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Transplantation May 2006Alemtuzumab (Campath-1H) is a powerful antilymphocyte antibody that produces profound and long-lasting lymphopenia. It is being used with increasing frequency for... (Review)
Review
Alemtuzumab (Campath-1H) is a powerful antilymphocyte antibody that produces profound and long-lasting lymphopenia. It is being used with increasing frequency for induction in organ transplantation, with the aim of allowing steroid-free and/or calcineurin-free/sparing maintenance immunosuppressive protocols. Despite a considerable experience with this agent, mostly in kidney transplantation, there are only two relatively small randomized controlled trials available, and therefore the level of evidence for its role in transplantation is limited. Nevertheless, it does appear that the incidence of acute rejection is low after induction with alemtuzumab, perhaps if used with a calcineurin inhibitor, and that steroid-free and calcineurin-sparing protocols are possible. Although there is a profound and long-lasting T cell lymphopenia after administration of alemtuzumab, there is no apparent increase in infection, posttransplantation lymphoproliferative disease, or other side effects, other than perhaps autoimmune disease. Whether alemtuzumab is more effective than Thymoglobulin or anti-interleukin 2 receptor antibodies cannot be answered at this time. However from a cost aspect, the use of alemtuzumab for induction compares more than favorably with other lymphocyte-depleting agents. Alemtuzumab is an attractive agent for induction in organ transplantation, but there is a need for more and larger randomized trials with long-term follow-up before its true role can be established, particularly with respect to safety.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Calcineurin Inhibitors; Graft Rejection; Humans; Immunosuppressive Agents; Organ Transplantation; Steroids; Transplantation Conditioning
PubMed: 16732169
DOI: 10.1097/01.tp.0000219235.97036.9c -
Journal of Neurology Dec 2020Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The treatment of MS has always been a focus of neurological research. To... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and acceptability of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis: a systematic review and network meta-analysis.
BACKGROUND
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The treatment of MS has always been a focus of neurological research. To date, the US Food and Drug Administration has approved 15 medications for modifying the course of multiple sclerosis. In this study, we examined the effects of disease-modifying therapies (DMTs) on clinical outcomes.
METHODS
We did a systematic review and network meta-analysis based on randomized controlled trials (RCTs) comparing DMTs in patients with relapsing-remitting multiple sclerosis (RRMS). We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for RCTs published up to Oct 31, 2018. The primary outcome was efficacy (relapse rate over 24 months) and acceptability (treatment discontinuation due to adverse events over 24 months).
FINDINGS
We identified 23 suitable trials encompassing 14,096 participants. During the 2 years of follow-up, all drugs were significantly more effective than were placebos. The risk ratios with 95% credible intervals were as follows: alemtuzumab, 0.49 (0.40, 0.59); ocrelizumab, 0.49 (0.40, 0.61); mitoxantrone, 0.47 (0.27, 0.80); natalizumab, 0.51 (0.43, 0.61); fingolimod, 0.57 (0.50, 0.65); peginterferon beta-1a, 0.63 (0.52, 0.77); dimethyl fumarate, 0.65 (0.56, 0.74); teriflunomide 14 mg, 0.78 (0.66, 0.92); glatiramer acetate, 0.80 (0.72, 0.89); IFN β-1a (Rebif), 0.81 (0.72, 0.90); IFN β-1b (Betaseron), 0.81 (0.72, 0.91); teriflunomide 7 mg, 0.83 (0.71, 0.98); and IFN β-1a (Avonex). 0.87 (0.77, 0.99). Risk ratios compared with placebo for discontinuation due to adverse events ranged from 1.12 for the best drug (fingolimod) to 0.10 for the worst drug (mitoxantrone); from 0.24 (alemtuzumab) to 0.89 (IFNβ-1b [Betaseron]) for sustained (3-month) disability progression; and from 0.85 (natalizumab) to 1.25 (teriflunomide 14 mg) for the number of participants with serious adverse events.
INTERPRETATION
All DMTs were superior to placebo in reducing the relapse rate during the 2 years of follow-up. As to the comparison between drugs, alemtuzumab, ocrelizumab, natalizumab and fingolimod had a relatively higher response and lower dropout rates than did the other DMTs.
