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A Nurse-Led, Patient-Centred Mitoxantrone Service in Neurology

Source: British Journal of Nursing

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous

system for which there is no known cure. There are licensed treatments

available to influence the disease course, but for a small group of patients,

progression of the disease may continue at an alarming rate. Mitoxantrone, a

cytotoxic agent normally used in the treatment of cancer, has been shown to

reduce disease activity in patients who have this more aggressive form of MS.

However, the immunosuppressive action and side-effect profile of

mitoxantrone mean that this drug should be used with caution. This article

describes a MS nurse-led initiative where an evidence-based, integrated care

pathway was designed to ensure a safe, high-quality service provision for this

select patient group.

Key words: Multiple sclerosis * Care plans and planning * Multidisciplinary

teams

Multiple sclerosis (MS) is an incurble autoimmune-mediated, nflammatory

disease of the cenral nervous system that usually presents -with a history of

acute onset of neurological symptoms (relapses), or progressive neurological

impairment (Compston and Coles, 2002). The cause is unknown, although it

is believed that a non-specific viral infection may trigger an autoimmune

reaction in a genetically susceptible individual (Compston, 1997). The

disease process effects myelinated nerve fibres, such as the optic nerve and

the white matter tracts of the brain and spinal cord. This may lead to a variety

of symptoms, e.g. visual disturbances, weakness and sensory symptoms

(Toosy and , 2000).

It is estimated that between 52000 and 62000 people have MS in the UK

(National Institute for Clinical Excellence (NICE), 2003) and around 2.5

million people are affected " worldwide (Compston and Coles, 2002). MS

typically presents between 20 and 40 years of age. Females are more

susceptible than males by a factor that approaches 2:1 (Mc, 1998).

Race and geography also affect susceptibility to the disease (Sadovnick and

Ebers, 1993).

MS nurses are able to empower those affected by MS by providing

information, support and advice about the condition from time of diagnosis

and throughout the disease spectrum. The MS nurse is pivotal in providing a

greater understanding of the condition, and by adapting a holistic,

collaborative and coordinated approach can help individuals, where possible,

reach their goals of self- management (UK Multiple Sclerosis Specialist Nurse

Association et al, 2001).

Disease-modifying drugs in MS

There are four disease-modifying drugs (DMDs) available to patients with MS.

The double-blind placebo-controlled trials of these drugs have demonstrated

a reduction in the severity and frequency of relapse rate, by approximately

30%, in patients with relapsing/remitting MS (RRMS) or in patients with

secondary progressive MS (SPMS) with superimposed relapses (Association

of British Neurologists, 2001). The drugs that are available include interferon

beta (Avonex, Betaferon, Rebif) and glatiramer acetate (Copaxone).

Currently, DMDs are the only form of licensed treatments in the UK that

influence the disease course. Unfortunately for some MS patients, these

treatments are not effective and rapid deterioration in their condition

continues. Many centres are now using a potent cytotoxic preparation called

mitoxantrone for patients who have failed DMDs or have a more aggressive

form of the disease.

The role of immunosuppressants in MS

MS immunosuppressant therapies focus on the modulation or suppression of

the immune system, which underscores the major role the inflammatory

response plays in the pathology of the disease (Porter et al, 2004).

Immunosuppressants used in MS include: azathioprine, ciclosporin,

mcthotrexate and mitoxantrone (Toosy and , 2000). These drugs

may be used in isolation or in combination; however, mitoxantrone is fast

becoming the first-line cytotoxic drug of choice in many centres (personal

communication).

Mitoxantrone (Novantrone) is an antineoplastic agent, which exerts potent

immunomodulating effects to the immune system including suppression of B

cell immunity and reduction of T cell number (Dalton, 1999). The

recommended dose is 12 mg/m^sup 2^ administered by intravenous infusion

trimonthly (Hartung et al, 2002) or 20mg administered monthly for 6 months

(Edan et al, 1997). Mitoxantrone has the potential to cause cardiotoxicity and

therefore the total cumulative dose should not exceed 140 mg/m^sup 2^ of

mitoxantrone (Ghalie et al, 2002). It is licensed for the use in MS in the USA,

but as yet has not been licensed in the UK.

Clinical trial results

To date there have been three important pivotal trials carried out to measure

the effectiveness and safety of mitoxantrone in patients with worsening MS. In

1997, Millefiorini et al carried out a phase 11 placebo-controlled trial which

involved 51 patients with relapsing/remitting MS. Patients were randomized to

either receive mitoxantrone 8 mg/m^sup 2^ or placebo for 1 year. Results

showed a significant reduction in the annual number of exacerbations and a

significant increase in the proportion of exacerbation-free patients in the

mitoxantrone group compared with the placebo group.

In the same year, a collaboration of French neurologists (Edan et al, 1997)

undertook another phase 11 study with 42 patients with RRMS and SPMS.

The patients were randomized to either receive mitoxantrone 20 mg and

methylpreeinisolone 1 g or methyprednisolone 1 g alone. Results showed an

improvement in Expanded Disability Status Score (EDSS) (Kurtzke, 1983) by

one point from baseline and also a reduction in relapse rates. The EDSS is a

quantitative clinical scale of neurological impairment ranging from 1-10.

