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The International Journal of Risk &... 2020Disease-modifying therapies for multiple sclerosis have been developed tremendously over the last two decades. (Observational Study)
Observational Study
BACKGROUND
Disease-modifying therapies for multiple sclerosis have been developed tremendously over the last two decades.
OBJECTIVE
The aim of this study was to review the short-, medium-, and long-term safety of alemtuzumab in relapsing remitting multiple sclerosis (RRMS).
METHOD
This retrospective observational study (2015-2019) included all patients with highly active or rapidly progressing and aggressive RRMS who were treated with alemtuzumab at the Cabueñes University Hospital. The short-, medium-, and long-term adverse effects were evaluated following the risk management program of the European Medicines Agency.
RESULTS
39 patients were included, 23 of them received at least two cycles of treatment. Most patients showed at least one adverse event. The following adverse reactions were reported: infusional reactions (17), urinary tract infections (six), thrombopenia (five), and thyroid dysfunction (six).
CONCLUSION
In clinical practice alemtuzumab showed an acceptable safety profile in selected patients even if all of them suffered at least one adverse effect. Thorough and prolonged follow-up is required to further confirm the safety of this drug.
Topics: Alemtuzumab; Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence; Retrospective Studies
PubMed: 32145001
DOI: 10.3233/JRS-191029 -
Neurological Sciences : Official... Sep 2022This study aimed to compare the safety profile of high-efficacy disease-modifying therapies (DMTs) natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to compare the safety profile of high-efficacy disease-modifying therapies (DMTs) natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, as well as a potentially high-efficacy DMT, ponesimod, in adult patients with relapsing-remitting multiple sclerosis (RRMS).
METHODS
A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included randomized controlled trials (RCTs) with at least 48-week follow-up investigating the use of natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, and ponesimod, as well as other DMTs, in adult patients with RRMS. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The Cochrane Collaboration tool to assess the risk of bias for RCTs was used.
RESULTS
A total of 33 RCTs were included in the systematic review and NMA. A higher rate of adverse events (AEs) was revealed for alemtuzumab versus all other high-efficacy DMTs; for alemtuzumab (average probability of an event: 98.2%) versus placebo (86.2%); for cladribine (3.5 mg; 90.5%) versus ozanimod (1 mg; 84.2%) and placebo; as well as for ocrelizumab (95.5%) versus ozanimod, ofatumumab (88.9%), fingolimod (87.4%), natalizumab (82.8%), and placebo. No significant differences were found between drugs in terms of serious AEs except for cladribine (3.5 mg, 17.3%) versus ocrelizumab (10.3%) and ofatumumab (16.6%) versus ocrelizumab. Significant differences in AEs leading to the discontinuation of study drug were found only for ponesimod (10.1%) versus alemtuzumab (12 mg, 3.0%) and placebo (4.2%). No differences were found in terms of upper respiratory tract infections, nasopharyngitis, fatigue, and nausea between individual high-efficacy DMTs as well as between DMTs and placebo. The results of the NMA indicated a higher risk of infections for alemtuzumab (12 mg) versus ocrelizumab, for cladribine (3.5 mg) versus ofatumumab and placebo, and for ofatumumab versus placebo. For serious infections and urinary tract infections, a significant increase was found only for alemtuzumab (12 mg) versus ocrelizumab, while no differences were found between the other DMTs or between DMTs and placebo. Headache was more common for alemtuzumab (12 mg) as compared with all the other high-efficacy DMTs and placebo, as well as for cladribine versus natalizumab and fingolimod versus natalizumab.
CONCLUSION
The commonly reported AEs are generally similar among high-efficacy DMTs. However, based on P scores for most analyzed endpoints, natalizumab and ocrelizumab were shown to be the safest DMTs. Considering the limitations of indirect comparisons, further research is needed to confirm our findings, preferably head-to-head RCTs and large observational studies.
Topics: Adult; Alemtuzumab; Cladribine; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Network Meta-Analysis
PubMed: 35713731
DOI: 10.1007/s10072-022-06197-3 -
Frontiers in Immunology 2022Induction therapy is used in about 80% of lung transplant centers and is increasing globally. Currently, there are no standards or guidelines for the use of induction...
BACKGROUND
Induction therapy is used in about 80% of lung transplant centers and is increasing globally. Currently, there are no standards or guidelines for the use of induction therapy. At our institution, we have two induction strategies, basiliximab, and alemtuzumab. The goal of this manuscript is to share our experience and practice since this is an area of controversy.
