RELAPSE MANAGEMENT Pauline Shaw MS Nurse Specialist 25 th June 2010
AIMS OF SESSION Relapsing/Remitting MS Definition of relapse/relapse rate Relapse Management NICE Guidelines Regional Clinical Guidelines
RRMS 80 85% of new cases will present with RRMS 40 75% RRMS will go on to develop SPMS Most widely recognised type of MS RRMS varies greatly in severity in individuals Frequent relapses at the onset of disease are associated with poorer prognosis (Weinshenker 1995)
Clinical course of RRMS Variable, intermittent disease course Attacks or exacerbation of symptoms (relapses) Followed by full or partial recovery (remission) Disability accumulation due to incomplete recovery from relapses
Relapse Episode of acute or sub acute neurological symptoms of variable severity Rapid appearance of new symptoms or reappearance of old over 1 2 weeks Relapse symptoms last more than 24 hours in the context of normal body temperature Typically 2 6 weeks May persist for 6 months or longer Annual relapse rate initially averages 2 2.5 (Barnes 2000) gradually falling as the years progress
Remission Can last any length of time Spontaneous recovery generally within 8 12 weeks Degree of recovery unpredictable and variable May be complete (early in disease) or incomplete with residual disability
Relapse trigger factors? Stress Stress includes emotional stress, trauma, and medical interventions NICE recommend that if a person with MS needs surgery for any reason then the surgery should go ahead Injury / trauma Studies indicate that relapse is no more likely to happen (Thompson 2002)
Relapse trigger factors? Hormonal changes following child birth No evidence that pregnancy itself influences the overall course of MS over time Risk of relapse decreases during pregnancy, in the third trimester relapse is reduced by 60% (Thompson 2002) with same increase in relapse 3 months postpartum Vaccinations A number of studies are inconclusive but Flu vaccine is now confirmed safe (NICE 2003)
Confirmation of new relapse Establish: presence of new symptoms re occurrence of old symptoms for longer than 24hours Exclude pseudo exacerbating factors: Infection test urine menstrual cycle stress Confirm a period of 30 days from end of any previous relapse
Should You Treat if UTI Suspected? Steroids usually delayed if UTI suspected in local service UCL study Study of 249 relapsing MS patients If dipstick +ve abx started at same time as MP If culture neg then abx stopped Results UTI in 11% 67 patients commenced on abx with negative culture 7 patients negative dipstick but positive culture
Should You Treat if UTI Suspected?
Treatment of relapses Assessment Take history Confirm relapse Determine severity, functional disability / loss Exclude infection Medication Supportive therapy Physiotherapy; occupational therapy; counselling Care package Hospital admission for severe relapse
Relapse Management Decision Aids NICE Guidelines / Scottish Guidelines / Cochrane Review / EFNS Guidelines/Local Guidelines http://www.pathways.scot.nhs.uk/neurology/neurol%20ms%2023sep05.ht m
Relapse management NICE Recommendations: Any individual who experiences an acute episode sufficient to cause distressing symptoms or an increased limitation on activities should be offered a course of high dose corticosteroids intravenous methylprednisolone 500mg 1g for 3 to 5 days high dose methylprednisolone 500mg 2g daily for 3 to 5 days An individual should be given a clear explanation of the risks and benefits involved in taking corticosteroids Prolonged and frequent courses should not be used NICE MS Guidelines. 2004 National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care
Steroids for relapses Anti inflammatory effect Suppress immune system Stabilise blood brain barrier Thought to speed recovery BUT do not influence degree of recovery or long term progression of disease Side effects minor but include weight gain, acne, cataracts, osteoporosis and diabetes The NICE Guideline recommends courses of steroids be limited to a maximum of three times a year NICE MS Guidelines. 2004 National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care
Anti inflammatory effect Reduce inflammatory responses by inducing several effects on the immune system Inhibit lymphocyte proliferation and cell mediated immune response Decrease circulating T helper cells, eosinophils & monocytes Down regulate cytokine gene expression Suppress synthesis of prostaglandins & leukotrienes Block activation of T cells by IL 1 Inhibit expression of class II histocompatibility antigens on macrophage surface
Corticosteroids side effects Common : Oedema Raised glucose GI symptoms Metallic taste Anxiety / depression Reddening of face Altered sleep Usually well tolerated. Most SE transient Less common Infection HT Avascular necrosis Pancreatitis Herpes simplex Zoster Seizures Weight gain Anaphylaxis
Compared 1g MP iv with 1250mg prednisone orally (oral MP not available in Canada) No difference in bioavailability between steroids administered either iv or orally (approx 80%) Oral treatment is preferred by most patients, is cheaper, more convenient and has equivalent gastric safety profile
Forty patients with MS randomized to receive either 1 g/day for 5 days of omp (20 patients) or 1 g/day for 5 days of IV MP (20 patients) Expanded Disability Status Scale (EDSS) and brain MRI (dual echo and postcontrast T1 weighted scans) were assessed at baseline and at weeks 1 and 4 The 2 groups showed a reduction of Gd enhancing lesions over time with a non inferiority effect between the 2 routes of administration at week 1. Both groups showed an improvement of EDSS over time (p 0.001) without between group difference at week 4. Both treatments were well tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms.
MS Relapse Guidelines NICE Guidelines (2003)
Innovation Regional MS relapse guidelines developed (2005) provide clear step by step guidance for treatment with oral steroids in a form that can be faxed to GP / pharmacy Avoids need to admit patients to hospital for intravenous steroids in the majority of cases PwMS receive treatment earlier and significant cost savings
Current Guidelines Treat only if relapse is distressing relapses or limiting activities Check for UTI (Multistix for protein / nitrites) and delay treatment if present Patient Information Sheet Oral Prednisolone 500mg x 5/7 od (taken in the morning with food) PPI if PUD / gastritis or concurrent aspirin / warfarin Follow up after 6 weeks Ennis M et al. BJNN 2008;4(6):266-271
Published December 2005 Short term, high dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation) Intravenous or oral methylprednisolone in a dose of at least 500 mg daily for 5 days should be considered for treatment of relapses (level A recommendation). Treatment with IV methylprednisolone (1 g once daily for 3 days) should be considered as an alternative treatment (good practice point; Multiple Sclerosis Therapy Consensus Group, 2004) There is no evidence of major differences in the efficacy of methylprednisolone treatment given IV or orally in terms of clinical efficacy or side effects, but prolonged, oral treatment may possibly be associated with a higher prevalence of side effects
EFNS MS Relapse Guidelines Treatment Failure In patients who fail to respond to treatment with MP in the dose ranges used in placebo controlled trials higher doses should be considered (up to 2g / day for 5 days) (level C recommendation) [Multiple Sclerosis Therapy Consensus Group. J Neurol 2005;251:1329 1339] If patients do not respond to MP, one third may respond to PLEx Intense, interdisciplinary rehabilitation programme should be considered after treatment with MP No evidence to support ivig or Natalizumab