Muscular symptoms



Spasticity: Oh, what a drag!     
By Sarah Johnson, Pharm.D.
Originally published in eMS News November 25, 2009 Approximately 70% of people with multiple sclerosis (MS) experience difficulty due to spasticity. The legs are generally more affected than other muscles and patients may experience spasticity greater on one side of the body than the other. Signs of spasticity include stiffness, tightness or involuntary muscle spasms. Spasticity can make mobility difficult, interrupt sleep, as well as be uncomfortable and painful. Severe spasticity left untreated can lead to restriction of movement in the joints, pain and skin breakdown which may lead to pressure ulcers and infection. The overall result is a significant reduction in quality of life.

Fortunately, there are treatments available for the management of spasticity. These include physical therapy and drug therapy. There are several drugs that are approved for the treatment of spasticity. The agents that are most commonly prescribed include baclofen and tizanidine. Both of these agents are effective for treating spasticity but they must be taken several times a day and intolerable side effects may limit their use for some patients. Baclofen was approved by the Food and Drug Administration in 1977 for the treatment of spasticity and is still widely used. A new extended-release (ER) version of baclofen, referred to as IPX056 developed by IMPAX Pharmaceuticals, is now being tested in a multi-center clinical trial. The drug could have a significant impact on the treatment of spasticity and patient quality of life.

IPX056 is designed so that the drug is released slowly over time which allows for a steady concentration in the system. The advantage to this formulation is that patients may be able to take fewer pills per day without a significant change in their spasticity. Currently, some patients may take the immediate release formulation of baclofen up to four times a day for management of their spasticity. Remembering to take a pill four times a day can be difficult and cumbersome for some patients. If they forget to take their medication or don’t have it with them then they may experience breakthrough of spasticity. Additionally, patients may awaken during the night due to spasticity caused by the medication wearing off during the night. Interruption of the sleep cycle can contribute to fatigue and cognitive dysfunction. IPX056 could be beneficial by maintaining a consistent dose of baclofen throughout the day and night so that the patient doesn’t experience disruptions due to spasticity during the day or night. Another advantage of IPX056 may be a reduction in side effects. Since the medication is released slowly over time, there may be less variability in the amount of drug that is in the body. This may improve the tolerability of the medication. Patients who are unable to take the immediate release version of baclofen due to intolerable side effects may benefit from the extended release version. The purpose of the current clinical trial is to investigate the therapeutic effect and side effects of IPX056 compared to the immediate release version of baclofen.

In 2008, the results from an earlier study of 173 patients with spasticity due to MS reported that IPX056 reduced morning stiffness and nighttime awakenings compared to placebo as measured by the Ashworth scale. A placebo is made to look like the active medication but does not actually contain any active medication. The Ashworth scale is a 5-point rating of spasticity in which the examiner rates the amount of tone felt as a limb is moved passively through its arc of motion.

Overall the benefits of IPX056 could result in improvement in spasticity and related symptoms along with possible benefits in quality of life and patient well-being. IPX056 could reduce the number of pills a patient has to take each day. It is easier to remember to take a pill twice a day than four times a day. The slow release of the medication may also allow patients to get a more restful night of sleep without interruption due to medication wearing off and break through spasticity. The slow release of the medication may decrease side effects and improve tolerance to the medication for patients who are unable to tolerate the immediate release version of the drug. 


Stiffness, Spasticity and Spasms It is very common for people with MS to experience “tightness” or stiffness in their muscles.  Some people notice this stiffness more in the morning before their muscles warm up.  Stiffness may be caused by a decrease in flexibility when activity levels decrease, or it may be due to spasticity, a neurological effect.  If one becomes inactive due to extreme fatigue, a sedentary lifestyle, or pain related to limited movement, stiffness may occur. MS-related spasticity occurs when there is an injury to the central nervous system.  The injury results in abnormal messages being sent to the muscles which creates an increase in “tone” or muscle tightness.  Everyone needs some muscle tone to maintain an erect posture and conduct daily activities; spasticity occurs when people have abnormally high tone which may interfere with movement.  Generally the legs are more affected by spasticity than the arms or other muscles, and sometimes patients experience one side of their body being more affected than the other.   Spasticity is often triggered by rapid movements and can be quite painful.  Spasticity can also create difficulties with moving or walking and can contribute to foot drop, where an individual cannot flex the foot sufficiently to clear the toe while walking.   Severe untreated spasticity can lead to contractures (restriction of movement in joints), skin breakdown, and pain.  Therefore, spasticity should be treated aggressively.  Spasms are strong muscle contractions that tend to be painful although brief.

Many people with multiple sclerosis experience muscular symptoms. These include weakness, problems with coordination and loss of balance. The muscle-related symptoms most often occur in the arms and legs. At times, these symptoms may impair walking. Spasticity, which is the involuntary tightening of a muscle, can manifest as stiffness, pain or spasms.