- |||||||||| Soliris (eculizumab) / Alexion Pharma
[VIRTUAL] Incomplete Complement Inhibition in Patients with PNH on Eculizumab - 5 Year Experience from the National PNH Service Leeds (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1716;
Increasing eculizumab is costly requiring robust evidence of suboptimal complement inhibition; a positive correlation between CH50 activity and LDH values was shown however this is not sufficient to guide clinical decisions. LDH values of the incomplete blockade group were not significantly higher than those with complete blockade, suggesting the use of LDH values as an assessment of complement inhibition in patients with ongoing symptoms or transfusion requirements is not sufficient to guide eculizumab dose increases.
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[VIRTUAL] Management of Meningococcal Disease Risk in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) on Complement Inhibitors: 18 Years’ Experience from the UK National PNH Service in Leeds (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1710;
Eculizumab, the monoclonal antibody targeting C5, is the only licensed treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH) in the UK...Bexsero (MenB vaccine) vaccination (2 vaccines within first 6 months) with boosters every 5 years was added in 2015...Our most recently introduced practice of prompt treatment with ciprofloxacin if pyrexic on antibiotic prophylaxis will prevent cases like patient 7 with a penicillin resistant strain...If no response is achieved upfront or revaccination then further MenACWY vaccination is not likely to be successful. Current practice significantly mitigates the risk of meningococcal disease, however it is essential patients remain vigilant for fever, seeking immediate medical attention stating their diagnosis of PNH on complement inhibitor therapy.
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[VIRTUAL] C3 Inhibition with Pegcetacoplan in Patients with Paroxysmal Nocturnal Hemoglobinuria: Results from the Paddock and Palomino Trials (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1708;
P1, P2a, P
Both studies enrolled subjects ≥18 years old diagnosed with PNH and no prior treatment with eculizumab...Pegcetacoplan was shown to have an acceptable safety profile and was generally well tolerated in both studies. PADDOCK and PALOMINO demonstrate the therapeutic potential of pegcetacoplan in the treatment of PNH and support further evaluation in the ongoing phase 3 PRINCE trial (NCT04085601) in complement inhibitor–naïve patients.
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[VIRTUAL] Complement Regulates the Procoagulant Effects of HIT Immune Complexes (Channel 17 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1523;
We observed significant co-localization of complement with KKO ULICs in a cremaster-laser injury model in “HIT mice” and in in situ thrombi formed in uninjured vessels (data not shown). Together, these studies demonstrate an independent role for complement activation in regulating the binding and procoagulant effects of HIT ULICs and identify new non-anticoagulant therapeutic targets that could improve clinical outcomes in this otherwise potentially devastating thrombotic disorder.
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Journal: Tanning process promotes abiotic humification: separation and characterization of humic acid-like polymers complex. (Pubmed Central) - Nov 3, 2020
In the polyphenol-Maillard system, tannin was the skeleton of polymerization or polycondensation reaction, and the high content of N and the H/C value of HAL2 indicated that in adding to amino acids, proteins promoted the humification, forming industry-specific HAL polymers with a high degree of aliphatic nature. Therefore, it can be concluded that controlling the raw materials in the tannery process (especially tannins), in order to reduce the occurrence of abiotic humification may be the key to improve the efficiency of wastewater treatment.
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Journal: Eculizumab, SARS-CoV-2 and atypical hemolytic uremic syndrome. (Pubmed Central) - Nov 1, 2020
We herein report on a kidney transplant patient with aHUS on chronic eculizumab therapy that developed severe COVID-19 despite eculizumab administration early in the course of the disease. Although eculizumab was unable to prevent the development of severe endothelial cell injury, as assessed by increasing D-dimer levels from 292 to 10 586 ng/mL, the patient eventually recovered following dexamethasone and convalescent plasma administration.
