INTRODUCTION: The remarkable ability of human pluripotent stem cells (hPSCs) to differentiate into specialized cells of the human body emphasizes their immense potential in treating various diseases. Advances in hPSC tec...INTRODUCTION: The remarkable ability of human pluripotent stem cells (hPSCs) to differentiate into specialized cells of the human body emphasizes their immense potential in treating various diseases. Advances in hPSC technology are paving the way for personalized and allogeneic cell-based therapies. The first-in-human studies showed improved treatment of diseases with no adverse effects, which encouraged the industrial production of this type of medicine. To ensure the quality, safety and efficacy of hPSC-based products throughout their life cycle, it is important to monitor and control their clinical translation through good practices (GxP) regulations. Understanding these rules in advance will help ensure that the industrial development of hPSC-derived products for widespread clinical implementation is feasible and progresses rapidly. AREAS COVERED: In this review, we discuss the key translational obstacles of hPSCs, outline the current hPSC-based clinical trials, and present a workflow for putative clinical hPSC-based products. Finally, we highlight some future therapeutic opportunities for hPSC-derivatives. EXPERT OPINION: hPSC-based products continue to show promise for the treatment of a variety of diseases. While clinical trials support the relative safety and efficacy of hPSC-based products, further investigation is required to explore the clinical challenges and achieve exclusive regulations for hPSC-based cell therapies.
INTRODUCTION: CHAPLE disease is a severe, ultra-rare disorder caused by CD55 gene mutations, leading to uncontrolled complement hyperactivation, protein-losing enteropathy, and systemic thrombosis. Recent advances in tar...INTRODUCTION: CHAPLE disease is a severe, ultra-rare disorder caused by CD55 gene mutations, leading to uncontrolled complement hyperactivation, protein-losing enteropathy, and systemic thrombosis. Recent advances in targeted therapies, particularly the C5 inhibitor pozelimab (Veopoz), offer new treatment options by addressing complement dysregulation, marking a shift from symptomatic to precision therapy. AREAS COVERED: This review explores the pathophysiology, clinical manifestations, and current treatments for CHAPLE disease. It examines pozelimab's pharmacological development, its mechanism as a C5 inhibitor, and results from Phase 1 to Phase 3 studies. Additionally, potential use of other anti-C5 therapies and emerging agents targeting proximal complement components are discussed. A systematic literature search using PubMed, Google Scholar, and ClinicalTrials.gov focused on studies from 2017 onwards to provide a comprehensive overview. EXPERT OPINION: Managing CHAPLE disease requires a combination of targeted anti-complement therapies like pozelimab and supportive measures, including nutritional support and thrombosis management. While pozelimab shows promise in reversing core symptoms, risks like serious infections necessitate preventive measures, such as vaccination and antibiotic prophylaxis. Future research should focus on optimizing dosing, evaluating long-term safety, and assessing the need for lifelong therapy. Expanding our understanding of the disease's pathophysiology will refine treatment strategies and improve outcomes.
INTRODUCTION: Emerging evidence suggests that, while CD19 is primarily expressed on immature B-cell precursors, it is also present on drug-resistant plasma cells that have been postulated to function as multiple myeloma...INTRODUCTION: Emerging evidence suggests that, while CD19 is primarily expressed on immature B-cell precursors, it is also present on drug-resistant plasma cells that have been postulated to function as multiple myeloma (MM) stem cells, driving the progression of relapsing disease. Targeting CD19 with chimeric antigen receptor (CAR) T cells offers a promising strategy for addressing this residual disease burden, potentially leading to more durable treatments and enhanced relapse prevention. AREAS COVERED: This review examines the molecular basis of CD19-targeted CAR-T therapy in MM, highlighting its potential, key challenges, and efficacy and safety in early clinical trials for relapsed/refractory and newly diagnosed MM. EXPERT OPINION: CD19 expression in MM correlates with poor prognosis and may be significantly underestimated, particularly following debulking therapy, as demonstrated by advanced visualization technologies like single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM). Early-phase trials using CD19-directed CAR-T as post-transplant consolidation show promise in prolonging progression-free survival. Multi-target approaches, e.g. the bispecific BCMA×CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data. However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape.
