Management of worsening multiple sclerosis with mitoxantrone: a review.


BACKGROUND:Mitoxantrone, an intravenously administered immunosuppressant that inhibits T-cell, B-cell, and macrophage proliferation, is indicated for reducing neurologic disability and relapse frequency in patients with secondary progressive multiple sclerosis (SPMS), progressive relapsing MS, or worsening relapsing-remitting MS (RRMS). OBJECTIVE:This article reviews the pathogenesis and natural history of MS and examines the available treatment options for patients with RRMS, worsening RRMS, or SPMS, with a focus on mitoxantrone. METHODS:MEDLINE (1966-present) and the Cochrane Central Register of Controlled Trials (1994-present) were searched for relevant randomized, blinded, controlled clinical trials using the terms mitoxantrone, Novantrone, and multiple sclerosis. RESULTS:Five randomized, blinded, controlled trials and an ongoing open-label Phase IV safety study were identified and included in this review. In one randomized, double-blind trial (N=25), patients with RRMS who received mitoxantrone 8 mg/m2 monthly had significantly reduced relapse rates at 1 year compared with those who received placebo (P=0.014). In a 2-year, randomized, partially blinded trial (N=51), patients with active RRMS who received mitoxantrone 8 mg/m2 monthly had significantly fewer relapses compared with those who received placebo (P<0.001), and significantly fewer patients had confirmed progression of disability (1-point increase in Expanded Disability Status Scale [EDSS] score) (P=0.02). In a randomized, double-blind trial (N=49), patients with relapsing SPMS who received mitoxantrone 12 mg/m2 monthly for 3 months followed by 12 mg/m2 g3mo for up to 32 months had significant improvements in EDSS scores compared with those who received methylprednisolone 1 g IV monthly for 3 months followed by 1 g IV g3mo (P=0.002 at 1 year, P=0.045 at 2 years) and significant reductions in the number of gadolinium-enhancing lesions on magnetic resonance imaging (MRI) (P=0.002 at 1 and 2 years, P=0.03 at 3 years). In a randomized, partially blinded Phase II trial in 42 patients with active RRMS or SPMS, patients who received mitoxantrone 20 mg IV monthly and methylprednisolone 1 g IV monthly had significantly fewer new gadolinium-enhancing lesions on MRI (P<0.001) and significantly fewer relapses (P<0.01) at 6 months compared with those who received methylprednisolone alone. In a pivotal Phase III trial (N=194), patients with worsening RRMS or SPMS who received mitoxantrone 12 mg/m2 g3mo for 2 years had significantly fewer relapses (P<0.001) and significantly less deterioration in disability, as measured by change in EDSS score (P=0.019), compared with those who received placebo. In a nonrandomized subgroup of patients from this study (n=110), those who received mitoxantrone 12 mg/m2 g3mo had a significant reduction in the number of T2-weighted MRI lesions at 24 months (P=0.027). The most common adverse events in these studies included nausea and/or vomiting (18%-85%), alopecia (33%-61%), amenorrhea (8%-53%), urinary tract infections (6%-32%), and upper respiratory tract infections (4%-53%). Leukopenia was reported in 10% to 19% of patients. Use of mitoxantrone can lead to serious adverse effects, particularly cardiotoxicity, myelosuppression, and, rarely, leukemia. Long-term use of mitoxantrone may compromise left ventricular function. Limited cardiotoxicity was reported in the clinical studies; in the pivotal clinical trial, 2 patients who received mitoxantrone 12 mg/m2 had decreases in left ventricular ejection fraction to <50% of baseline. CONCLUSIONS:In the available clinical trials, mitoxantrone provided effective treatment for worsening RRMS or SPMS. When mitoxantrone is used as recommended, the risks of substantial myelosuppressive and cardiotoxic effects can be reduced by careful patient selection, drug administration, and monitoring. The lifetime cumulative dose should be strictly limited to 140 mg/m2, or 2 to 3 years of therapy.