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Journal: Complement and protection from tissue injury in COVID-19. (Pubmed Central) - Nov 1, 2020
However, a unique case of COVID-19 in a patient with pre-existent atypical haemolytic syndrome on chronic eculizumab therapy suggests that even early eculizumab may fail to prevent disease progression to a severe stage. Finally, preclinical studies in endotoxaemia, another hyperinflammation syndrome characterized by lung and kidney injury, suggest that cilastatin, an inexpensive drug already in clinical use, may provide tissue protection against hyperinflammation in COVID-19.
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[VIRTUAL] Paroxysmal nocturnal hemoglobinuria pnh () - Oct 31, 2020 - Abstract #EHOC2020EHOC_326;
Therapeutic strategies include terminal complement blockade and bone marrow transplantation. Eculizumab, a monoclonal antibody complement inhibitor, is highly effective and the only licensed therapy for PNH.11 The therapeutic anti-C5 antibody eculizumab (Soliris, Alexion) has proven effective in controlling intravascular hemolysis in vivo, leading to remarkable clinical benefit in a majority of PNH patients.12,13 Yet, persistent C3 activation occurring during eculizumab treatment may lead to progressive deposition of C3 fragments on affected erythrocytes and subsequent C3-mediated extravascular hemolysis, possibly limiting the hematologic benefit of anti-C5 treatment.14,15 Thus, upstream inhibition of the complement cascade seems an appropriate strategy to improve the results of current complement-targeted treatment.16,17
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Clinical, Journal: Reduced membrane attack complex formation in umbilical cord blood during Eculizumab treatment of the mother: a case report. (Pubmed Central) - Oct 31, 2020
Eculizumab, a monoclonal antibody complement inhibitor, is highly effective and the only licensed therapy for PNH.11 The therapeutic anti-C5 antibody eculizumab (Soliris, Alexion) has proven effective in controlling intravascular hemolysis in vivo, leading to remarkable clinical benefit in a majority of PNH patients.12,13 Yet, persistent C3 activation occurring during eculizumab treatment may lead to progressive deposition of C3 fragments on affected erythrocytes and subsequent C3-mediated extravascular hemolysis, possibly limiting the hematologic benefit of anti-C5 treatment.14,15 Thus, upstream inhibition of the complement cascade seems an appropriate strategy to improve the results of current complement-targeted treatment.16,17 Eculizumab treatment of the mother with end stage renal disease may cause reduced innate immunity which could render newborns more susceptible to infections.
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Biomarker, Clinical, Journal: Complement C3 vs C5 inhibition in severe COVID-19: Early clinical findings reveal differential biological efficacy. (Pubmed Central) - Oct 30, 2020
These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials.
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[VIRTUAL] De Novo Post Kidney Transplantation Thrombotic Microangiopathy () - Oct 27, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3988;
Induction immunosuppression included a total dose of 5 mg/kg of thymoglobulin and followed by initiation of tacrolimus for goal trough of 8 - 10 mg, prednisone 40 mg, and mycophenolate 1000 mg twice daily...Both recipients received one dose of eculizumab with improvement in allograft function...Discussion TMA was acquired by the donor TMA which was likely caused by ATN. It wasn't until later in the course that the final biopsy report of the donor kidney revealed TMA which confused the diagnosis of allograft kidney injury.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] An Unusual Presentation of Atypical Hemolytic Uremic Syndrome in a Patient with Skin Ulcerations () - Oct 27, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3981;
CHF-CFHR5 mutation can be negative in ~40% of the patients. In the presence of the dysregulated complement cascade, microangiopathic process and renal failure, early treatment with eculizumab is crucial in renal recovery, but the renal response to treatment can be delayed compared to the hematologic response.
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[VIRTUAL] C3 Glomerulonephritis: Can Therapy Be Individualized? () - Oct 27, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3949;
We report a case ofC4Nef and C5Nef positive C3GN treated with eculizumab...She was treated with high dose prednisone for six months with no response...Discussion We have demonstrated a case of C3GN with positive C3 adn C5Nef with cell surface activation of complement, classical and terminal complement pathway involvement. This highlights the importance of complement function studies to help aid the localization of complement pathway defect, and to individualize therapy.
