BACKGROUND: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents.
METHODS: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab).
RESULTS: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001).
CONCLUSIONS: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.

UNASSIGNED: The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
UNASSIGNED: PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger\'s test.
UNASSIGNED: The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves\' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
UNASSIGNED: The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
UNASSIGNED: inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.

UNASSIGNED: The purpose of this study was to evaluate the risk of secondary immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab through a meta-analysis.
UNASSIGNED: We searched databases including PubMed, Web of Science, OVID and EMBASE for studies reporting changes in platelet levels in MS patients treated with alemtuzumab from their inception until May 2023 and performed a meta-analysis. Information and data were screened and extracted by two researchers. The inclusion and exclusion criteria were established according to the PICOS principle. The obtained data were analyzed using the R software meta package and the quality assessment was conducted using Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger test.
UNASSIGNED: A total of 15 studies were included, encompassing 1,729 multiple sclerosis patients. Meta-analysis of overall secondary ITP in the included studies yielded a pooled rate of 0.0243. The overall incidence of secondary autoimmune events was 0.2589. In addition, subgroup analysis was applied using study regions and study types. The results showed that the incidence rate of secondary ITP in Europe was about 0.0207, while the incidence of autoimmune events (AEs) was 0.2158. The incidence rate of secondary ITP and AEs in North America was significantly higher than in Europe, being 0.0352 and 0.2622. And the analysis showed that the incidence rates of secondary ITP and AEs in prospective studies were 0.0391 and 0.1771. Retrospective studies had an incidence rate of secondary ITP at 2.16, and an incidence rate of AEs at 0.2743.
UNASSIGNED: This study found that there was a certain incidence of Immune thrombocytopenia in multiple sclerosis patients after treatment with alemtuzumab. Alemtuzumab may have some interference with platelet levels, and the mechanism may be associated with Treg cells. But due to the absence of a control group in the included literature, we cannot determine the specific impact of Alemtuzumab on platelet levels in patients with MS. Therefore, clinical physicians should perform a comprehensive assessment of the patient\'s benefit-to-risk ratio before initiating alemtuzumab.
UNASSIGNED: Inplasy website, DOI number is 10.37766/inplasy2024.3.0007.

The use of disease-modifying therapies (DMT) has led to a paradigm shift in the management of multiple sclerosis. A comprehensive narrative review was conducted through an extensive literature search including Medline and Google Scholar to elucidate the link between DMT and the propensity of cutaneous malignancies. Sphingosine-1-phosphate receptor modulators, such as fingolimod and siponimod are associated with a higher risk of basal cell carcinoma (BCC), but not squamous cell carcinoma, or melanoma. The associated physiopathological mechanisms are not fully understood. Alemtuzumab and cladribine show isolated associations with skin cancer. Regarding other DMT, no increased risk has ever been found. Given the evidence currently available, it is of paramount importance to advocate for necessary dermatological assessments that should be individualized to the risk profile of each patient. Nonetheless, additional prospective studies are still needed to establish efficient dermatological follow-up protocols.

T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response.

BACKGROUND: This article analyses the presence of gender bias in clinical trials of monoclonal antibodies used to treat multiple sclerosis.
METHODS: We performed a systematic review of controlled clinical trials of 4 monoclonal antibodies used to treat multiple sclerosis (natalizumab, rituximab, alemtuzumab, and ocrelizumab). We searched the PubMed/MEDLINE database for articles published in English before March 2020. The study was conducted in accordance with the relevant international recommendations.
RESULTS: The search identified 89 articles, 55 of which met the inclusion criteria. Of all patients included in these trials, 64.6% were women. The lead authors of 10 of the studies were women. Fifteen of the 55 studies included a sex-based analysis of the primary endpoint. Only 8 articles discussed the results separately for men and for women.
CONCLUSIONS: The clinical trials of these 4 monoclonal antibodies present a significant gender bias. In most cases, the primary and secondary endpoints are not analyzed according to patient sex, despite the fact that international recommendations include this as a minimum requirement for ensuring scientific validity and obtaining appropriate results for extrapolation to the wider population.

