- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, Soliris (eculizumab) / AstraZeneca
Clinical, Review, Journal: Recent progress in maintenance treatment of neuromyelitis optica spectrum disorder. (Pubmed Central) - Nov 6, 2021
Tocilizumab and rituximab were also superior to azathioprine in head-to-head studies. Rituximab, tocilizumab and to some extent eculizumab have well-known safety profiles for other inflammatory diseases, and rituximab and azathioprine may be safe during pregnancy.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Journal: Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome and Membranoproliferative Glomerulonephritis. (Pubmed Central) - Nov 6, 2021
Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases...The FD inhibitor danicopan abrogated C3 convertase-associated FB cleavage to the Bb fragment in patient serum, and of the FB constructs, D371G, E601K, I242L, the gain-of-function mutation D279G, and the wild-type construct, in FB-depleted serum...In FB-depleted serum the D371G and D279G mutants induced release of C5b-9 from glomerular endothelial cells that was reduced by the FD-inhibitor. These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations.
- |||||||||| Darzalex IV (daratumumab) / J&J, Soliris (eculizumab) / AstraZeneca
Carfilzomib Is Safe in Elderly Patients with Multiple Myeloma but Thrombotic Microangiopathy Is Underestimated in Clinical Practice (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5494;
Until the end of the study, 13 CVAEs (13.5%) of grade ≥3 were observed, including 2 (11.1%), 1 (11.1%), and 10 (15.2%) in patients who received Kd (Cfz and dexamethasone), DKd (Daratumumab, Cfz, and dexamethasone), and KRd (Cfz, lenalidomide, and dexamethasone), respectively...Eculizumab was administered in a patient and a kidney biopsy showed that the lumen of most glomerular capillaries was occluded by fibrin thrombi (Fig...The incidence of CVAEs by Cfz in elderly patients was similar to that in the entire cohort. The incidence of TMA was 5.2%, and Cfz-induced TMA should be carefully considered, particularly in patients using high-dose Cfz.
- |||||||||| Darzalex IV (daratumumab) / J&J, Soliris (eculizumab) / AstraZeneca
Mutations in the Alternative Complement Pathway in Multiple Myeloma Patients with Carfilzomib-Induced Thrombotic Microangiopathy (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4349;
Regimens included carfilzomib-dexamethasone (Kd, 7 patients), carfilzomib-lenalidomide-dexamethasone (KRd, 1 patient), carfilzomib-pomalidomide-dexamethasone (KPd, 1 patient), and carfilzomib-daratumumab-dexamethasone (DaraKd, 1 patient)...Carfilzomib was discontinued in all patients and five patients were treated with plasma exchange (PLEX) while one patient received eculizumab...In the setting of carfilzomib use, heterozygous CFHR3-CFHR1 deletion may represent a risk factor for the development of TMA. Our data set the bases for larger studies assessing complement mutation as a predisposing factor for PI-induced TMA.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Post Hoc Analysis of the Effect of Pegcetacoplan Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria and Baseline Hemoglobin Levels Greater Than 10 Grams per Deciliter (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3809;
P1, P3
While these patients had near normal Hb at baseline, they also had elevated ARC prior to PEG therapy, suggesting ongoing hemolysis. Improvements in mean Hb level, Hb response, ARC, LDH level, and FACIT-Fatigue score suggest that PEG is effective in this subgroup resulting in a decline in overall hemolytic activity and a clinically significant improvement in fatigue.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Vaxzevria (ChAdOx1-S recombinant) / Oxford Biomedica, Emergent Biosolutions, Jenner Institute, Vaccitech, AstraZeneca, University of Oxford
Sars-Cov-2 Vaccination in Patients with Paroxysmal Nocturnal Hemoglobinuria: An Italian Multicenter Survey (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3795;
Vaccines (Comirnaty/Pfizer-BioNTech N=53, mRNA-1273/Moderna N=12, and ChAdOx1 nCov-19/AstraZeneca N=2) were complessively well-tolerated, with 3 non-hematologic adverse events after the first dose (2 fever and 1 exercise-induced tachycardia, grade 1 according to CTCAE v5.0) and 2 after the second one (fever, accompanied by vomit in one patient, grade 1)...BTH has been registered mostly few days after the second dose of vaccine, suggesting a “booster” effect favoring a higher inflammatory response. Watchful clinical and laboratory monitoring is advised, in order to promptly recognize severe hemolytic flares in both treated and naïve patients.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Ultomiris IV (ravulizumab IV) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Evaluation of the Long-Term Safety and Efficacy of Pegcetacoplan Treatment for Paroxysmal Nocturnal Hemoglobinuria Patients: An Extension Study (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3790;
P1, P2a, P
Current C5-inhibitors, such as eculizumab and ravulizumab, are able to partially treat these symptoms by controlling intravascular but not extravascular hemolysis, manifesting as persistent anemia in up to 72% of treated patients and transfusion dependence in up to 36% of patients. Trial results are anticipated in 2022, upon study completion.