Topics: Fingolimod Hydrochloride; Glatiramer Acetate; Humans; Immunosuppressive Agents; Interferon beta-1a; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Network Meta-Analysis
PubMed: 31129710
DOI: 10.1007/s00415-019-09395-w -
Frontiers in Pharmacology 2022Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections. Provide a pooled estimate of the cumulative incidence for...
Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections. Provide a pooled estimate of the cumulative incidence for infections that fulfilled the criteria associated with severe infectious adverse events for grade 3 or higher (including pneumonia, febrile neutropenia and sepsis) in patients who receive targeted therapies. We searched PubMed and EMBASE for randomized controlled trials (RCT) that included patients with CLL/SLL who received targeted therapies and performed a random-effects meta-analysis to estimate the cumulative incidence of infections. Of 2,914 studies screened, we retrieved 31 which evaluated 11,660 patients. The pooled cumulative incidence of infections for patients who received treatment regimens based on a BTK inhibitors was 19.86%. For patients who received treatment based on rituximab and second generation anti-CD20 monoclonal antibodies, the pooled cumulative incidence of infections was 19.85 and 13.46%, respectively. Regarding PI3K inhibitor-based regimens the cumulative incidence of severe infections was 30.89%. BCL-2 inhibitors had a cumulative incidence of infections of 17.49% while lenalidomide and alemtuzumab had an incidence of 13.33 and 45.09%, respectively. The cumulative incidence of pneumonia ranged from 3.01 to 8.45% while febrile neutropenia ranged from 2.68 to 10.80%. Regarding sepsis, the cumulative incidence ranged from 0.9 to 4.48%. Patients with CLL/SLL who receive targeted therapies may develop severe infections at significant rates that, in addition to disease stage and other complications, depend on the mechanism of action of the used drug. Surveillance for infections and development of effective prophylactic strategies are critical for patients with CLL/SLL who receive targeted therapies. [https://systematicreview.gov/], identifier [registration number].
PubMed: 36188587
DOI: 10.3389/fphar.2022.989830 -
Current Medical Research and Opinion Aug 2018To assess the comparative efficacy and safety of cladribine tablets versus alternative disease modifying treatments (DMTs) in patients with active relapsing-remitting... (Comparative Study)
Comparative Study
OBJECTIVE
To assess the comparative efficacy and safety of cladribine tablets versus alternative disease modifying treatments (DMTs) in patients with active relapsing-remitting multiple sclerosis (RRMS), and in a subgroup with high disease activity (HRA + DAT), using systematic literature review (SLR) and network meta-analysis (NMA).
METHODS
MEDLINE, Embase, MEDLINE In-Process and CENTRAL databases were systematically searched to identify English-language publications of relevant studies of approved DMTs for RRMS. Searches were conducted from database inception to January 2017. Conference websites and trial registries were also searched. NMA considered the effects of DMTs on annualized relapse rate (ARR), confirmed disease progression (CDP), no evidence of disease activity (NEDA) and safety.
RESULTS
Of 10,825 articles retrieved and screened, 44 studies assessing 12 DMTs contributed to the NMA. In patients with active RRMS, cladribine tablets were associated with a significant 58% reduction in ARR versus placebo (p < .05); cladribine tablets were similar or significantly better than other DMT regimens and ranked fourth among DMTs, behind alemtuzumab, natalizumab and ocrelizumab. For CDP for 6 months and NEDA, improvements with cladribine tablets were significantly greater than those of placebo (p < .05), with no comparator DMT demonstrating significantly better results. Similar findings were reported in the HRA + DAT population. Overall adverse event risk for cladribine tablets did not differ significantly from that of placebo and most alternative DMTs.
CONCLUSION
In this first NMA to consider cladribine tablets, ocrelizumab and daclizumab for treatment of RRMS, cladribine tablets are a comparatively effective and safe alternative to other DMTs in both active RRMS and HRA + DAT populations.
Topics: Alemtuzumab; Cladribine; Humans; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Network Meta-Analysis; Tablets
PubMed: 29149804
DOI: 10.1080/03007995.2017.1407303 -
Multiple Sclerosis and Related Disorders Sep 2016Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies.
OBJECTIVE
To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS.
