Review
Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: An Australian and New Zealand perspective Part 3 Treatment practicalities and recommendations

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Abstract

In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high.

Introduction

In this third and final part of our review we look at the many factors that can influence the choice of treatment for individual people with multiple sclerosis (MS). These include specific matters relating to women with MS and adverse effect profiles. We provide practical advice on how to manage the common and rarer, but important, adverse effects that are seen with these therapies. We then go on to make specific recommendations with regards to the use of disease modifying therapy (DMT) in MS.

Section snippets

Breakthrough disease and switching therapy

Studies of outcome in patients on therapy clearly indicate a worse prognosis for patients experiencing further disease activity in the form of clinical relapses [1], [2], worsening disability [3] or new MRI activity [2], [4]. This has led to the concepts of “freedom from disease activity” [5] and “breakthrough disease” [6] or “suboptimal response” [7] whilst on therapy. The degree to which new disease activity should prompt a reconsideration of treatment is far from black and white, but an

Pregnancy and breast feeding

No treatment for MS is currently listed as being safe for use in pregnancy or breast feeding (Table 2 in Part 1 Historical and established therapies of this review) and the general recommendation for all is that treatment should be discontinued prior to conception or when a woman unexpectedly discovers that she is pregnant. A recent systematic review of reproductive issues in MS treatment came to the same conclusion based on currently available published data [34]. However, as summarised in

Monitoring and antibody testing

Pre-treatment, peri-treatment and continuous monitoring recommendations for each of the agents is summarised in Table 4. Testing for neutralising antibodies is available for β-interferon and natalizumab. The presence of persistent significantly elevated titres of these antibodies is consistent with non-bioavailability of the drug and therefore loss of efficacy. However, the practical relevance of testing for these antibodies is questionable as the only setting in which they would be requested

Management of adverse events

A summary of the frequency and severity of adverse events for current and emerging therapies is provided in Table 5.

Recommendations

In patients presenting with clinically isolated syndrome, treatment with an injectable DMT should be considered (class I evidence). Factors that impact on this decision will include certainty of diagnosis, balance of prognostic factors (Table 6) [118] and patient preference. In patients with significant motor or brainstem presentations where there is limited recovery, positive oligoclonal bands in cerebrospinal fluid (not seen in serum) and convincing MRI features supportive of a diagnosis of

Conclusions

MS in its active (relapsing) stage should now be regarded as a treatable disease. There are a range of treatments that include highly effective therapies which can significantly reduce the frequency of relapses and the extent of inflammatory lesions on MRI. Good control of MS disease activity should be the goal in all patients. Unfortunately, no therapies are available to prevent progressive MS or reverse late stage disability. However, reducing disease activity early may reduce the number of

Conflicts of Interest/Disclosures

MHB has received honoraria for participation in advisory boards and travel sponsorship from Novartis, BioCSL, Genzyme and Biogen Idec.

BJB has received honoraria as an advisory board member for GlaxoSmithKline, Biogen Idec, ViiV Healthcare and Merck Serono, has received speaker honoraria from ViiV Healthcare, Boehringer Ingelheim, Abbott, Abbvie, and Biogen Idec; has received travel sponsorship from Abbott and Viiv Healthcare, and has received research support funding from EI Lilly,

Acknowledgements

We are grateful to Bayer, Biogen-Idec, CSL Ltd, Genzyme, Merck Serono and Novartis for providing pregnancy outcomes data.

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