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[VIRTUAL] AKI After Eculizumab Interruption in a Case of C3 Glomerulopathy () - Oct 27, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3938;
Discussion Despite looks like safe and valuable therapeutic option in patients with C3G but the response to eculizumab is heterogeneous and when to discontinue the therapy still unsolved problem as transient interruption of the therapy sometimes complicated with AKI which may be severe enough to end with ESRD like this case. Serum creatinine results during 40 months of follow up
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Efficacy and Safety of Induction Treatment with Rituximab, Mycophenolate, and Low Doses of Corticoids in Patients with ANCA-Associated Vasculitis () - Oct 27, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3921;
Induction treatment with cyclophosphamide and corticosteroids is not always effective and has adverse effects...Maintenance therapy consisted in mycophenolate and prednisone...2 patients (11%) required Eculizumab as rescue therapy...Conclusion The early use of this induction regimen was associated with excellent overall and renal survival. The safety profile and systemic nature of VAAs seems to justify the early use of immunosuppression even in those treated without available histology.
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[VIRTUAL] The Masquerading Diagnosis of Secondary Thrombotic Microangiopathy () - Oct 27, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3914;
There are current ongoing trials of the use of eculizumab in lupus nephritis, however current guidelines recommend induction treatment using cyclophosphamide and steroids. The cause of her heart failure remained unclear, thought was secondary to microvascular coronary damage from SLE.
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[VIRTUAL] C3 Glomerulonephritis: Diagnostic Challenges and Overlap Syndromes () - Oct 27, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3905;
He received a single dose of eculizumab empirically due to concern for atypical HUS, but platelet counts improved too rapidly to be consistent with eculizumab benefit...A steroid pulse was associated with an improvement in creatinine beginning on day 4 and return to baseline kidney function by day 17. Discussion Our cases highlight the variable presentation and complexity associated with accurate diagnosis of C3GN, including considerable overlap with IAGN and TTP/HUS.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Review, Journal: Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review. (Pubmed Central) - Oct 26, 2020
Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.
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Clinical, Journal: Complement blockade for TA-TMA: lessons learned from large pediatric cohort treated with eculizumab. (Pubmed Central) - Oct 24, 2020
The best GFR recovery in survivors was a median 20% lower (IQR 7.3-40.3%) than their pre-HSCT GFR. In summary, complement blockade with eculizumab is an effective therapeutic strategy for high risk TA-TMA, but some patients with severe disease lack a complete response, prompting us to propose early intervention strategies and search for additional targetable endothelial injury pathways.
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Journal: Eculizumab deposits in vessel walls in thrombotic microangiopathy. (Pubmed Central) - Oct 22, 2020
This may play a role in controlling local complement activation-associated vascular changes in these patients. Thus, IgG subclass staining by immunofluorescence is important to avoid misdiagnoses of immune-complex or monoclonal immunoglobulin deposition disease in patients with TMA who received eculizumab.
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Journal: Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome. (Pubmed Central) - Oct 22, 2020
Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, TMA is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Ultomiris IV (ravulizumab IV) / Alexion Pharma
Journal: Antibody therapy for paroxysmal nocturnal hemoglobinuria (Pubmed Central) - Oct 21, 2020
However, many issues still persist, and several new anti-complement drugs are currently under development. Hopefully, a better drug will be developed by thorough examination of what drug is best for the patient by considering not only its efficacy and safety but also its convenience.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Clinical, Journal: Different Levels of Incomplete Terminal Pathway Inhibition by Eculizumab and the Clinical Response of PNH Patients. (Pubmed Central) - Oct 16, 2020
The occurrence of extraordinary high levels of residual terminal pathway activity in PNH patients receiving Eculizumab is rare, but can impair the suppression of hemolysis. The commonly observed low levels of residual terminal pathway activity seen for most PNH patients can exacerbate during severe infections and, thus, can cause pharmacodynamic breakthrough hemolysis in PNH patients treated with Eculizumab.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal: Myasthenia Gravis and its Association With Thyroid Diseases. (Pubmed Central) - Oct 15, 2020
Eculizumab and plasmapheresis are the two new treatment options for MG, with supporting evidence of marked improvement in recent studies...In this comprehensive review article, we tried to establish an association between myasthenia gravis and Graves' disease (GD) by exploring currently available literature from PubMed. However, more studies need to be done to establish an association between pathologies.