METHODS
A systematic review identified 28 randomised, placebo-controlled and direct comparative trials. A network meta-analysis was conducted within a Bayesian framework to estimate comparative annualised relapse rates (ARR) and risks of disability progression (defined by both a 3-month, and 6-month confirmation interval). Potential sources of treatment-effect modification from study-level covariates and baseline risk were evaluated through meta-regression methods. The Surface Under the Cumulative RAnking curve (SUCRA) method was used to provide a ranking of treatments for each outcome.
RESULTS
The magnitude of ARR reduction varied between 15-36% for all interferon-beta products, glatiramer acetate and teriflunomide, and from 50 to 69% for alemtuzumab, dimethyl fumarate, fingolimod and natalizumab. The risk of disability progression (3-month) was reduced by 19-28% with interferon-beta products, glatiramer acetate, fingolimod and teriflunomide, by 38-45% for pegylated interferon-beta, dimethyl fumarate and natalizumab and by 68% with alemtuzumab. Broadly similar estimates for the risk of disability progression (6-month), with the exception of interferon-beta-1b 250mcg which was much more efficacious based on this definition. Alemtuzumab and natalizumab had the highest SUCRA scores (97% and 95% respectively) for ARR, while ranking for disability progression varied depending on the definition of the outcome. Interferon-beta-1b 250mcg ranked among the most efficacious treatments for disability progression confirmed after six months (92%) and among the least efficacious when the outcome was confirmed after three months (30%). No significant modification of relative treatment effects was identified from study-level covariates or baseline risk.
CONCLUSION
Compared with placebo, clear reductions in ARR with disease-modifying therapies were accompanied by more uncertain changes in disability progression. The magnitude of the reduction and the uncertainty associated with treatment effects varied between DMTs. While natalizumab and alemtuzumab demonstrated consistently high ranking across outcomes, with older interferon-beta and glatiramer acetate products ranking lowest, variation in disability progression definitions lead to variation in the relative ranking of treatments. Rigorously conducted comparative studies are required to fully evaluate the comparative treatment effects of disease modifying therapies for RRMS.
Topics: Humans; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 27645339
DOI: 10.1016/j.msard.2016.06.001 -
Neurologia I Neurochirurgia Polska 2022This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS),... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR).
CLINICAL RATIONALE FOR THE STUDY
Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) - an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records.
MATERIAL AND METHODS
A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied.
RESULTS
Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data - HR (95% Crl - Bayesian Credibility Interval) vs. FTY: 4.98 (2.11-11.79); vs. NAT: 3.12 (1.31-7.27); vs. ALE: 9.29 (3.40-25.21). The main results were confirmed in the sensitivity analyses.
CONCLUSIONS
Of all considered therapies, treatment with cladribine tablets was associated with a higher probability of sustained disability improvement in RRMS patients. As this conclusion is based on available clinical data of limited quality, future studies, as well as real-world data, would be valuable to provide further evidence regarding the comparative effectiveness of RRMS therapies.
Topics: Humans; Cladribine; Multiple Sclerosis; Immunosuppressive Agents; Network Meta-Analysis; Retrospective Studies; Bayes Theorem; Multiple Sclerosis, Relapsing-Remitting; Tablets
PubMed: 36421066
DOI: 10.5603/PJNNS.a2022.0068 -
Seminars in Arthritis and Rheumatism Feb 2014Relapses and failure are frequent in systemic vasculitis (SV) patients. Biological agents have been prescribed as rescue therapies. The aim of this systematic review is... (Review)
Review
OBJECTIVE
Relapses and failure are frequent in systemic vasculitis (SV) patients. Biological agents have been prescribed as rescue therapies. The aim of this systematic review is to analyze the current evidence on the therapeutic use of biological agents for SV.
METHODS
MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to the end of April 2013. Systematic reviews and meta-analysis, clinical trials, cohort studies, and case series with >3 patients were included. Independent article review and study quality assessment was done by 2 investigators with consensus resolution of discrepancies.
RESULTS
Of 3447 citations, abstracts, and hand-searched studies screened, 90 were included. Most of the studies included ANCA-associated vasculitis (AAV) patients and only a few included large vessel vasculitis (LVV) patients. Rituximab was the most used agent, having demonstrated efficacy for remission induction in patients with AAV. A number of studies used different anti-TNFα agents with contrasting results. A few uncontrolled studies on the use of abatacept, alemtuzumab, mepolizumab, and tocilizumab were found.