Clin Ther


Clinical therapeutics


Fox EJ




Has Abstract


2006-04-01 00:00:00














  • Gangrenous and perforated appendicitis with peritonitis: treatment and bacteriology.

    abstract::A comparison of single-agent antimicrobial therapy in the treatment of patients with perforated or gangrenous appendicitis and peritonitis was performed in a double-blind, randomized, prospective trial. Pathologic documentation of advanced appendicitis and positive intraoperative specimen cultures were required for in...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Bennion RS,Thompson JE,Baron EJ,Finegold SM

    更新日期:1990-01-01 00:00:00

  • Single-Center Analysis of the Potential Inappropriate Use of Intravenous Medications in Hospitalized Patients in China.

    abstract::This study categorizes the types of inappropriate intravenous prescriptions in hospitalized patients in China. Prescription data from 2016 were retrospectively analyzed based on predefined categories of inappropriateness. Of the 123,521 patients included, 89.2% received intravenous medications, contributing to 80% of ...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Zeng S,Wang D,Yan Y,Zhu M,Liu W,Gong Z,Wang L,Sun S

    更新日期:2019-08-01 00:00:00

  • Effect of combined systemic and local morpholino treatment on the spinal muscular atrophy Δ7 mouse model phenotype.

    abstract:BACKGROUND:Spinal muscular atrophy (SMA) is a fatal motor neuron disease of childhood that is caused by mutations in the SMN1 gene. Currently, no effective treatment is available. One possible therapeutic approach is the use of antisense oligos (ASOs) to redirect the splicing of the paralogous gene SMN2, thus increasin...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Nizzardo M,Simone C,Salani S,Ruepp MD,Rizzo F,Ruggieri M,Zanetta C,Brajkovic S,Moulton HM,Müehlemann O,Bresolin N,Comi GP,Corti S

    更新日期:2014-03-01 00:00:00

  • Why Are We Still Creating Individual Case Safety Reports?

    abstract::The history of drug safety monitoring, or pharmacovigilance, has been an interesting one. Despite many and ongoing changes, it has typically been characterized by a rather slow-moving and reactive progression. Pharmacovigilance has always lagged behind other fields and industries and has been slow to adapt to new appr...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Streefland MB

    更新日期:2018-12-01 00:00:00

  • Potential drug-drug interaction between interferon alfa-2b and gemfibrozil in a patient with malignant melanoma.

    abstract:BACKGROUND:In the United States, patients with high-risk stage II or III melanoma are often treated with adjuvant interferon (IFN) therapy for 1 year after surgery. Adverse events associated with IFN alfa-2b use are primarily constitutional symptoms. However, hypertriglyceridemia requiring treatment has been reported. ...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Wong SF,Jakowatz JG,Taheri R

    更新日期:2005-12-01 00:00:00

  • Long-term Clinical and Cost Outcomes of a Pharmacist-managed Risk Factor Management Clinic in Singapore: An Observational Study.

    abstract:PURPOSE:Few studies have determined the benefits of pharmacist-run clinics within a tertiary institution, and specifically on their capability to improve clinical outcomes as well as reduce the cost of illness. This study was designed to investigate the effectiveness of a pharmacist-managed risk factor management clini...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Tan SH,Kng KK,Lim SM,Chan A,Loh JKK,Lee JY

    更新日期:2017-12-01 00:00:00

  • Application of concentration ratios to analyze the phenomenon of "next-door" pharmacy in Taiwan.

    abstract:BACKGROUND:In Taiwan, a policy of separation of prescribing and dispensing practices of practitioners at Western medical and dental clinics was implemented on an incremental basis in 1997. The purpose of this policy was to promote pharmacists' autonomy and increase the transparency and safety of prescribing medications...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Ji Chen T,Chou LF,Hwang SJ

    更新日期:2006-08-01 00:00:00

  • The cost of treating community-acquired pneumonia.