INTRODUCTION: Hypercholesterolemia and other lipid disorders are major causes of atherosclerotic cardiovascular disease (ASCVD). Statins have been the mainstay of lipid-lowering therapy for many years, but they may not b...INTRODUCTION: Hypercholesterolemia and other lipid disorders are major causes of atherosclerotic cardiovascular disease (ASCVD). Statins have been the mainstay of lipid-lowering therapy for many years, but they may not be adequate to achieve the target low-density lipoprotein (LDL) cholesterol levels and there are other residual lipid risk factors. AREAS COVERED: This article reviews the biologic therapies in development for hypercholesterolemia identified by a PubMed search. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a major focus, but the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3) that were originally developed to reduce the levels of triglyceride-rich lipoproteins are now being explored to reduce cardiovascular events in a wider range of patients. A brief overview of biologic therapies targeting lipoprotein(a) [Lp(a)] is also proved. EXPERT OPINION: Inhibition of PCSK9 remains an attractive target. In addition to the currently available monoclonal antibodies (mAbs) and small interfering RNA (siRNA), new mAbs and the adenectin lerodalcibep are promising therapies. The antisense oligonucleotide (ASO) and siRNA inhibitors of apoC3 and ANGPTL3 are effective in severe hypertriglyceridemia and homozygous familial hypercholesterolemia, respectively, and may prove to have wider applications. ASO and siRNA inhibitors of Lp(a) are currently in cardiovascular outcome studies.
Lopes S, Servadio M, Spini A
… +23 more, L'Abbate L, Ingrasciotta Y, Giometto S, Lucenteforte E, Leoni O, Zanforlini M, Ancona D, Stella P, Puccini A, Sapigni E, Rossi P, Ejlli L, Balducci F, Mangano AMP, Ledda S, Carta P, Scarpelli RF, De Sarro G, Massari M, Spila Alegiani S, Addis A, Trifirò G, Belleudi V
BACKGROUND: Monitoring biologic drug therapy during pregnancy in women with immune-mediated inflammatory diseases (IMIDs) is crucial to ensure treatments align with evidence-based practices. RESEARCH DESIGN AND METHODS:...BACKGROUND: Monitoring biologic drug therapy during pregnancy in women with immune-mediated inflammatory diseases (IMIDs) is crucial to ensure treatments align with evidence-based practices. RESEARCH DESIGN AND METHODS: A retrospective cohort study based on healthcare claims data from eight Italian regions was conducted, analyzing deliveries between 2009 and 2021. The study included women receiving biologic drugs within nine months before their last menstruation. Exposures to biologics, conventional disease-modifying anti-rheumatic drugs (DMARDs) and symptom-relieving medications were assessed in the trimesters (T) before, during and after pregnancy. Factors influencing biologic treatment persistence during pregnancy were analyzed. RESULTS: A cohort of 1,763 deliveries was considered. Biologic drugs were prescribed for rheumatic (33.6%), dermatological (32.6%), and gastrointestinal diseases (28.4%). Biologic use declined during pregnancy (TI = 37.3%; TII = 17.6%; TIII = 11.3%), increasing again postpartum. During pregnancy, there was increased use of symptom-relieving medications for rheumatic diseases and DMARDs for gastrointestinal diseases. Factors associated with continued biologic treatment included being older than 35 years and the region of delivery. CONCLUSIONS: This study found a decrease in biologics drug use during pregnancy and highlights the necessity for personalized therapeutic approaches. Geographic variations in biologic drug use emphasize the need for educational initiatives about the risk-benefit profiles of these therapies during pregnancy.
INTRODUCTION: Revolutionary drugs have been developed and approved in the last 5 years for the treatment of hereditary angioedema (HAE). Increased knowledge of HAE pathophysiology has led to the development of innovative...INTRODUCTION: Revolutionary drugs have been developed and approved in the last 5 years for the treatment of hereditary angioedema (HAE). Increased knowledge of HAE pathophysiology has led to the development of innovative drugs for self-administered on-demand therapy and for short- and long-term prophylaxis (LTP). This has rendered possible a personalized approach for patients, allowing greater control of symptoms, better quality of life and reduction in the incidence of adverse effects linked to old treatments. AREAS COVERED: In this review we have highlighted which treatments are currently approved for HAE and some of the promising future therapies under development. EXPERT OPINION: While the first generation of approved treatments improved disease control for most patients, innovative therapies may allow individualized action plans and reduce complexity of treatment. Switching therapies due to insufficient efficacy, patient preference or adverse events is becoming progressively feasible and common. New LTPs may lead to the achievement of attack-free remission, allowing us to hopefully reach complete disease control for all patients and further improving their quality of life. In particular, LTPs with longer administration intervals, and on-demand therapies administered via the oral route will have a key role and will set more prominent targets for the upcoming drugs.
