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Multiple Sclerosis
The Effect of Tolerability on Adherence and Quality of Life
Improving Tolerability as a Means of
For a patient to maintain adherence and reap the complete benefits of
their disease-modifying therapy, their treatment must be tolerable. MS
Ameliorating Drug Therapy
patients often experience headaches, and headaches related to
Presenting data from the Rebif New Formulation Study, Dr William treatment with interferon beta that were independent of flu-like
Camus (France) spoke of the improvements in immunogenicity, symptoms have recently been found to be more frequent than
safety and tolerability. The objective of the phase IIIb single-arm, previously reported. Although not a contraindication to therapy with
open-label Rebif New Formulation (RNF) Study was to evaluate the interferon beta, physicians are suggested to monitor patients for
product’s safety and immunogenicity in relapsing–remitting headaches and to adjust therapy if the frequency increases.
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multiple sclerosis (RRMS). Enrolment criteria required patients aged
18–60 years of age with expanded disability status scale (EDSS) The BENEFIT studies have demonstrated good tolerability to interferon
<6.0 to be naïve to treatment with interferon beta. Patients self- beta-1b in patients with CIS, with a high adherence rate after three years
injected RNF at 44mcg three times a week over a period of two (>73.3%) and a large proportion (>89.3%) of patients choosing to
years. Patients treated with RNF had a lower rate of neutralising continue therapy in the follow-up study.
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A comparison of tolerability
antibodies compared with data from the EVIDENCE and REGARD between interferon beta-1b 250mcg and glatiramer acetate in the
studies, indicative of an improved immunogenical profile, and also BEYOND study showed that patients treated with interferon were more
experienced a significant reduction in annualised relapse rate.
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likely to experience flu-like symptoms, although the incidence of this
adverse effect decreased with time. In contrast, injection-site reactions
Focusing on adverse events, there was a nearly three-fold reduction were commonly reported by patients receiving glatiramer acetate.
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in injection-site reactions compared with previous studies, at
30.8% compared with 85.8 and 41.2% in the EVIDENCE and The new formulation of interferon beta-1a (Rebif new formulation [RNF]),
REGARD studies, respectively. Surprisingly, though, flu-like produced without foetal bovine serum and human serum albumin, has
symptoms were much higher, at 71.5% versus 49.0 and 36.0% in shown reduced immunogenicity compared with the current formulation in
the EVIDENCE and REGARD studies, respectively,
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which has patients with relapsing MS.
59,60
The incidence of serious adverse events was
prompted researchers to further analyse this issue through the similar to that seen in data from the Evidence of Interferon Dose-response:
Transition to Rebif New Formulation (TRANSFER) study. ■ European North American Comparative Efficacy (EVIDENCE) and REGARD
studies, although patients were more likely to have flu-like symptoms with
RNF. However, RNF had fewer patient-reported injection-site reactions and
Gd+ lesions or T1 black holes or brain volume.
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A similarly high feelings of depression. The overall safety and tolerability profile of RNF
proportion of patients in each arm were free from disease activity.
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relative to the current formulation of interferon beta-1a is proposed to
However, T2 lesion volume change and cumulative volume were lower in influence treatment adherence.
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groups using interferon beta-1b compared with glatiramer acetate,
suggesting that there may be different effects on the overall disease As with any chronic life-long disease, adherence to drug therapy is a
burden depending on treatment.
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major determinant of the success of the disease-modifying therapy, and
this concept is no different in MS. Adherence and relapse rate are closely
Natalizumab has been recommended as second-line therapy for patients associated: one study has shown that patients who refused to adhere to
who continue to progress while receiving the first-line disease-modifying treatment for over 90 days face a significantly increased risk of severe MS
therapies. Patients with relapsing MS in the Natalizumab Safety and relapse compared with patients with shorter or no gaps in drug-
Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) or Safety modifying treatment.
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and Efficacy of Natalizumab in Combination with Interferon Beta-1a in
Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) trials were Studies have also shown that adherence varies depending on the drug in
monitored for disease activity, and researchers found that natalizumab, question. Adherence in the BEYOND trial was high in all groups, but a
whether as a monotherapy or in combination with interferon beta-1a, slightly higher number of patients treated with interferon beta-1b
yielded a significantly higher proportion of disease-activity-free patients 250mcg (82%) saw the study through to completion compared with
compared with placebo over two years based on both clinical and MRI those treated with high-dose interferon beta-1b 500mcg (73%) or
data measures.
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Although approved for use as in RRMS, natalizumab is glatiramer acetate (78%).
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associated with fatigue and allergic reactions, as well as potentially fatal
adverse events such as anaphylactic shock, progressive multifocal Certainly, the results from clinical trials with respect to adherence are an
leukoencephalopathy, infections and clinically significant liver damage. area to be considered by physicians when prescribing medications for
These safety issues and the lack of information regarding long-term use patients, and the subject of adherence is an important one, as drug
has led to reservations over using the drug outside of clinical research. compliance is closely linked to the patient’s quality of life – the efficacy of
a drug is irrelevant if patients exhibit poor compliance, for example, due
Although mitoxantrone has been suggested for aggressive forms of MS, it to bad adverse effects or low tolerance, which ultimately leads to disease
has also been associated with a risk of oncogenesis. The prevalence of acute progression and poor patient outcome. However, quality of life is not
myeloid leukaemia (AML) is significantly increased in MS patients who solely dependent on drug use and compliance: one study assessed a
receive mitoxantrone treatment, and appears to occur in younger patients. cohort of Polish subjects with MS to determine the most important factors
No apparent correlation was found between previous MS treatments and affecting quality of life and found depression, level of disability, fatigue
cumulative mitoxantrone dose with the risk of developing AML.
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and marital status to be the strongest predictors of quality of life.
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In the
82 EUROPEAN NEUROLOGICAL REVIEW
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