    abstract::Community-acquired pneumonia (CAP) is responsible for an average of 4.5 million visits annually to physicians' offices, emergency departments, and outpatient clinics. However, there have been few studies using national data on the costs of treating CAP. Without such data, it is difficult to assess whether new therapie...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Niederman MS,McCombs JS,Unger AN,Kumar A,Popovian R

    更新日期:1998-07-01 00:00:00

  • Remission versus response as the goal of therapy in ADHD: a new standard for the field?

    abstract:BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) has a substantial negative impact; however, within long-term follow-up studies, a proportion of patients do very well, both symptomatically and functionally, suggesting that the lower the symptom burden, the greater the functional improvements. Studies in major...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审


    authors: Steele M,Jensen PS,Quinn DM

    更新日期:2006-11-01 00:00:00

  • Eltrombopag: an oral thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura.

    abstract:BACKGROUND:Idiopathic thrombocytopenic purpura (ITP) is a relatively rare acquired autoimmune disease characterized by either decreased platelet production or increased platelet destruction leading to reduced platelet counts and increased risk of bleeding. Immune modulators have been used in treatment; however, a novel...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审


    authors: Zhang Y,Kolesar JM

    更新日期:2011-11-01 00:00:00

  • Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients.

    abstract:BACKGROUND:Venous thromboembolism (VTE) prophylaxis in medically ill patients has received a level 1A recommendation in previously published clinical guidelines. Pharmacologic prophylaxis for VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux. Few direct comparisons between...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,meta分析,评审


    authors: Kanaan AO,Silva MA,Donovan JL,Roy T,Al-Homsi AS

    更新日期:2007-11-01 00:00:00

  • Use of anesthesia selection in controlling surgery costs in an HMO hospital.

    abstract::The cost of induction and maintenance of anesthesia is analyzed in this article from the perspective of a health maintenance organization's (HMO) chief financial officer. While earlier economic studies tended to focus on the raw cost of anesthesia drugs, our model also includes the cost of the clinical labor involved ...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Suver J,Arikian SR,Doyle JJ,Sweeney SW,Hagan M

    更新日期:1995-05-01 00:00:00

  • Differences in adherence to osteoporosis regimens: a 2-year analysis of a population treated under specific guidelines.

    abstract:BACKGROUND:Patients' adherence to antiosteoporotic drug therapy is essential to prevent fracture and complications of osteoporosis over the long term. The guidance given in treating osteoporosis can potentially enhance adherence. OBJECTIVE:This study was conducted to compare adherence to osteoporosis regimens by patie...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Cheng TT,Yu SF,Hsu CY,Chen SH,Su BY,Yang TS

    更新日期:2013-07-01 00:00:00

  • Effects of lisuride hydrogen maleate on ischemia-induced depletion of brain acetylcholine levels in gerbils.

    abstract::Effects of several cerebral metabolic activators on ischemia-induced decrease in brain acetylcholine levels were studied in gerbils. Single administration of lisuride hydrogen maleate (lisuride) significantly inhibited ischemia-induced decreases in acetylcholine in the hippocampus among various regions of the brain in...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Ogawa N,Haba K,Yoshikawa H,Kawata M,Sato H

    更新日期:1989-03-01 00:00:00

  • Effect of multidrug resistance gene-1 (ABCB1) polymorphisms on the single-dose pharmacokinetics of cloxacillin in healthy adult Chinese men.

    abstract:BACKGROUND:Plasma concentrations of cloxacillin have been found to vary as much as 20-fold among individuals receiving the same oral dose. There is evidence that cloxacillin may be a substrate for P-glycoprotein, suggesting that polymorphisms in the ABCB1 gene may be a contributing factor to the observed variability in...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Yin OQ,Tomlinson B,Chow MS

    更新日期:2009-05-01 00:00:00

  • Cost-effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the United States.

    abstract:BACKGROUND:Prophylaxis with granulocyte colony-stimulating factor reduces the risk for febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. OBJECTIVE:We estimated the incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 of chemotherapy) with pegfilgrastim versus filgrasti...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Lyman GH,Lalla A,Barron RL,Dubois RW