METHODS
We retrospectively reviewed 807 lung transplants performed at our institution between 2011 and 2020. Indications for the use of the basiliximab protocol were as follows: patients over the age of 70 years, history of cancer, hepatitis C virus or human immunodeficiency virus infection history, and cytomegalovirus or Epstein-Barr virus (donor positive/ recipient negative). In the absence of these clinical factors, the alemtuzumab protocol was used.
RESULTS
453 patients underwent alemtuzumab induction and 354 patients underwent basiliximab. There were significant differences in delayed chest closure (24.7% alemtuzumab vs 31.4% basiliximab, p = 0.037), grade 3 primary graft dysfunction observed within 72 hours (19.9% alemtuzumab vs 29.9% basiliximab, p = 0.002), postoperative hepatic dysfunction (8.8% alemtuzumab vs 14.7% basiliximab, p = 0.009), acute cellular rejection in first year (39.1% alemtuzumab vs 53.4% basiliximab, p < 0.001). The overall survival rate of the patients with alemtuzumab induction was significantly higher than those of the patients with basiliximab induction (5 years survival rate: 64.1% alemtuzumab vs 52.3%, basiliximab, p < 0.001). Multivariate Cox regression analysis confirmed lower 5-year survival for basiliximab induction (HR = 1.41, p = 0.02), recipient cytomegalovirus positive (HR = 1.49, p = 0.01), postoperative hepatic dysfunction (HR = 2.20, p < 0.001), and acute kidney injury requiring renal replacement therapy (HR = 2.27, p < 0.001).
CONCLUSIONS
In this single center retrospective review, there was a significant difference in survival rates between induction strategies. This outcome may be attributable to differences in recipient characteristics between the groups. However, the Alemtuzumab group experienced less episodes of acute cellular rejection within the first year.
Topics: Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Basiliximab; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Transplantation; Retrospective Studies
PubMed: 35720296
DOI: 10.3389/fimmu.2022.864545 -
Journal Der Deutschen Dermatologischen... Aug 2021Alemtuzumab is currently approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). Despite the efficacy of this therapy several side effects in... (Review)
Review
Alemtuzumab is currently approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). Despite the efficacy of this therapy several side effects in the skin have been noted during or after infusion including vitiligo, alopecia areata, malignant skin tumors and infections. Awareness of these effects and their treatment is of essential interdisciplinary importance. This minireview provides an overview of the dermatological side effects described in the current literature. We also suggest pathomechanisms underlying these phenomena. To introduce this review, we present the case of a woman with RRMS who developed severe alopecia areata for the first time on alemtuzumab.
Topics: Alemtuzumab; Alopecia Areata; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Multiple Sclerosis, Relapsing-Remitting; Vitiligo
PubMed: 33973347
DOI: 10.1111/ddg.14448 -
Kidney International Jul 2021
Topics: Alemtuzumab; Glomerulonephritis, Membranous; Humans
PubMed: 34154717
DOI: 10.1016/j.kint.2021.02.030 -
Frontiers in Immunology 2020Alemtuzumab, a monoclonal antibody targeting CD52 that causes lymphocyte apoptosis, is a form of advanced immunosuppression that is currently used as a therapy for...
Alemtuzumab, a monoclonal antibody targeting CD52 that causes lymphocyte apoptosis, is a form of advanced immunosuppression that is currently used as a therapy for refractory acute cellular rejection and chronic lung allograft dysfunction in lung transplant recipients (1-3). Side effects of alemtuzumab include bone marrow suppression, infection, and malignancy. Whether alemtuzumab can be safely used in allograft recipients that have an increased propensity for bone marrow suppression due to telomeropathies is unknown. In a retrospective case series, we report outcomes associated with alemtuzumab in three lung allograft recipients with short telomere lengths, comparing endpoints such as leukopenia, transfusion needs, infection, hospitalization and survival to those of 17 patients without known telomeropathies that received alemtuzumab. We show that the use of alemtuzumab in lung transplant recipients with short telomeres is safe, though is associated with an increased incidence of neutropenia, thrombocytopenia and anemia requiring packed red blood cell transfusions. Alemtuzumab appears to be an acceptable advanced immunosuppressive therapy in patients with telomeropathies, though given the design and scope of this study, the actual clinical effect needs further evaluation in larger trials.