INTRODUCTION: Engineering of the drug half-life in vivo has become an integral part of modern biopharmaceutical development due to the fact that many proteins/peptides with therapeutic potential are quickly cleared by ki...INTRODUCTION: Engineering of the drug half-life in vivo has become an integral part of modern biopharmaceutical development due to the fact that many proteins/peptides with therapeutic potential are quickly cleared by kidney filtration after injection and, thus, circulate only a few hours in humans (or just minutes in mice). AREAS COVERED: Looking at the growing list of clinically approved biologics that have been modified for prolonged activity, and also the plethora of such drugs under preclinical and clinical development, it is evident that not one solution fits all needs, owing to the vastly different structural features and functional properties of the pharmacologically active entities. This article provides an overview of established half-life extension strategies, as well as of emerging novel concepts for extending the in vivo stability of biologicals, and their pros and cons. EXPERT OPINION: Beyond the classical and still dominating technologies for improving drug pharmacokinetics and bioavailability, Fc fusion and PEGylation, various innovative approaches that offer advantages in different respects have entered the clinical stage. While the Fc fusion partner may be gradually superseded by engineered albumin-binding domains, chemical PEGylation may be replaced by biodegradable recombinant amino-acid polymers like PASylation, thus also offering a purely biotechnological manufacturing route.
INTRODUCTION: Modern anti-myeloma therapies have broken new ground in the treatment of the disease, and the incorporation of ide-cel in the treatment landscape represents one of the major scientific and clinical advances...INTRODUCTION: Modern anti-myeloma therapies have broken new ground in the treatment of the disease, and the incorporation of ide-cel in the treatment landscape represents one of the major scientific and clinical advances. AREAS COVERED: Ide-cel was the first cell-based gene therapy approved for the treatment of triple-class exposed relapsed/refractory myeloma patients, showing impressive results, and demonstrating superiority over standard regimens in terms of efficacy, potential treatment-free intervals, and improved quality of life in heavily pretreated patients and in high-risk disease. This review summarizes the state-of-the-art of the most recent updates deriving from the use of ide-cel within ongoing, or upcoming, clinical trials, and from real-life experiences. EXPERT OPINION: As the use of chimeric antigen receptor (CAR)-T therapy is likely to progressively increase over time and current indications expand to earlier treatment lines, efforts should be directed toward ameliorating overall management to facilitate proactive planning for treatment sequencing and provide adequate time for logistical planning. Importantly, the potential limited availability of CAR-T therapy highlights the importance of careful patient selection and coordination among centers. Meanwhile, attempts are underway to improve tolerance and reduce toxicity while enhancing anti-myeloma activity.
INTRODUCTION: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Moderate-to-severe AD severely affects patients' quality of life. New drugs selectively targeting molecular pathways involved in the pat...INTRODUCTION: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Moderate-to-severe AD severely affects patients' quality of life. New drugs selectively targeting molecular pathways involved in the pathogenesis of the disease led to a new era for the treatment of AD. However, the current available options are limited and do not completely fulfill patients' needs. Recently, lebrikizumab, a new humanized monoclonal antibody targeting IL-13, has been approved for treating moderate-to-severe AD. AREAS COVERED: By analyzing scientific literature reporting lebrikizumab phase 3 pivotal clinical studies and summarizing recent advances in AD pathogenesis, in this article we focused on the mechanism of action of lebrikizumab in comparison to other biologics used for treating AD and discussed clinical data that led to the approval of this biologic agent. EXPERT OPINION: Among biologics approved for moderate-to-severe AD, lebrikizumab is characterized by a unique mechanism of action and an attractive maintenance regimen, besides good efficacy and safety profiles. Moreover, clinical evidence suggests that patients naïve or pre-treated with other biologics and affected by AD localized in sensitive areas and by type 2 comorbidities might be successfully treated with lebrikizumab.
