Multiple Sclerosis
Figure 3: Combined Improvement in Walking Speed Produced by Dalfampridine or Placebo in Three Pivotal Clinical Trials (MS-F202, MS-F203 and MS-F204)
100
80 60
40 20 0
p<0.001 80.2
64.1
p<0.001 54.1
32.5
p<0.001 31.5
13.1
p<0.001 15.5
3.8
34% regarding improvement in functional status before the initiation of therapy. Education reduced these figures, but following this education, expectations remained high and were significantly related to the discontinuation of therapy within six months.47
In addition, depression
and flu-like symptoms were also found to be associated with the discontinuation of therapy.
p=0.025 2.5 6.6
p=0.433 p=0.717 1.72.8
0.81.5
≥0% ≥10% ≥20% ≥30% ≥40% ≥50% ≥60% Average percent increase in walking speed from baseline
Placebo (n=237) Dalfampridine 10mg twice daily (n=394)
Figure 4: Strategy for Treating Walking Impairment in Multiple Sclerosis Patients with Dalfampridine
Patients with all types of MS and difficulty walking
Previous studies have shown that managing patient expectations and maintaining good communications between healthcare providers and patients can improve adherence to DMT and, consequently, improve outcomes.48,49
predictors of adherence to DMT.50
Self-efficacy, self-esteem, and hope have been reported as Therefore it is important to maintain
an open and trusting relationship between patients and healthcare providers. Understanding of and empathy for the patient’s fears, expectations, and health beliefs are crucial. Healthcare providers should give patients the necessary information for them to make informed decisions regarding the available treatment options and should monitor and counsel them throughout treatment. In the case of dalfampridine, patients could be prescribed this drug for a number of years; therefore it will be critical to ensure that only those patients who respond to treatment and tolerate it well receive longer-term dalfampridine therapy.
Counsel patients on likelihood of
response, discuss and establish realistic patient expectations, explain most common adverse events
Treat with dalfampridine 10mg twice daily
Improvement in walking (T25FW, MSWS-12 or other test), good tolerability
Small
improvement in walking (T25FW, MSWS-12 or other test), good tolerability
Improvement in walking (T25FW, MSWS-12 or other test), poor tolerability
Small
improvement in walking (T25FW, MSWS-12 or other test), poor tolerability
Continue dalfampridine treatment and monitoring
Stop dalfampridine treatment – use alternative therapy e.g. physiotherapy
In the case of a patient receiving dalfampridine who has very limited or no perceived improvement in walking ability but has good tolerability, one strategy may be to discontinue the drug and observe whether the patient subsequently becomes aware that the drug was more effective than they realized. MS = multiple sclerosis; MSWS-12 = 12-Item Multiple Sclerosis Walking Scale; T25FW = Timed 25-Foot Walk.
significant benefits to some patients but not all. A substantial proportion of patients may show little or no improvement in walking and a minority may suffer adverse effects that they can find difficult to tolerate. It is very important that prescribers are aware of these limitations and explain them to patients before they begin treatment.
Unrealistic expectations of disease modifying therapies (DMTs) have been previously shown to result in poor treatment adherence, and a perceived lack of efficacy accounts for 30 to 52% of discontinuations of DMTs.45,46 Among patients receiving IFNβ therapy in one study, 57% of patients had unrealistic expectations regarding reduction in attack rate and
80
Conclusion and Future Developments Dalfampridine has been shown in clinical trials to improve walking ability in MS and therefore has the potential to increase the function and QOL of many patients with MS. It remains to be determined how to identify those most likely to respond to treatment. Since recent clinical trials demonstrate that approximately one-third of patients with all disease types and disability ranges show benefit from dalfampridine treatment, patient education programs should include this information. These programs should help to limit unrealistic expectations of treatment effects and guide patients to understand the chances of treatment efficacy and the risk of adverse events. Such strategies are also likely to help limit dalfampridine treatment to those patients who may potentially respond to the medication. Patients receiving dalfampridine should be encouraged to maintain frequent communication with their healthcare provider. Guidelines should be established to describe the best practice when using dalfampridine to treat walking impairment in MS and to recommend the best treatment practice for both responders and non-responders to dalfampridine. A potential strategy for guidance for the use of dalfampridine, integrating patient counseling stages, and measurement of walking ability is outlined in Figure 4.
The increased incidence of seizures has been of concern in the clinical development of dalfampridine. However, given the low frequency of seizures observed so far in clinical trials, it is impossible to draw firm conclusions on the exposure-response relationship. At the intended dose of 10mg twice daily, the data suggest that the risk is low. This emphasizes the critical need to educate practitioners and patients on the critical importance of using only the recommended dose of dalfampridine. A growing body of evidence suggests that the combination of pharmacological management and rehabilitation may result in better outcomes than one therapeutic intervention alone.51 Dalfampridine should be part of a wellness program including a DMT, exercise, time and stress management, diet, sleep, and regular visits to the healthcare provider.2
n US NEUROLOGY
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