    更新日期:2009-05-01 00:00:00

  • Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Losartan Trial Investigators.

    abstract:OBJECTIVE:The goal of this multicenter, double-blind, randomized, parallel-group study was to compare the effects of losartan potassium (hereafter referred to as losartan), candesartan cilexitil (hereafter referred to as candesartan), and losartan/hydrochlorothiazide (HCTZ) in patients with mild to moderate hypertensio...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Manolis AJ,Grossman E,Jelakovic B,Jacovides A,Bernhardi DC,Cabrera WJ,Watanabe LA,Barragan J,Matadamas N,Mendiola A,Woo KS,Zhu JR,Mejia AD,Bunt T,Dumortier T,Smith RD

    更新日期:2000-10-01 00:00:00

  • Efficacy and safety of morning versus evening dose of controlled-release simvastatin tablets in patients with hyperlipidemia: a randomized, double-blind, multicenter phase III trial.

    abstract:BACKGROUND:Flexibility in the recommended dosing time for a statin may improve patient compliance. OBJECTIVE:This study was designed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia. It was carried out as a requirement to obtain ...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Kim SH,Kim MK,Seo HS,Hyun MS,Han KR,Cho SW,Kim YK,Hoon Park S

    更新日期:2013-09-01 00:00:00

  • A Phase III, Randomized, Placebo-controlled Trial to Assess the Efficacy and Safety of Once-daily SPN-812 (Viloxazine Extended-release) in the Treatment of Attention-deficit/Hyperactivity Disorder in School-age Children.

    abstract:PURPOSE:The limitations of current US Food and Drug Administration (FDA)-approved medications for the treatment of attention-deficit/hyperactivity disorder (ADHD) set the need for the development of novel, effective, and tolerable medications to treat this disorder. The purpose of this study was to evaluate whether tre...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,随机对照试验


    authors: Nasser A,Liranso T,Adewole T,Fry N,Hull JT,Chowdhry F,Busse GD,Cutler AJ,Jones NJ,Findling RL,Schwabe S

    更新日期:2020-08-01 00:00:00

  • Pharmacokinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149: double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects.

    abstract:BACKGROUND:PHX1149 is a dipeptidyl peptidase-4 (DPP4) inhibitor that is currently in clinical development for the treatment of type 2 diabetes mellitus. PHX1149 is a small (molecular weight = 241.16 Da), highly water-soluble (>2 g/mL), orally active molecule with a selectivity index of 15- to 319-fold relative to those...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,随机对照试验


    authors: O'Farrell AM,van Vliet A,Abou Farha K,Cherrington JM,Campbell DA,Li X,Hanway D,Li J,Guler HP

    更新日期:2007-08-01 00:00:00

  • An In-home Advanced Robotic System to Manage Elderly Home-care Patients' Medications: A Pilot Safety and Usability Study.

    abstract:PURPOSE:We examined the safety profile and usability of an integrated advanced robotic device and telecare system to promote medication adherence for elderly home-care patients. METHODS:There were two phases. Phase I aimed to verify under controlled conditions in a single nursing home (n = 17 patients) that no robotic...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Rantanen P,Parkkari T,Leikola S,Airaksinen M,Lyles A

    更新日期:2017-05-01 00:00:00

  • Ceftazidime/metronidazole versus netilmicin/metronidazole in the treatment of perforated appendicitis in children.

    abstract::One hundred children with peritonitis resulting from a perforated appendix were treated with ceftazidime or netilmicin. Metronidazole was added to both groups to treat the anaerobic organisms commonly associated with the infecting aerobic organisms in peritonitis. Escherichia coli was the most common aerobe found in p...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Kooi GH,Pit S

    更新日期:1990-01-01 00:00:00

  • Dosage Optimization of Efavirenz Based on a Population Pharmacokinetic-Pharmacogenetic Model of HIV-infected Patients in Thailand.

