Additional effect of erenumab for patients with chronic migraine treated with onabotulinumtoxin A—real-world data from a preliminary cohort study

BackgroundThis preliminary retrospective cohort study investigates the potential additive prophylactic effect of erenumab, a fully human monoclonal antibody that blocks the calcitonin gene-related peptide receptor, in combination with ongoing onabotulinumtoxin A (onaBoNT-A) treatment in patients suffering from chronic migraine.MethodsThe study included 218 patients and investigated the effects of adding erenumab to the existing treatment regimen. The primary outcome was the MIDAS (Migraine Disability Assessment) score assessed 3 months after the introduction of erenumab.ResultsThe results indicated a significant improvement of the MIDAS score, suggesting a reduction in migraine-related disability following the addition of erenumab to onaBoNT-A. In the inter group comparison, dual therapy showed a significantly greater reduction of the MIDAS when compared to a switch from onaBoNT-A to erenumab monotherapy, but not compared to initiation of onaBoNT-A monotherapy. It is hypothesized that the observed additive effects are due to the independent modes of action of erenumab and onabotulinumtoxin A.ConclusionThis study suggests that the combination of erenumab with onaBoNT-A may offer an improved approach for the treatment of chronic migraine in selected patients. However, the results highlight the need for prospective, controlled studies to validate these findings and determine the optimal combination of treatments tailored to the individual patient

Pdgf Ve Bmp-6’nin Ardişik Salimi Sonrasi Mc3t3-E1osteoblast Hücrelerinin Proliferasyonu. In Vitro Birçalişma

Background and Aim: To evaluate the release kinetics of bone morphogenetic protein (BMP)-6 or -7 loaded nanoparticles (NPs) that located inside the microparticles (MPs) carrying platelet-derived growth factor (PDGF), and test this NP-in-MP system with MC3T3-E1 osteoblastic cells. Materials and Methods: Poly-lactic acid-co-glycolic acid (PLGA) NPs was loaded with BMP-6 or -7 and inserted in sodium alginate MPs loaded with PDGF. To evaluate the osteoblastic effect; proliferation of MC3T3-E1 cells that were treated with BMP-6, -7 and PDGF free solutions (FS) or within the particles (BMP-6 or -7 loaded PLGA NP alone and BMP-6 or -7 loaded PLGA NP in PDGF loaded alginate MP) were assessed at 2, 4, 7, 14 and 21 days. Results: It was shown that while both NP and NP-in-MP systems showed similar burst release at first time periods; especially in 24-72 h time period, NP-in-MP system exhibited a sustained release profile till 14th day. According to proliferation experiments, till the 7th day, both particle and FS groups exhibited similar profiles, but after that time particle groups, especially BMP-7 NP in PDGF MP, reached to statistically higher cell numbers than FS groups. NP-in-MP system exhibited a gradually longer time factor release resulting with delayed but elongated cell proliferation period. Conclusion: Findings indicate that NP-in-MP system might be promising in future for mimicking the natural bone formation process by providing sequential release of PDGF and BMPs, for bone tissue engineering. More comprehensive experiments evaluating mineralization and gene expression profile is necessary to verify these resultsAmaç: Mevcut çalışma trombosit kaynaklı büyüme faktörü (platelet-derived growth factor, PDGF) taşıyan mikropartiküller (MP) içerisine hapsedilmiş nanopartiküller (NP)'den kemik morfogenetik protein (bone morphogenetic protein, BMP)6 veya -7'nin salım kinetiğini değerlendirmek ve bu sistemi MC3T3-E1 osteoblastik hücreleri ile test etmektir. Gereç ve Yöntemler: Polilaktik asit-glikolik asit (PLGA) NP'ler BMP-6 veya BMP-7 ile yüklenmiş ve PDGF ile doldurulmuş sodyum aljinat MP'lere yerleştirilmiştir. Osteoblastik etkiyi değerlendirmek için serbest veya partiküller içerisinde yüklü (BMP-6 veya BMP-7 yüklenmiş PLGA NP ile PDGF yüklenmiş aljinat MP içerisinde BMP-6 veya BMP-7 yüklenmiş PLGA NP) BMP-6, -7 ve PDGF ile muamele edilip 2, 4, 7, 14 ve 21. günlerde incelenmiştir. Bulgular: İlk zaman periyotlarında hem NP hem de MP içerisinde NP sistemleri benzer patlayıcı salım miktarı gösterirken özellikle 24-72 saat zaman diliminde MP içerisinde NP sistemi 14. güne kadar uzamış bir salım profili ortaya koymuştur. Proliferasyon deneylerine göre 7. Güne kadar her iki partikül grubu ve serbest solüsyon grupları benzer profiller oluşturmuştur ancak bu periyottan sonra özellikle PDGF MP içerisinde BMP-7 NP grubu olmak üzere partikül grupları, FS gruplarına kıyasla istatistiksel olarak anlamlı düzeyde daha fazla hücre sayısına ulaşmıştır. MP içinde NP sistemi ise dereceli ve daha uzun süren bir faktör salımı yaparak gecikmiş ve uzamış bir yüksek hücre proliferasyon periyodu sağlamıştır. Sonuç: Mevcut deneylerin bulguları MP içinde NP sisteminin PDGF and BMP'lerin ardışık salımını sağlayarak gelecekte kemik doku mühendisliğinde doğal kemik formasyon sürecini taklit edebileceği konusunda ümit vermektedir. Ancak bu sonuçları doğrulamak için mineralizasyon ve gen ekspresyon profillerini içeren daha kapsamlı deneylere ihtiyaç vardı

Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients

Background: Myasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome. Methods: We examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation. Results: 815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and antimuscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange. Conclusions: MC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients

Eculizumab versus rituximab in generalised myasthenia gravis

Objective Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction. However, evidence shaping treatment decisions, particularly for treatment-refractory cases, is sparse. Both rituximab and eculizumab may be considered as therapeutic options for refractory MG after insufficient symptom control by standard immunosuppressive therapies. Methods In this retrospective observational study, we included 57 rituximab-treated and 20 eculizumab-treated patients with MG to compare the efficacy of treatment agents in generalised, therapy-refractory anti-acetylcholine receptor antibody (anti-AChR-ab)-mediated MG with an observation period of 24 months. Change in the quantitative myasthenia gravis (QMG) score was defined as the primary outcome parameter. Differences between groups were determined in an optimal full propensity score matching model. Results Both groups were comparable in terms of clinical and demographic characteristics. Eculizumab was associated with a better outcome compared with rituximab, as measured by the change of the QMG score at 12 and 24 months of treatment. Minimal manifestation of disease was more frequently achieved in eculizumab-treated patients than rituximab-treated patients at 12 and 24 months after baseline. However, the risk of myasthenic crisis (MC) was not ameliorated in either group. Interpretation This retrospective, observational study provides the first real-world evidence supporting the use of eculizumab for the treatment of refractory, anti-AChR-ab positive MG. Nonetheless, the risk of MC remained high and prompts the need for intensified monitoring and further research effort aimed at this vulnerable patient cohort