BACKGROUND: Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups.
METHODS: We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias.
RESULTS: Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group.
CONCLUSIONS: Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.

UNASSIGNED: Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. Monoclonal antibodies (mAbs) have shown efficacy in reducing MS relapse rates, disease progression, and brain lesion activity.
UNASSIGNED: This article reviews the literature on the use of mAbs for the treatment of MS, including their mechanisms of action, clinical trial data, safety profiles, and long-term outcomes. The review focuses on the three main categories of mAbs used in MS: alemtuzumab, natalizumab, and anti-CD20 drugs. A literature search was conducted using relevant keywords and guidelines and reports from regulatory agencies were reviewed. The search covered studies published from inception to 31 December 202231 December 2022. The article also discusses the potential risks and benefits of these therapies, including their effects on infection rates, malignancies, and vaccination efficacy.
UNASSIGNED: Monoclonal antibodies have revolutionized the treatment of MS, but safety concerns must be considered, particularly with regards to infection rates, malignancy risk, and vaccination efficacy. Clinicians must weigh the potential benefits and risks of mAbs on an individual patient basis, taking into account factors such as age, disease severity, and comorbidities. Ongoing monitoring and surveillance are essential to ensure the long-term safety and effectiveness of monoclonal antibody therapies in MS.

Aim: To assess the relative efficacy of disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) including newer therapies (ozanimod, ponesimod, ublituximab) using network meta-analysis (NMA). Materials & methods: Bayesian NMAs for annualised relapse rate (ARR) and time to 3-month and 6-month confirmed disability progression (3mCDP and 6mCDP) were conducted. Results: For each outcome, the three most efficacious treatments versus placebo were monoclonal antibody (mAb) therapies: alemtuzumab, ofatumumab, and ublituximab for ARR; alemtuzumab, ocrelizumab, and ofatumumab for 3mCDP; and alemtuzumab, natalizumab, and either ocrelizumab or ofatumumab (depending on the CDP definition used for included ofatumumab trials) for 6mCDP. Conclusion: The most efficacious DMTs for RMS were mAb therapies. Of the newer therapies, only ublituximab ranked among the three most efficacious treatments (for ARR).

BACKGROUND: Progressive multiple sclerosis (PMS) is a debilitating condition characterized by progressively worsening symptoms. Monoclonal antibodies are novel therapies for MS, but their safety and efficacy in the progressive form have not been comprehensively studied. In this systematic review, we aimed to evaluate the available evidence regarding monoclonal antibody treatment for PMS.
METHODS: After registration of the study protocol in PROSPERO, we systematically searched three major databases for clinical trials involving monoclonal antibodies administration for PMS treatment. All the retrieved results were imported into the EndNote reference manager. After removing the duplicates, two independent researchers did the study selection and data extraction. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist.
RESULTS: Of the 1846 studies in the preliminary search, 13 clinical trials investigating monoclonal antibodies (Ocrelizumab, Natalizumab, Rituximab, and Alemtuzumab) in PMS patients were included. Ocrelizumab was significantly effective in reducing clinical disease progression measures in primary PMS patients. The results for Rituximab were not completely reassuring and only showed significant changes for some endpoints on MRI and clinical measures. Natalizumab decreased the relapse rate and improved MRI features for secondary PMS patients, but not clinical endpoints. The studies on Alemtuzumab treatment revealed conflicting outcomes, with improvements observed in MRI endpoints but clinical worsening in patients. Additionally, among the studied adverse events, upper respiratory infections, urinary tract infections, and nasopharyngitis were frequently reported.
CONCLUSIONS: Based on our findings, Ocrelizumab is the most efficient monoclonal antibody for primary PMS, although it is associated with a higher risk of infection. While other monoclonal antibodies did not show significant promise in treating PMS, more research is necessary.