Increasing increments on the scale represent increasing disability (Toosy and

, 2000).

More recently, Hartung et al (2002) conducted a larger phase 111 controlled

randomized double-blind study of 194 patients with RRvMS and SPMS.

Patients were randomly assigned to receive placebo mitoxantrone 5mg/m^

sup 2^ or mitoxantrone 12mg/m^sup 2^. A total number of 188 patients were

able to be assessed at 24 months. At 24 months, the mitroxantrone group

compared with the placebo group experienced benefits on the EDSS and a

number of outcome measures. This study suggests that mitoxantrone was

well tolerated and reduced progression of disability and clinical

exacerbations.

Side-effect profile

As a potent cyctoxic drug, mitoxantrone, like any chemotherapy agent, has the

potential to cause harmful side-effects. The most common side-effects

reported throughout the three pivotal trials included: myelosuppression,

nausea and vomiting, alopecia, amenorrhoea, and urinary and upper

respiratory tract infection (Edan et al, 1997; Millefiorini et a), 1997; Hartung

et

al, 2002). Mitoxantrone has also been associated with cardiotoxicity (Ghalie

et al, 2002) and can cause infertility for both males and females

(Cancerl)acup, 2000).

Introduction of mitoxantrone in a neurological environment

The immunosuppressive action and side-effect profile of mitoxantrone means

that this drug should be used with caution. At a large teaching hospital in

London, mitoxantrone was introduced within a haphazard medical model. A

nurse-led audit initiative of the first cohort of treated patients identified a

number of complications including neutropenia, and severe urinary tract and

skin infections among this patient group.The MS nursing team raised

concerns regarding safe practice and highlighted a number of areas that

needed to be explored within a clinical governance framework. Examples of

the areas of concern include: lack of coordination; lack of named, trained

staff;

lack of advice on potential infertility; lack of pregnancy screening; and poor

documentation.

It is recognized that as a clinical expert, the MS specialist nurse must be able

to: identify areas for improvements; lead service development; and design

care pathways appropriate to people with MS across the trajectory of the

disease course (UK Multiple Sclerosis Specialist Nurse Association et al,

2001). In an effort to ensure best practice, the MS nursing team at the National

Hospital for Neurology and Neurosurgery, University College London

Hospitals (UCLH), completed a literature search and spent time discussing

the use of mitoxantrone with colleagues in the cancer team.

In discussion, the option of the cancer team delivering mitoxantrone in

isolation of the MS services and the option of mitoxantrone being delivered by

the neurology team following specialist education and training were explored.

In any clinical situation the benefits of treatments must be weighed against the

risks. When the risks of therapy include irreversible cardiac damage,

infertility,

and infection, the decision to treat and the process of so doing becomes

considerably more complex. In an effort to deliver care in a holistic rather

than

task-oriented framework a decision was made that these complicated MS

patients would receive this treatment in a neurological setting following staff

training and support from cancer services.

Table 1. Standards of care adapted from Department of Health (2000)

Introducing standards

In order to design a safe service, standards of care need to be formulated. At

the authors' hospital, the MS nursing team adopted the standards from the

Manual of Cancer Service Standards (Department of Hea\lth, 2000) to reflect

safe practice within a neurological setting (Table T). Although these standards

have helped create a framework for safe drug administration they have also

highlighted the need for a more patient-centred, coordinated approach to care

delivery in order to improve the quality of the service offered. A

multidisciplinary integrated care pathway (ICP) was agreed to be the most

appropriate way of improving the quality of the service.

Integrated care pathways

Middle-ton et al (2001) state that: 'An integrated care pathway (ICP) is a

multidisciplinary outline of anticipated care, placed in an appropriate

timeframe, to help a patient with a specific condition or set of symptoms move

progressively through a clinical experience to positive outcomes.' Kitchiner

and Bundred (1996) suggest that ICPs use multidisciplinary guidelines to

develop and implement clinical plans, which represent current local best

practice for specific conditions. ICPs also incorporate national guidelines,

evidence-based practice and benchmarking. Pathways are devised into time

intervals during which specific goals are expected, together with guidance on

the optimal timing of appropriate investigations, advice on side-effect

management and treatment options.

The ICP forms part of the clinical record, and in some cases it replaces other

forms of documentation, such as nursing care plans (UCLH, 2003). While

patients' progress follows the pathway, the appropriate health professional

signs for the care he/she has delivered. If the patient's care or progress

varies

from the pathway it k recorded as a variance, together with the reason and the

action that has been taken.

Members of the team can choose to deviate from the pathway but this must be

clinically justified, e.g. deterioration in the patient's condition or

intolerable

side-effects (Kitchiner and Hundred, 1996). This encourages staff to adhere to

the guidelines specified on the pathway, thus reducing variations in the care

provided. ICPs allow innovative and creative ways of improving quality of

care, allowing quality assurance to flourish. Onslow et al (2003) recognize

that NHS trusts are increasingly requiring ICPs to be developed for reasons of

finance, bed management and to meet the requirements of clinical

governance.