INTRODUCTION: Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to i...INTRODUCTION: Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to identify patient groups which are most likely to benefit from such therapeutic approaches. AREAS COVERED: In the current article, we will provide an overview of recent results and ongoing and future research directions of immunotherapy in BTC, with a special focus on recently published, practice-changing data, and ongoing active and recruiting clinical trials. EXPERT OPINION: At this moment, dozens of clinical trials in phases I to III are evaluating the role of cancer immunotherapy in this setting, with the hope of adding more therapeutic options for BTC patients. Future research must focus on the development of novel agents and combinations, but the validation of biomarkers remains an urgent need. As more research results emerge, novel combinatorial strategies are destined to further transform the treatment paradigm for this heterogeneous and aggressive tumor type.
BACKGROUND: To support an interchangeability designation for Sandoz adalimumab biosimilar (GP2017), antidrug antibody (ADA) signal-to-noise (S/N) ratios were assessed in the GP2017 ADACCESS trial to directly assess poten...BACKGROUND: To support an interchangeability designation for Sandoz adalimumab biosimilar (GP2017), antidrug antibody (ADA) signal-to-noise (S/N) ratios were assessed in the GP2017 ADACCESS trial to directly assess potential changes in immunogenicity. RESEARCH DESIGN AND METHODS: ADACCESS was a 51-week trial in patients with moderate-to-severe plaque psoriasis that included patients treated continuously with reference adalimumab (cH), and patients who experienced four switches between reference adalimumab and GP2017 (H2H). ADAs were measured every 6 weeks during the switching phase using an electrochemiluminescence assay. A non-parametric analysis was performed to estimate the 90% confidence interval (CI) of the median of difference in ADA S/N ratios between the cH and H2H treatment groups at week 41. If the 90% CI was within the margin of -0.16 to 0.16 (representing assay noise), this was considered a non-clinically meaningful difference in immunogenicity. RESULTS: The 90% CIs of the median of difference in ADA S/N ratios between the two treatment groups were within the defined margin of -0.16 to 0.16 at week 41, and at all other time points. Efficacy and safety data were also similar between the treatment groups. CONCLUSION: Analysis of ADA S/N ratios showed no increase in immunogenicity following up to four switches between reference adalimumab and GP2017. TRIAL REGISTRATION: NCT02016105.
INTRODUCTION: Standardized evaluation of endoscopic disease activity using valid, responsive and reliable instruments is crucial for optimizing the efficiency of clinical trials with therapeutic agents for Crohn's diseas...INTRODUCTION: Standardized evaluation of endoscopic disease activity using valid, responsive and reliable instruments is crucial for optimizing the efficiency of clinical trials with therapeutic agents for Crohn's disease (CD). Achieving endoscopic remission and/or mucosal healing is associated with improved long-term outcomes, making it an important treatment goal. AREAS COVERED: Several endoscopic indices have been used over the past two decades, though they lack complete validation. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Score for Crohn's Disease (SES-CD) demonstrate fair reliability and responsiveness to treatment. The CDEIS is rather complex and time-consuming, and both endoscopic indices are prone to variability. The Lewis Score and Capsule Endoscopy CD Activity Index (CECDAI) provide useful alternative instruments using video capsule endoscopy, but they need further validation. The Rutgeerts score predicts post-surgical recurrence but lacks evaluation for follow-up. EXPERT OPINION: While recent guidelines emphasize co-primary clinical and endoscopic endpoints to improve trial effectiveness, these are typically based on expert consensus rather than empirical data. We advocate to use SES-CD as the preferred endoscopic index given its simplicity, strong correlation with CDEIS, and treatment responsiveness. Future research should focus on establishing clinically relevant cutoff values for endoscopic response and endoscopic remission in CD trials, including post-operative settings.
INTRODUCTION: Risankizumab (RZB) is a recombinant IgG humanized monoclonal antibody which selectively inhibits interleukin (IL)-23 though high-affinity binding of the p19 subunit. RZB was approved for use in Crohn's dise...INTRODUCTION: Risankizumab (RZB) is a recombinant IgG humanized monoclonal antibody which selectively inhibits interleukin (IL)-23 though high-affinity binding of the p19 subunit. RZB was approved for use in Crohn's disease (CD) in 2022 and received regulatory approval for ulcerative colitis (UC) in the United States in June 2024. AREAS COVERED: We will examine currently available therapies for UC, provide an overview of the IL-23 pathway, discuss available trial data for RZB in UC, and comment on how RZB may fit into the current UC treatment paradigm and future directions in the field. EXPERT OPINION: RZB appears to be an effective agent for inducing and maintaining remission in patients with both treatment-naïve and refractory UC, with a favorable safety profile. The selective blockade of IL-23 has demonstrated potential advantages in efficacy over combined IL-12/23 inhibition for other disease states like CD and psoriasis, although where it will be positioned amidst other clinically available advanced therapies in UC requires further study.