Topics: Alemtuzumab; Allografts; CD52 Antigen; Female; Graft Rejection; Hematologic Diseases; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Retrospective Studies; Safety; Telomere Shortening; Treatment Outcome
PubMed: 32547557
DOI: 10.3389/fimmu.2020.01063 -
Multiple Sclerosis and Related Disorders Nov 2020
Topics: Alemtuzumab; Anemia; Humans; Sarcoidosis
PubMed: 32979730
DOI: 10.1016/j.msard.2020.102526 -
Multiple Sclerosis and Related Disorders Jul 2022Background Alemtuzumab (ATZ), a highly effective disease modifying treatment for relapsing multiple sclerosis (MS), is associated with the rare risk of intracerebral...
Background Alemtuzumab (ATZ), a highly effective disease modifying treatment for relapsing multiple sclerosis (MS), is associated with the rare risk of intracerebral hemorrhage. Increase of blood pressure (BP) was hypothesized to be causative, but prior administration of high-dose methylprednisolone (HDMP) is a potential confounder. Objective To analyze BP change in MS patients treated with ATZ and prior HDMP treatment compared to patients receiving HDMP only for acute relapse. Methods In this retrospective study, 30 patients treated with ATZ/HDMP and 60 age-, sex- and disability-matched controls treated with HDMP were included. Primary endpoint was the change of systolic BP (SBP) between before ATZ cycle and the maximum value measured during the treatment cycle; secondary endpoints were change in diastolic BP (DBP) and heart rate (HR). Results Change of SBP observed in ATZ/HDMP treated patients was significantly higher than in HDMP controls (mean maximal change of 12.8 vs. 8.1 mmHg, p = 0.033). An increase of SBP exceeding 20% from baseline was observed in 5 (16.7%) patients on ATZ/HDMP compared to 3 (5.0%) on HDMP (p = 0.078). The day after the 1st ATZ infusion, mean HR was higher in the ATZ/HDMP group compared to HDMP controls (82.5 vs. 73.2 bpm, p = 0.005), although there was no significant group difference over time. Conclusions ATZ treatment induced a slight, but significant increase in SBP independent of HDMP. Although hemodynamic alterations alone seem unlikely as putative mechanism for cerebral bleedings, strict cardiovascular monitoring is recommended to reduce rare, but severe cardiovascular side effects.
Topics: Adrenal Cortex Hormones; Alemtuzumab; Blood Pressure; Humans; Methylprednisolone; Multiple Sclerosis; Premedication; Recurrence; Retrospective Studies
PubMed: 35477127
DOI: 10.1016/j.msard.2022.103810 -
Journal of Neurology, Neurosurgery, and... Dec 2021
Topics: Alemtuzumab; Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Neuroprotective Agents; Remyelination
PubMed: 34667100
DOI: 10.1136/jnnp-2021-326821 -
Immunology Jun 2018Alemtuzumab is a lymphocyte-depleting antibody and one of the most effective treatments for relapsing multiple sclerosis. However, it also causes loss of...
Alemtuzumab is a lymphocyte-depleting antibody and one of the most effective treatments for relapsing multiple sclerosis. However, it also causes loss of immune-tolerance leading to secondary autoimmunity and marked anti-drug antibody responses. Although these anti-drug responses have been reported to be of no significance, we hypothesized that they will affect the depleting capacity and treatment response in some individuals. This was found following analysis of the regulatory submission of the pivotal phase III trials, which was obtained from the European Medicines Agency. At the population level there was lack of influence of 'ever-positive' alemtuzumab-specific antibody responses on lymphocyte depletion, clinical efficacy and adverse effects during the 2-year trial. This was not surprising as no one before the first infusion, and only 0·6% of people before the second-infusion, had pre-infusion, neutralizing antibodies (NAbs). However, at the individual level, NAbs led to poor lymphocyte depletion. Importantly, it was evident that 31% of people had NAbs and 75% had binding antibodies at the end of treatment-cycle 2, which suggests that problems may occur in people requiring additional alemtuzumab cycles. In addition, we also identified individuals, following 'post-marketing' alemtuzumab use, whose lymphocyte level was never effectively depleted after the first infusion cycle. Hence, although alemtuzumab depletes lymphocytes in most individuals, some people fail to deplete/deplete poorly, probably due to biological-response variation and NAbs, and this may lead to treatment failure. Monitoring depletion following infusion and assessment of the neutralizing response before re-infusion may help inform the decision to retreat or switch therapy to limit treatment failure.
Topics: Alemtuzumab; Antibodies, Neutralizing; Humans; Lymphocyte Depletion; Multiple Sclerosis; Treatment Failure; Treatment Outcome
PubMed: 29247512
DOI: 10.1111/imm.12879