CONCLUSION
Current evidence on the use of biological therapies for SV is mainly based on uncontrolled, observational data. Rituximab is not inferior to cyclophosphamide for remission induction in AAV and might be superior in relapsing disease. Infliximab and adalimumab are effective as steroid-sparing agents. Etanercept is not effective to maintain remission in patients with granulomatosis with polyangiitis, and serious adverse events have been reported. For LVV, both infliximab and etanercept had a role as steroid-sparing agents, and tocilizumab might be effective also for remission induction in LVV.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Biological Products; Humans; Immunosuppressive Agents; Infliximab; Remission Induction; Rituximab; Systemic Vasculitis; Treatment Outcome
PubMed: 23978781
DOI: 10.1016/j.semarthrit.2013.07.010 -
Frontiers in Neurology 2024The purpose of this study was to evaluate the risk of secondary immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab through a meta-analysis.
OBJECT
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
SYSTEMATIC REVIEW REGISTRATION
Inplasy website, DOI number is 10.37766/inplasy2024.3.0007.
PubMed: 38660089
DOI: 10.3389/fneur.2024.1375615 -
The Cochrane Database of Systematic... Apr 2016Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. However, at present there is no effective treatment that is capable of safely and effectively reaching these objectives. This has led to the development and investigation of new drugs. Recent clinical trials suggest that alemtuzumab, a humanised monoclonal antibody against cell surface CD52, could be a promising option for MS.
OBJECTIVES
To assess the safety and effectiveness of alemtuzumab used alone or associated with other treatments to decrease disease activity in patients with any form of MS.
SEARCH METHODS
We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (30 April 2015), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. There was no restriction on the source, publication date or language.
SELECTION CRITERIA
All randomised clinical trials (RCTs) involving adults diagnosed with any form of MS according to the McDonald criteria, comparing alemtuzumab alone or associated with other medications, at any dose and for any duration, versus placebo or any other active drug therapy or alemtuzumab in other dose, regimen or duration. The co-primary outcomes were relapse-free survival, sustained disease progression and number of participants with at least one of any adverse events, including serious adverse events.
DATA COLLECTION AND ANALYSIS
Two independent review authors performed study selection, data extraction and 'Risk of bias' assessment. A third review author checked the process for accuracy. We used the Cochrane 'Risk of bias' tool to assess the risk of bias of the studies included in the review. We used the GRADE system to assess the quality of the body of evidence. To measure the treatment effect on dichotomous outcomes we used the risk ratio (RR); for the treatment effect on continuous outcomes, we used the mean difference (MD) and for time-to-event outcomes we used hazard ratio (HR). We calculated 95% confidence intervals (CI) for these measures. When there was no heterogeneity, we used a fixed-effect model to pool data.
MAIN RESULTS
Three RCTs (1713 participants) fulfilled the selection criteria and we included them in the review. All three trials compared alemtuzumab versus subcutaneous interferon beta-1a for patients with relapsing-remitting MS. Patients were treatment-naive in the CARE-MS and CAMMS223 studies. The CARE-MS II study included patients with at least one relapse while being treated with interferon beta or glatiramer acetate. Alemtuzumab was given for 12 or 24 months; for some outcomes, the follow-up period reached 36 months. The regimens were (a) 12 mg or 24 mg per day administered intravenously, once a day for five consecutive days at month 0 and 12 or (b) 24 mg per day, intravenously, once a day for three consecutive days at month 12 and 24. The patients in the other arm of the trials received interferon beta-1a 44 μg subcutaneously three times weekly after dose titration.At 24 months, alemtuzumab 12 mg was associated with: (a) higher relapse-free survival (hazard ratio (HR) 0.50, 95% CI 0.41 to 0.60; 1248 participants, two studies, moderate quality evidence); (b) higher sustained disease progression-free survival (HR 0.62, 95% CI 0.44 to 0.87; 1191 participants; two studies; moderate quality evidence); (c) a slightly higher number of participants with at least one adverse event (RR 1.04, 95% CI 1.01 to 1.06; 1248 participants; two studies; moderate quality evidence); (d) a lower number of participants with new or enlarging T2-hyperintense lesions on magnetic resonance imaging (MRI) (RR 0.74, 95% CI 0.59 to 0.91; 1238 participants; two studies; I(2) = 80%); and (e) a lower number of dropouts (RR 0.31, 95% CI 0.23 to 0.41; 1248 participants; two studies, I(2) = 29%; low quality evidence).At 36 months, alemtuzumab 24 mg was associated with: (a) higher relapse-free survival (45 versus 17; HR 0.21, 95% CI 0.11 to 0.40; one study; 221 participants); (b) a higher sustained disease progression-free survival (HR 0.33, 95% CI 0.16 to 0.69; one study; 221 participants); and (c) no statistical difference in the rate of participants with at least one adverse event. We did not find any study that reported any of the following outcomes: rate of participants free of clinical disease activity, quality of life, fatigue or change in the numbers of MRI T2- and T1-weighted lesions after treatment. It was not possible to perform subgroup analyses according to disease type and disability at baseline due to lack of data.
