1 and y + 2), a MACE reduction of 78% was observed. Current analysis of GLAR data shows very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid lowering medication regular by LA results.

Immunoadsorption in patients with chronic inflammatory demyelinating polyradiculoneuropathy with unsatisfactory response to first-line treatment.

BACKGROUND/AIMS: First-line treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are corticosteroids, intravenous immunoglobulin, and plasma exchange. In a significant number of patients, first-line therapy fails, and long-term maintenance treatment still remains a therapeutic challenge. Immunoadsorption (IA) may be an alternative to classical plasma exchange in the therapy of immune-mediated neurologic diseases. The aim of this investigation was to evaluate efficacy and safety of IA in patients with CIDP with unsatisfactory response to first-line treatment options. METHODS: CIDP patients received adjunct IA treatment using tryptophan-immune adsorbers. The inflammatory neuropathy cause and treatment disability (INCAT) score was used to grade disability and monitor treatment effects. RESULTS: In total, 14 CIDP patients were analyzed. Ten patients were treated in hospital. After one IA treatment series, the INCAT score decreased significantly in all 10 patients. Four of these 14 patients were treated in outpatient clinics using long-term maintenance IA with 1-2 treatments per week. In these 4 patients, effects of long-term maintenance IA resulted in an improvement of overall disability. In all patients, IA was safe, well tolerated, and no severe adverse effects occurred. CONCLUSION: IA could be an effective and safe option for CIDP patients with unsatisfactory response to first-line treatment options and for long-term maintenance treatment.

A randomized and controlled study comparing immunoadsorption and plasma exchange in myasthenic crisis.

Myasthenic crisis is the most serious life-threatening event in Myasthenia gravis patients, affecting up to 27% within the first two years after onset of disease. Extracorporeal removal of circulating autoantibodies against the nicotinic acetylcholine receptor (AChRAb) by methods of therapeutic apheresis, e.g. plasma exchange (PE) and immunoadsorption (IA) had been demonstrated as effective treatment especially in acute situations of myasthenic crisis. However, controlled data comparing clinical safety and efficacy of both methods in a clinical study were not available. Here the results of a prospective randomized controlled clinical trial are presented, investigating 19 patients with myasthenic crisis, who were randomized to receive either PE (n = 10) or IA (n = 9) in addition to combined drug treatment. Patients received 3 to 5 (mean 3.5 for PE, and 3.4 for IA) treatments over a period of 7 days with a predefined treatment volume of 1.5 l plasma (i.e., 20-25 ml/kg plasma representing 0.5-0.6 patients' plasma volumes). Clinical courses were monitored using disease specific clinical scores. After initiation of IA or PE the mean value of Myasthenia scores decreased equally until Day 14 of the post-treatment phase. Patients from both treatment groups improved to a stable clinical status of Oosterhuis Classes 1 and 2. Substantial reduction of AChRAb was documented after each session of PE or IA. In the treatment period 16 adverse effects (seven serious adverse events, SAE) in the PE and 10 (1 SAE) in the IA group were observed. In conclusion, IA proved to be equally effective compared with PE treatment in patients with myasthenic crisis. Three to five treatment sessions using low plasma volume dosage of 20-25 ml/kg were adequate to improve clinically relevant symptoms significantly in most patients.

Cardiovascular Outcome of Pediatric Patients With Bi-Allelic (Homozygous) Familial Hypercholesterolemia Before and After Initiation of Multimodal Lipid Lowering Therapy Including Lipoprotein Apheresis.

Twenty-four patients with bi-allelic familial hypercholesterolemia commencing chronic lipoprotein apheresis (LA) at a mean age of 8.5 ± 3.1 years were analysed retrospectively and in part prospectively with a mean follow-up of 17.2 ± 5.6 years. Mean age at diagnosis was 6.3 ± 3.4 years. Untreated mean LDL-C concentrations were 752 mg/dl ± 193 mg/dl (19.5 mmol/l ± 5.0 mmol/l). Multimodal lipid lowering therapy including LA resulted in a mean LDL-C concentration of 184 mg/dl (4.8 mmol/l), which represents a 75.5% mean reduction. Proprotein convertase subtilisin/kexin type 9-antibodies contributed in 3 patients to LDL-C lowering with 5 patients remaining to be tested. After commencing chronic LA, 16 patients (67%) remained clinically stable with only subclinical findings of atherosclerotic cardiovascular disease (ASCVD), and neither cardiovascular events, nor need for vascular interventions or surgery. In 19 patients (79%), pathologic findings were detected at the aortic valve (AV), which in the majority were mild. AV replacement was required in 2 patients. Mean Lipoprotein(a) concentration was 42.4 mg/dl, 38% had >50 mg/dl. There was no overt correlation of AV pathologies with other ASCVD complications, or Lipoprotein(a) concentration. Physicochemical elimination of LDL particles by LA appears indispensable for patients with bi-allelic familial hypercholesterolemia and severe hypercholesterolemia to maximize the reduction of LDL-C. In conclusion, in this rare patient group regular assessment of both the AV, as well as all arteries accessible by ultrasound should be performed to adjust the intensity of multimodal lipid lowering therapy with the goal to prevent ASCVD events and aortic surgery.

Prospective, randomized, controlled clinical study evaluating the efficacy of Rheopheresis for dry age-related macular degeneration. Dry AMD treatment with Rheopheresis Trial-ART.

PURPOSE: To evaluate Rheopheresis for the treatment of patients with high-risk dry age-related macular degeneration and no therapeutic alternative. Rheopheresis is a method of therapeutic apheresis using the methodology of double filtration plasmapheresis to treat microcirculatory disorders. METHODS: The dry AMD treatment with Rheopheresis trial (ART) was a randomised, controlled clinical study. Patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen (the fellow eye had advanced AMD) were randomly assigned in a 1:1 ratio to receive ten Rheopheresis treatments within 17 weeks or to remain untreated. The primary outcome was change in best-corrected ETDRS-visual acuity (mean logMar change) after 7.5 months compared to baseline visual acuity for both groups. RESULTS: Forty-three eyes of 43 patients (22 treatment and 21 control group) were analysed. The mean baseline BCVA in study eyes was 0.58 in the treatment group and 0.66 in the control group (n.s. p = 0.19). At the primary efficacy endpoint 7.5 months post baseline, there was a statistically significant mean difference of 0.95 ETDRS lines (p = 0.01) between the Rheopheresis and control groups. Nine percent of eyes in the group treated with Rheopheresis gained 2 or more ETDRS lines, as compared with 0% of eyes with no treatment. None of the treated patients had a loss in visual acuity in their study eyes, as compared with 24% of patients without treatment who lost 1 ETDRS line or more; 19% lost 2 ETDRS lines or more. Rheopheresis treatment was safe and well-tolerated. CONCLUSION: The results of ART provide further evidence that Rheopheresis is a safe and effective therapeutic option for high-risk patients with dry AMD and no therapeutic alternative. A series of Rheopheresis treatments can improve the natural course of AMD for selected patients.