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy and have enhanced the survival of patients with malignant tumors. However, the overall efficacy of ICIs remains unsa...INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy and have enhanced the survival of patients with malignant tumors. However, the overall efficacy of ICIs remains unsatisfactory and is faced with two major concerns of resistance development and occurrence of immune-related adverse events (irAEs). Bispecific antibodies (bsAbs) have emerged as promising strategies with unique mechanisms of action to achieve a better efficacy and safety than monoclonal antibodies (mAbs) or even their combination. BsAbs along with other bispecific platforms such as bispecific fusion proteins, nanobodies, and CAR-T cells may help to avoid development of resistance and reduce irAEs caused by on-target/off-tumor binding effects of mAbs. AREAS COVERED: A literature search was performed using PubMed for English-language articles to provide a comprehensive overview of preclinical and clinical studies on bsAbs specified for both immune checkpoints and non-checkpoint molecules as a well-enhanced class of therapeutics. EXPERT OPINION: Identifying suitable targets and selecting effective engineering platforms enhance the potential of bsAbs to address the challenges associated with conventional therapies such as ICIs, positioning them as a promising class of therapeutics in the landscape of cancer immunotherapy.
OBJECTIVES: This analysis reported the incidence of safety endpoints across five phase 3 randomized controlled clinical trials in patients with rheumatoid arthritis (RA), Crohn's disease (CD), and chronic plaque psoriasi...OBJECTIVES: This analysis reported the incidence of safety endpoints across five phase 3 randomized controlled clinical trials in patients with rheumatoid arthritis (RA), Crohn's disease (CD), and chronic plaque psoriasis (PsO) who received ≥ 1 dose of adalimumab-adbm or adalimumab reference product (RP). METHODS: Exposure-adjusted incidence rates for safety endpoints were calculated per 100 patient-years and reported by disease indication and treatment arm. Subgroup analyses by patient age and sex were also conducted. RESULTS: The mean length of follow-up was 62 weeks, 48 weeks, and 32 weeks for patients with RA, CD, and PsO, respectively. Rates of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) were similar among patients with RA and PsO, but slightly higher among those with CD. Incidence rates of all safety endpoints were consistent between the adalimumab-adbm and adalimumab RP treatment arms within each indication Subgroup analyses of patients with RA, CD, and PsO showed no between-group differences by age and sex. CONCLUSIONS: In patients with RA, CD, and PsO, there were no differences between biosimilar adalimumab-adbm or the adalimumab RP regarding the rate of AEs, SAEs, discontinuations due to AEs, deaths, or any AEs of special interest.
INTRODUCTION: Less than half of the subjects with hypertension have been diagnosed and treated, with only 21% having their blood pressure under control. Many of the subjects find it difficult to adhere to daily antihyper...INTRODUCTION: Less than half of the subjects with hypertension have been diagnosed and treated, with only 21% having their blood pressure under control. Many of the subjects find it difficult to adhere to daily antihypertensives. Zilebesiran reduces hepatic angiotensinogen messenger RNA levels to inhibit the renin-angiotensin-aldosterone system and is being developed as a long-acting anti-hypertensive agent. AREAS COVERED: KARDIA-1; a phase 2 clinical trial of zilebesiran with mild-to-moderate hypertension. Most doses of zilebesiran (150-600 mg) modestly reduced blood pressure from baseline to month 3. Adverse events included hyperkalemia and kidney failure. EXPERT OPINION: The main problem with zilebesiran is that it only has a modest effect on blood pressure, and it is likely to have to be used as add-on therapy, which will probably reduce any benefits on adherence it has. It was also difficult to reliably interpret the results of KARDIA-1 as blood pressure went up significantly in the placebo group. KARDIA-1 did not answer previous concerns about zilebesiran; (i) what happens during volume depletion, sepsis, and pregnancy when angiotensinogen is inhibited long term or (ii) will it be effective in a high sodium diet.