- |||||||||| 12-Month Analysis of a Phase 2 Study of Iptacopan (LNP023) Monotherapy for Paroxysmal Nocturnal Hemoglobinuria (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3788;
P2
12-month results from this non-pivotal study demonstrate that iptacopan monotherapy leads to rapid and durable improvements in various hemolytic markers and meaningful and sustained clinical benefit as seen in improvements in Hb levels, transfusion requirement and FACIT fatigue score. These results suggest that proximal inhibition of the complement cascade parallels and further improves the hematological benefit seen with anti-C5 therapies, paving the way for the phase 3 evaluation of iptacopan as potentially new oral first-line therapy for patients with PNH.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Ultomiris IV (ravulizumab IV) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Changes in Hemoglobin Measures Observed in PNH Patients Treated with Both C5 Inhibitors Ravulizumab and Eculizumab: Real-World Evidence from a US-Based EMR Network (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2667;
However, RAV treatment did not markedly alter Hb measures, perhaps due to this being mainly a cohort switching between two therapies with identical mechanisms of action. These RW Hb results suggest that despite C5i treatment, anemia was still largely persistent in this PNH cohort, possibly due to incomplete control of ongoing hemolysis, including extravascular hemolysis, which is not treated by these therapies.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Categorized Hematologic Response to Pegcetacoplan and Correlations with Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria: Post Hoc Analysis of Data from Phase 1b, Phase 2a, and Phase 3 Trials (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2659;
P1, P2a, P
In post hoc analyses of PADDOCK, PALOMINO, and PEGASUS trial data, a substantial proportion of patients achieved and maintained good, major, or complete hematologic responses to PEG, suggesting that PEG can lead to sustained improvements in hematologic parameters. PEGASUS data also demonstrated correlation of improved hematologic response category with clinically meaningful improvements in quality of life, as measured by FACIT-Fatigue.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Journal: Pegcetacoplan versus Eculizumab in PNH. (Pubmed Central) - Nov 4, 2021
This real-world study demonstrated improvement in outcome measures and decreased concomitant drug requirement within 12 months of eculizumab initiation in patients with treatment-refractory AChR+ gMG. No abstract available
- |||||||||| Soliris (eculizumab) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Journal: Pegcetacoplan versus Eculizumab in PNH. (Pubmed Central) - Nov 4, 2021
No abstract available No abstract available
- |||||||||| Soliris (eculizumab) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Journal: Pegcetacoplan versus Eculizumab in PNH. (Pubmed Central) - Nov 4, 2021
No abstract available No abstract available
- |||||||||| Soliris (eculizumab) / AstraZeneca
Paroxysmal Nocturnal Hemoglobinuria in the OR: case report ([VIRTUAL]) - Oct 31, 2021 - Abstract #Euroanaesthesia2021Euroanaesthesia_860;
We believe that the induction of anesthesia associated with the surgical stress and the low platelet count could have triggered this complication. Learning points: Managing surgical stress as a key factor.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Review, Journal: Pregnancy-associated hemolytic uremic syndrome. (Pubmed Central) - Oct 29, 2021
The mainstay of management is supportive care and immediate initiation of plasmapheresis. Eculizumab has been proved to be both safe and effective in inducing and maintaining remission in P-aHUS and it is recommended to be started as soon as the diagnosis is established.
- |||||||||| Soliris (eculizumab) / AstraZeneca
[VIRTUAL] USE OF REMAINING ECULIZUMAB (OVERFILL): COST-OPPORTUNITY ANALYSIS FROM THE PERSPECTIVE OF BENEFITED PATIENTS. WHO CARES? () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1703;
Discussion The effort to avoid unnecessary expenses and maximize benefits within possible resources has been extremely important in Health Economics. Within a public hospital that has scarce resources, the perspective of people who are directly involved with catastrophic situations such as hemolytic/thrombogenic PNH can be the difference between life and death. In this work, an opportunity cost analysis was carried out from the perspective of the benefited patients and the team directly involved (doctors, pharmacists). We see a global savings of BRL 649,382.29 in 42 months. With this amount saved, it was possible to cover shortages or failures in the delivery of medication for seven patients and still save the lives of two patients who needed urgent medication, one of which was at imminent risk of death.