    abstract:PURPOSE:Efavirenz exhibits high interindividual variability in plasma concentrations, leading to unpredictable efficacy and toxicity. Polymorphism of CYP2B6 516G > T has been found to predominantly contribute to efavirenz variability. However, dosage recommendations incorporating CYP2B6 516G > T polymorphism have not b...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Chaivichacharn P,Avihingsanon A,Manosuthi W,Ubolyam S,Tongkobpetch S,Shotelersuk V,Punyawudho B

    更新日期:2020-07-01 00:00:00

  • Effect of daily and intermittent use of ibandronate on bone mass and bone turnover in postmenopausal osteoporosis: a review of three phase II studies.

    abstract:BACKGROUND:Oral bisphosphonates are well established for the treatment and prevention of postmenopausal osteoporosis; however, they are poorly absorbed from the gastrointestinal (GI) tract and have been associated with GI adverse events. Thus, current dosing guidelines recommend that the patient not eat or lie down for...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审


    authors: Schimmer RC,Bauss F

    更新日期:2003-01-01 00:00:00

  • Correspondence between the RAND-Negative Impact of Asthma on Quality of Life item bank and the Marks Asthma Quality of Life Questionnaire.

    abstract:BACKGROUND:In many research and clinical settings in which patient-reported outcome (PRO) measures are used, it is often desirable to link scores across disparate measures or to use scores from 1 measure to describe scores on a separate measure. However, PRO measures are scored by using a variety of metrics, making suc...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Edelen MO,Stucky BD,Sherbourne C,Eberhart N,Lara M

    更新日期:2014-05-01 00:00:00

  • Role of Intestinal Microbiome in Lipid and Glucose Metabolism in Diabetes Mellitus.

    abstract:PURPOSE:The contribution of intestinal bacterial strains (gut microbiota) in human metabolism and obesity is being increasingly recognized. The goal of this article was to provide a commentary on the clinical usefulness of these data. METHODS:We performed a review of the currently available articles on PubMed. FINDIN...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审


    authors: van Olden C,Groen AK,Nieuwdorp M

    更新日期:2015-06-01 00:00:00

  • Topiramate monotherapy in the treatment of newly or recently diagnosed epilepsy.

    abstract:BACKGROUND:The efficacy of topiramate (TPM) as an adjunctive treatment for epilepsy has been established in placebo-controlled clinical trials. Clinical trials of antiepileptic monotherapy usually evaluate low and high doses of study drug or compare study drug with another active agent. OBJECTIVE:This article reviews ...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审


    authors: Ben-Menachem E,Sander JW,Stefan H,Schwalen S,Schäuble B

    更新日期:2008-07-01 00:00:00

  • Patient preference for once-weekly alendronate 70 mg versus once-daily alendronate 10 mg: a multicenter, randomized, open-label, crossover study.

    abstract:BACKGROUND:Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation. OBJECTIVES:This study aimed to determine patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the p...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Simon JA,Lewiecki EM,Smith ME,Petruschke RA,Wang L,Palmisano JJ

    更新日期:2002-11-01 00:00:00

  • Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation.

    abstract:BACKGROUND:Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). OBJECTIVE:The objective of this study was to evaluate the cost-effect...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章


    authors: Lip GY,Kongnakorn T,Phatak H,Kuznik A,Lanitis T,Liu LZ,Iloeje U,Hernandez L,Dorian P

    更新日期:2014-02-01 00:00:00

  • Nizatidine for the treatment of pediatric gastroesophageal reflux symptoms: an open-label, multiple-dose, randomized, multicenter clinical trial in 210 children.

    abstract:BACKGROUND:Gastroesophageal reflux disease (GERD), which is reflux that produces damage or troubling symptoms, afflicts approximately 7% of infants and children to the extent that administration of physician-directed pharmacotherapy is warranted. OBJECTIVE:This study was designed in conjunction with the US Food and Dr...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Orenstein SR,Gremse DA,Pantaleon CD,Kling DF,Rotenberg KS

    更新日期:2005-04-01 00:00:00