INTRODUCTION: Systemic treatment options for renal cell carcinoma (RCC) have expanded considerably in recent years, and both tyrosine kinase inhibitors and immune checkpoint inhibitors, alone or in combination, have ente...INTRODUCTION: Systemic treatment options for renal cell carcinoma (RCC) have expanded considerably in recent years, and both tyrosine kinase inhibitors and immune checkpoint inhibitors, alone or in combination, have entered the clinical arena. Adoptive cell immunotherapies have recently revolutionized the treatment of cancer and hold the promise to further advance the treatment of RCC. AREAS COVERED: In this review, we summarize the latest preclinical and clinical development in the field of adoptive cell immunotherapy for the treatment of RCC, focusing on lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, tumor-infiltrating T cells (TILs), TCR-engineered T cells, chimeric antigen receptor (CAR) T cells, and dendritic cell vaccination strategies. Perspectives on emerging cellular products including CAR NK cells, CAR macrophages, as well as γδ T cells are also included. EXPERT OPINION: So far, areas of greater therapeutic success of adoptive cell therapies include the adjuvant administration of CIK cells and the transfer of anti-CD70 CAR T cells in patients with metastatic RCC. Bench to bedside and back research will be needed to overcome current limitations of adoptive cell therapies in RCC, primarily aiming at improving the safety of immune cell products, optimizing their antitumor activity and generating off-the-shelf products ready for clinical use.
INTRODUCTION: Locally advanced esophageal cancer (EC) has poor prognosis. Preliminary clinical studies have demonstrated the synergistic efficacy of radiotherapy combined with immunotherapy in EC. Adjusting the radiother...INTRODUCTION: Locally advanced esophageal cancer (EC) has poor prognosis. Preliminary clinical studies have demonstrated the synergistic efficacy of radiotherapy combined with immunotherapy in EC. Adjusting the radiotherapy target volume to protect immune function favors immunotherapy. However, there is no clear consensus on the exact definition of the EC target volume. AREAS COVERED: Preclinical studies have provided a wealth of information on immunotherapy combined with different radiotherapy modalities, and several clinical studies have evaluated the impact of immunotherapy combined with radiotherapy on locally advanced EC. Here, we illustrate the rational target volume delineation for radiotherapy in terms of patient prognosis, pattern of radiotherapy failure, treatment-related toxicities, tumor-draining lymph nodes, and systemic immunity and summarize the clinical trials of radiotherapy combined with immunotherapy in EC. EXPERT OPINION: We recommend applying involved-field irradiation (IFI) instead of elective nodal irradiation (ENI) for irradiated fields when immunotherapy is combined with chemoradiotherapy (CRT) for locally advanced EC. We expect that this target design will be evaluated in clinical trials to further explore more precise diagnostic modalities, long-term toxic responses, and quality of survival, and stratification factors for personalized treatment, and to provide more treatment benefits for patients.
INTRODUCTION: Following the CHAMPION-NMOSD trial, the FDA recently granted approval for ravulizumab, a humanized monoclonal antibody against complement C5 protein in AQP-4 seropositive neuromyelitis optica spectrum disor...INTRODUCTION: Following the CHAMPION-NMOSD trial, the FDA recently granted approval for ravulizumab, a humanized monoclonal antibody against complement C5 protein in AQP-4 seropositive neuromyelitis optica spectrum disorder (NMOSD). Similar to eculizumab, ravulizumab offers near-complete prevention of NMOSD relapses, but has a longer half-life, providing decreased infusion frequency and increased convenience for patients. While targeting the complement pathway has clear advantages, patients are at risk for infection with encapsulated organisms, in particular . AREAS COVERED: In this paper, we discuss the details of the CHAMPION-NMOSD trial and discuss challenges in meningitis prevention and strategies for switching therapies. EXPERT OPINION: Ravulizumab improves on eculizumab's success as a highly effective NMOSD therapy by decreasing infusion frequency, thereby increasing patient convenience. We predict that ravulizumab will eventually replace eculizumab but may not have a similar impact on inebelizumab or satralizumab. Patients taking C5 complement inhibitors have an increased risk of serious meningococcal infections, such as invasive meningococcal disease (IMD), and have incomplete protection against IMD despite immunization. Thus, we recommend that in addition to standard pre-immunizations against , patients should also be assessed for starting on appropriate antibiotic prophylaxis against IMD, based on local resistance patterns.