- |||||||||| Soliris (eculizumab) / AstraZeneca
[VIRTUAL] PAROXYSTIC NIGHT HEMOGLOBINURIA ASSOCIATED WITH MYELODYSPLASTIC SYNDROME - CASE REPORT () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1269;
PNH Unlike other erythrocyte abnormalities, PNH is an acquired alteration, expressed in all hematopoietic cells. Resulting from the somatic mutation of the PIG-A gene, which is responsible for the production of Glycosylphofatidyl Inusitol-GPI, an anchor of proteins in the cell membrane such as CD55 and CD59. The partial or total absence of this protein Results in hemolysis mediated by the complement, intravascular system, which is the classic manifestation, which may also present Medullary Failure and Thrombophilia. Despite being a clonal disease, it does not have malignant characteristics, invasion or autonomy. After starting treatment with “Eculizumab”, the patient evolved with an excellent clinical response, with an increase in hemoglobin and becoming independent of transfusion. However, after about 2 years, he developed symptomatic anemia and became transfusion dependent again. At this time, he did not have laboratory markers suggestive of hemolysis or hemoglobinuria. He was then submitted to a Bone Marrow Biopsy, which showed: hypercellularity for age, 75% of cellularity, with a predominance of the erythroid lineage, presenting immature forms and a megaloblastic pattern, with a 1:2 M:E ratio. In addition to small, hypolobulated megakaryocytes. The spinal cord evaluation was compatible with Myelodysplastic Syndrome of the Refractory Anemia Type – MDS-AR. The karyotype study showed: 46 Y, with translocation (X; 5).SMD pathology characterized by clonal hematopoietic alteration, with a variety of clinical presentations and varying degrees of spinal cord insufficiency and peripheral cytopenias. Discussion Diagnosed and treated as PNH, the patient initially responded well to treatment, later evolving with a new exacerbation of anemia. After further investigation, it was concluded to be an SMD. Between 12.3 to 20% of MDS patients have clone HPN. The karyotype alteration presented, translocation (X,5), is noteworthy, with chromosome 5 being commonly involved in MDS and chromosome X, site of the PIG-A gene of PNH.
- |||||||||| Soliris (eculizumab) / AstraZeneca
[VIRTUAL] PAROXYSTIC NIGHT HEMOGLOBINURIA AND APLASTIC ANEMIA - CASE REPORT () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1268;
86% of neutrophils have loss of CD24 and aerolysin expression, in 91% of monocytes have loss of CD14 expression and aerolysin. At the time of treatment, the patient needed transfusion (filtered red blood cells) during the AA. During monitoring, he presented a decrease in platelets associated with asthenia, rectal bleeding, leucopenia, with a need for transfusion to maintain homeostasis. He was treated with cyclosporine for severe aplastic anemia and then Eculizumab was administered in continuous treatment weekly within four weeks (induction phase) followed by a fortnightly period after the fifth week (maintenance phase) in the specific treatment for PNH. Discussion The patient's situation is serious due to the characteristic of the underlying disease, but in response to the treatment, she presented improvements in her clinical condition and quality of life, obtaining improvements in symptomatic anemia and alleviating the condition of abdominal pain and transfusional need, allowing the patient to resume domestic and work activities.Conclusion Early knowledge of the disease (AA) and PNH will benefit the patient in the treatment and improvement of quality of life, minimizing the risk of serious sequelae.
- |||||||||| Soliris (eculizumab) / AstraZeneca
[VIRTUAL] PAROXYSTIC NIGHT HEMOGLOBINURIA (HPN): EXPERIENCE OF THREE TREATMENT CENTERS IN ESPÍRITO SANTO (ES) () - Oct 27, 2021 - Abstract #HEMO2021HEMO_1267;
Objective To describe the epidemiological data of this rare disease in three reference treatment centers in ES .Results In 2021, 7 patients are being followed up, 71% (5) in the university hospital, 28% in other centers. Among these, 1 patient at the State Center for Hemotherapy and 1 at Hospital Santa Casa de Vitória. Most patients are 57% (4) male and 43% (3) female. The mean age at diagnosis was 43 years, with a minimum age of 32 and a maximum of 68 years. Regarding the classification of this disease: 57% (4) have classic PNH and 43% (3) PNH associated with other diagnoses, all of which had a diagnosis of bone marrow aplasia. The average time since diagnosis is 12 years, with a minimum of 6 and a maximum of 22 years. Mean hemoglobin at diagnosis was 8 g/dL. As for complications, 14% (1) had thrombosis, 28% (2) renal failure and 86% (6) required transfusion during follow-up. Most patients have some comorbidity, with a predominance of arterial hypertension 57% (4) and diabetes 28% (2). With regard to treatment, 71% received corticosteroids at some time. A C1 inhibitor (eculizumab) was indicated for all patients, however, 1 (14%) refused treatment and 28% (2) awaits release. 1 patient (14%) required discontinuation of this drug due to an adverse event. Discussion In this cohort, in addition to classic hemolytic anemia, complications such as thrombosis and renal failure were observed. Thrombosis occurs in approximately 40% of patients and transient acute renal failure is associated with hemolytic crises, which may progress to chronic renal failure. In the literature, up to 57% of cases are associated with bone marrow aplasia, a fact also observed in this study. No patient had myelodysplastic syndrome, but this association can be seen in up to 20% of cases. Eculizumab is effective in the treatment, reducing hemolysis, risk of thrombosis and other complications such as pulmonary hypertension, heart failure and kidney failure. As noted, adherence to intravenous treatment and potential adverse events of this drug are challenges in daily clinical practice.Conclusion PNH is a rare disease, and follow-up at referral centers is recommended. It is necessary to be aware of its association with bone marrow failures and complications of chronic hemolysis. Management can be challenging considering the difficulties in accessing medication, the lack of therapeutic options that provide better adherence, and the failure to respond or adverse events to first-line C1 inhibitors.