The main strength of the mitoxantrone multidisciplinary ICP is that it is

patient

focused as the delivery of care focuses on the patient's journey, thus

improving coordination and consistency. By having explicit evidence-based

standards, unnecessary variations to care are reduced. It also allows the

clinical team to identify strengths and weaknesses within the area of practice,

and ensures that clinical guidelines and evidence are incorporated into

everyday practice (Middelton et al, 2001).The mitoxantrone ICP also provides

a framework to allow prospective audit against local and national MS

guidelines (NICE, 2003). NICE guidelines state that mitoxantrone should only

be used in the following circumstances: after full discussion and consideration

of all the risks; with formal evaluation, preferably in a randomized or other

prospective study; and by an expert in the use of these medicines in MS.

The lead clinician assesses patients against predetermined eligibility criteria,

as approved by the trust pharmaceutical board. A complete neurological

examination, including a review of functional systems and an EDSS, is

completed. On completion, patients are provided with an information booklet,

which provides evidence-based information outlining the risks and benefits of

the treatment and side-effect profile to help make an informed decision about

proceeding with treatment. Patients who wish to proceed arc referred to the

nurse-led preinfusion assessment clinic, which is the starting point of the

mitoxantrone ICR

The clinical nurse specialist (CNS) plays an important role at this stage, by

gaining a baseline measure of the impact of MS on each individual using a

new patient-based outcome measure known as the Multiple Sclerosis Impact

Scale (MSIS-29) (Hobart et al, 2001). The MSIS-29 is an instrument which

measures the physical (20 items) and psychological (9 items) impact of MS. In

addition, the patient's general health including history of infections, cardiac

disease, tissue viability, and understanding of the treatment trial results and

potential side-effects are all assessed. The CNS also orders baseline

investigations including blood screening, electrocardiogram and X-rays while

discussing options for sperm or egg donation as appropriate. In addition,

referrals to other mulodisciplinary team members as necessary are made and

the GP is informed of the treatment plan.

This screening clinic allows the nurse to make vital nursing assessments of

patients' physical, psychosocial, emotional and social functioning. The CNS

provides education to the patients, checks their level of understanding and

gains insight into their expectations from therapy as well as providing

answers to their many questions. Following this clinic, a follow-up telephone

call is made by the CNS to inform patients of their test results and to check

that they wish to proceed. If patients do not wish to proceed they return to the

care of their neurologist to discuss other treatment options and management.

In order to ensure that the MS nurse specialists up-skilled rather than de-

skilled staff on the designated unit a training programme was designed in

collaboration -with the cancer team. The nursing staff on the designated unit

undertook training specific to the administration of mitoxantrone in MS. The

unit nurses were highly motivated and competent and volunteered to become

key workers taking responsibility for the overall delivery of treatment and

coordination of care during each individual's treatment cycle.

Patients who wish to proceed with treatment are therefore given the contact

details of a key nurse from the designated infusion unit who arranges a

suitable date and time for admission. The drug is administered over six cycles

in accordance with the clinical care guidelines of the ICP which include

protocols for communication with the GP and referral back to the CNS-MS and

neurology team.

Patients are provided with a mitoxantrone patient handheld record, which

records information that other health professionals can access should the

patient present or if complications arise. Once the final treatment has been

completed the patients return to the CNS-MS for an overall review of their

health, a summary of their treatment, and remeasurement of their individual

impact of MS scale. Patients are then referred back to the neurologist for long-

term neurological management.

Summary

The delivery of mitoxantrone in a neurological setting requires a sound

infrastructure based on evidence-based practice within a clinical governance

framework. Nurse specialists are well placed to learn from other specialist

colleagues to ensure that practice is safe and patient centred. The

introduction of a nurse-led multidisciplinary mitoxantrone ICP at the National

Hospital for Neurology and Neurosurgery, UCLH, is an example of nursing

collaboration and leadership where vision, courage, reality and ethics were

balanced to create a service that directly improves the patient experience and

quality of care delivered.

With special thanks to our colleagues: Kay Eaton (Nurse Consultant/Lead

Cancer Nurse), (Pharmacist), Ellen (Ward Sister),

Professor Alan (Neurologist), Or Gavin Giovannoni (Neurologist),

ana Liz Keenan CNS-MS for their support in assisting with this project.

KEY POINTS

* In aggressive forms of multiple sclerosis (MS), a cyctoxic drug called

mitoxantrone has been shown to reduce disease activity.

* Collaborative working with cancer colleagues is imperative in setting up

safe mitoxantrone services.

* Integrated care pathways designed within the clinical governance

framework can standardize practice and ensure positive patient outcomes.

* The multiple sclerosis (MS) nurse specialist can play a pivotal role in the

establishment and delivery of MS services.

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oii is Clinical Nurse Specialist and Bernadette Porter is Nurse

Consultant Multiple Sclerosis, The National Hospital for Neurology and

Ncurosurgery, University College London Hospitals, London

This article was the winner of the Multiple Sclerosis Award at the 2004 BJN

Clinical Practice Awards. The award was sponsored by Serono

Copyright Mark Publishing Ltd. Sep 23-Oct 13, 2004

   

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