AUTHORS' CONCLUSIONS
In patients with relapsing-remitting MS, alemtuzumab 12 mg was better than subcutaneous interferon beta-1a for the following outcomes assessed at 24 months: relapse-free survival, sustained disease progression-free survival, number of participants with at least one adverse event and number of participants with new or enlarging T2-hyperintense lesions on MRI. The quality of the evidence for these results was low to moderate. Alemtuzumab 24 mg seemed to be better than subcutaneous interferon beta-1a for relapse-free survival and sustained disease progression-free survival, at 36 months.More randomised clinical trials are needed to evaluate the effects of alemtuzumab on other forms of MS and compared with other therapeutic options. These new studies should assess additional relevant outcomes such as the rate of participants free of clinical disease activity, quality of life, fatigue and adverse events (individual rates, serious adverse events and long-term adverse events). Moreover, these new studies should evaluate other doses and durations of alemtuzumab course.
Topics: Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Disease-Free Survival; Humans; Interferon beta-1a; Multiple Sclerosis, Relapsing-Remitting; Randomized Controlled Trials as Topic
PubMed: 27082500
DOI: 10.1002/14651858.CD011203.pub2 -
Transplantation Proceedings Dec 2018Heart and lung transplantation is a high-risk procedure requiring intensive immunosuppressive therapy for preventing organ rejection. Alemtuzumab, a CD52-specific... (Meta-Analysis)
Meta-Analysis
Acute Cellular Rejection and Infection Rates in Alemtuzumab vs Traditional Induction Therapy Agents for Lung and Heart Transplantation: A Systematic Review and Meta-analysis.
BACKGROUND AND OBJECTIVES
Heart and lung transplantation is a high-risk procedure requiring intensive immunosuppressive therapy for preventing organ rejection. Alemtuzumab, a CD52-specific monoclonal antibody, is increasingly used for induction therapy compared with conventional agents. However, there has been no systematic review comparing its efficacy with traditional therapeutic drugs.
METHODS
PubMed and EMBASE were searched to October 1, 2017, for articles on alemtuzumab in cardiothoracic transplant surgery. Of the 433 studies retrieved, 8 were included in the final meta-analysis.
RESULTS
In lung transplantation, alemtuzumab use was associated with lower odds of acute cellular rejection compared with antithymocyte globulin (odds ratio [OR], 0.21; 95% CI, 0.11-0.40; P < .001), lower acute rejection rates (OR, 0.12; 95% CI, 0.03-0.55; P < .01), and infection rates (OR, 0.69; 95% CI, 0.35-1.36; P = .33) when compared with basiliximab. Multivariate meta-regression analysis found that mean age, male sex, single lung transplant, double lung transplant, cytomegalovirus or Epstein-Barr virus status, idiopathic pulmonary fibrosis, cystic fibrosis, and mean ischemic time did not significantly influence acute rejection outcomes. For heart transplantation, alemtuzumab use was associated with lower acute rejection rates when compared with tacrolimus (OR, 0.44; 95% CI, 0.30-0.66; P < .001).
CONCLUSIONS
Alemtuzumab use was associated with lower rejection rates when compared with conventional induction therapy agents (antithymocyte globulin, basiliximab, and tacrolimus) in heart and lung transplantation. However, this was based on observational studies. Randomized controlled trials are needed to verify its clinical use.
Topics: Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Lung Transplantation; Male; Middle Aged
PubMed: 30577263
DOI: 10.1016/j.transproceed.2018.08.044