- |||||||||| Soliris (eculizumab) / AstraZeneca
[VIRTUAL] ANALYSIS OF BASELINE CHARACTERISTICS, DISEASE BURDEN AND LONG-TERM FOLLOW-UP OF 167 PATIENTS WITH BRAZILIAN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA - ANOTHER NATURAL HISTORY () - Oct 27, 2021 - Abstract #HEMO2021HEMO_82;
The average follow-up period was 74 months (1 - 330 months), with 31 deaths in total (80.4% OS). Sepsis was the leading cause of sc-PNH mortality (16/18, 88.8%), and thrombosis in both hemolytic groups (11/13, 84.6%). Log rank test shows similar survival when comparing patients with diagnosis until and after 2007 (p = 0.04). Conclusion this study suggests clonal evolution in the long-term follow-up of aplastic patients and confirms the observation that high levels of PNH and LDH clones are associated with life-threatening hemolysis and thrombosis, while small PNH clones and young age are associated with the subclinical form of the disease. Although without statistical significance, the cumulative incidence of thrombosis in the group after 2008 appears to be lower than the previous period, perhaps due to the routine use of Eculizumab.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Clinical, Journal: C3 glomerulopathy: experience of a pediatric nephrology center. (Pubmed Central) - Oct 27, 2021
C3G shows a variable clinical presentation and response to immunosuppressive therapy. In the present study, we observed that the most common presentation was nephritic and/or nephrotic syndrome and partially responded to treatment to RASB and immunosuppressants.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Ultomiris IV (ravulizumab IV) / AstraZeneca
Review, Journal: Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. (Pubmed Central) - Oct 27, 2021
The most common treatment-related adverse events with ravulizumab in treatment-naïve patients include headache, diarrhoea and vomiting. With its convenient once every 4-8 weeks maintenance regimen, ravulizumab is an important treatment option for aHUS in adult and paediatric patients.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Clinical, Journal: Utilization Pattern for Eculizumab Among Children With Hemolytic Uremic Syndrome. (Pubmed Central) - Oct 25, 2021
Children who presented with neurological and cardiac involvement with severe disease were more likely to receive eculizumab therapy, and children who received therapy received it early during their index hospitalization. Further prospective studies are suggested to confirm these findings.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Clinical, Journal: Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series. (Pubmed Central) - Oct 25, 2021
(4) In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Review, Journal: Planned Pregnancy in Kidney Transplantation. A Calculated Risk. (Pubmed Central) - Oct 25, 2021
Rituximab and eculizumab should be used in pregnancy only if the benefits outweigh the risk for the fetus. Renin-angiotensin system inhibitors, mycophenolate, bortezomib, and cyclophosphamide can lead to fetal toxicity and should not be prescribed to pregnant women.
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, Soliris (eculizumab) / AstraZeneca
Review, Journal: Treatment and new evidences in neuromyelitis optica spectrum disorder (Pubmed Central) - Oct 22, 2021
This article discusses off-label azathioprine and mycophenolate mofetil in the treatment of NMOSD and reviews the evidence-based clinical aspects of B/plasma cell depletion, antagonization of IL-6 signaling and blocking the complement pathway...In the recent two years, phase 3 clinical trials provided class I evidence for the efficacy and safety of rituximab (anti-CD20), inebilizumab (anti-CD19), tocilizumab (anti-IL6R), satralizumab (anti-IL6R), and eculizumab (anti-C5) in combination with other immunosuppressants or in monotherapy...Immunosuppression is recommended in NMOSD during pregnancy and lactation, and this should be considered for optimal selection of treatment in fertile female patients. The new monoclonal antibodies broadened treatment options NMOSD, and the treatment strategy of MOGAD has become more straightforward.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Journal: De novo thombotic microangiopathy (TMA) after incompatible AB0 renal transplantation (Pubmed Central) - Oct 22, 2021
The new monoclonal antibodies broadened treatment options NMOSD, and the treatment strategy of MOGAD has become more straightforward. It has to be discussed whether an early use of eculizumab in cases of suspected de novo TMA is a safe way to prevent graft dysfunction and thus to improve the poor prognosis for graft and recipient described in the literature.
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