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[VIRTUAL] Right Atrial Aspergilloma in an Immunocompetent Patient on Prednisone () - Oct 13, 2020 - Abstract #CAP2020CAP_741;
Aspergillomas, though rare, must be considered in patients who are immunocompromised or immunosuppressed. This case is remarkable in that it involved an immunocompetent patient on short-term prednisone and eculizumab therapy, with the defibrillator wire most likely acting as a nidus for the growth of aspergillus.
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[VIRTUAL] Proteinuria in Early Pregnancy: Role of sFLT-1:PlGF Ratio (On-Demand) - Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_3300;
Based on emerging evidence of alternative complement pathway activation in PEC, Eculizumab use was discussed but not pursued due to uncertain fetal viability, even with pregnancy prolongation...Further validation and widespread availability of such testing is needed to assist in management of early pregnancy complications. Figure 1: Clinical data & Jones stain showing glomerular basement membrane duplication, characteristic of TMA.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Rescue Therapy with Eculizumab for Catastrophic Antiphospholipid Syndrome in Juvenile Systemic Lupus Erythematosus (On-Demand) - Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_2876;
We present a case of juvenile systemic lupus erythematosus (SLE), who presented with CAPS, refractory to conventional treatment, but rescue with Eculizumab Case Description The patient is a 10yo female, previously diagnosis with systemic lupus erythematosus (SLE) without renal involvement and treated with hydroxychloroquine and low dose steroid, who presented with acute kidney injury and hypertensive crisis...After 7 sessions of TPE, Methylprednisone, Rituximab, and Mycophenolate Mofetil, her renal function improved and was taken off hemodialysis...Eculizumab served as a rescue therapy with good result. Our case supports the use of Eculizumab for refractory CAPS in SLE.
- |||||||||| Soliris (eculizumab) / Alexion Pharma, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Lupus Vasculopathy Successfully Treated with Eculizumab and Rituximab in an 8-Year-Old Male (On-Demand) - Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_2860;
To our knowledge, no data exists on eculizumab for treatment of lupus vasculopathy. Given our patient’s clinical improvement with these therapies, we conclude that more research is needed to define their role in treatment of patients with lupus vasculopathy.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
[VIRTUAL] A Rare Pediatric Case of Karyomegalic Tubulointerstitial Nephritis (On-Demand) - Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_2829;
Case Description A 2-year-old male with history of refractory AML received a matched unrelated donor stem-cell transplant following busulfan, fludarabine, and single fraction total body irradiation...He required ICU stay, treatment with eculizumab and two weeks of renal replacement therapy...Four months post-transplant, he was treated with cefepime, acyclovir, ibuprofen for enterococcus bacteremia and pericardial effusion...Diagnosis requires high index of suspicion and thorough pathological examination of kidney biopsy specimen. A trial of corticosteroid therapy may be considered.
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[VIRTUAL] Life Finds a Way: Two Successful Pregnancies in a Woman Without Kidneys (On-Demand) - Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_2575;
She was diagnosed with aHUS condition during her first pregnancy and was initiated on biweekly infusions of eculizumab after delivery...This article details a Saudi Arabian woman receiving intermittent peritoneal dialysis who successfully carried a pregnancy to 29 weeks, with the birth of a healthy child. This report highlights the lack of literature regarding managing pregnant patients on iHD, especially those without kidneys.
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