Lemtrada and Infusion Associated Reactions

Some of these are serious, all are unpleasant - know your risks

 Lemtrada (alemtuzumab) is one of the newer disease-modifying therapies for multiple sclerosis. It appears to be extremely effective, but comes with a number of potential side effects, some of them serious. For an overview of Lemtrada, see Is Lemtrada for MS Right for You?

Below is one of the black box warnings on Lemtrada, this one specifically about infusion associated reactions (IARs), which was taken directly from the package insert:

“LEMTRADA causes serious and life threatening infusion reactions. LEMTRADA must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for two hours after each infusion. Make patients aware that serious infusion reactions can also occur after the 2-hour monitoring period.”

How often does this happen?

According to the manufacturer, Genzyme: "In clinical trials, infusion associated reactions (IARs) were defined as any adverse event occurring during or within 24 hours of Lemtrada infusion. 82% of patients treated with Lemtrada in controlled clinical trials in MS experienced mild to moderate IARs during and/or up to 24 hours after Lemtrada 12 mg administration despite precautionary treatment with corticosteroids, and 9% of patients experienced severe IARs."

What are “serious and life threatening infusion reactions?"

Serious reactions occurred in 3% (26/919) of patients in the clinical trials.  These reactions included serious cases of:

  • Cardiac arrhythmias, such as: tachycardia (fast resting heart rate of over 100 beats per minute), bradycardia (slow resting heart rate of under 60 beats per minute) and atrial fibrillation (irregular and often rapid heart rate that commonly results in  poor blood flow to the body)
  • Pyrexia (raised body temperature, fever)
  • Urticaria (hives)
  • Nausea
  • Chest discomfort
  • Hypotension (low blood pressure)

In the follow-up study, anaphylaxis has been reported rarely.

Less serious infusion associated reactions (and their frequencies of occurrence in clinical trials) include:

  • Headache - 43.7%
  • Rash - 43.1%
  • Pyrexia - 25.2%
  • Nausea - 15.9%
  • Urticaria - 14.7%
  • Pruritus (itching) - 12.7%
  • Insomnia - 11.1%
  • Chills - 9.5%
  • Flushing - 9.5%
  • Fatigue - 8.4%
  • Dyspnea (breathing difficulties) - 7.2%
  • Dysgeusia (distortion of sense of taste) - 7.0%
  • Chest discomfort - 6.6%
  • Generalized rash - 6.5%
  • Tachycardia - 6.4%
  • Dyspepsia (indigestion) - 6.2%
  • Dizziness - 5.7%
  • Pain - 5.2%

What can be done to prevent this?

Before each infusion, people are usually given the following:

  • A 1000 mg infusion of Solu-Medrol (before the first three infusions of the first course and before all three infusions of the second course)
  • Antihistamines, such as Zyrtec or Benedryl
  • Fever-reducing drugs, usually ibuprofen (Motrin, Advil) or acetaminophen (Tylenol)

    What kind of monitoring is done for infusion associated reactions?

    An electrocardiogram (EKG) should be done and assessed before each treatment course.

    In addition, active observation for infusion-associated reactions in the clinic is recommended during and for at least 2 hours after each Lemtrada infusion, or longer at the discretion of the physician. Patients should be educated to look for signs and symptoms of infusion associated reactions particularly for the first 24 hours after each Lemtrada infusion.

    What if an infusion associated reaction occurs?

    If an IAR occurs, provide the appropriate symptomatic treatment, as needed. If the infusion is not well tolerated, the infusion duration may be extended. If severe infusion reactions occur, immediate discontinuation of the IV infusion should be considered. Physicians should be familiar with the patient’s cardiac history, since infusion-associated reactions can include cardiac symptoms such as tachycardia.

    Resources for the treatment of anaphylaxis should be immediately available.

    Bottom Line: This list of infusion associated reactions is daunting. If I was considering Lemtrada, I would pretty much come to terms with the fact that I would likely feel pretty terrible during the course of treatment. It should be noted, that only 3% of the IARs were considered "serious" (I'm not sure how many were considered "life threatening," however). To take Lemtrada or not is clearly not a decision to be taken lightly, but if it looks like it is an appropriate medication for your situation, it is important to understand the side effects and what can be done to lessen or prevent them.

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