Friday, 6 April 2018

Are you about to be treated with Alemtuzumab?

If you are about to be treated with alemtuzumab you may want to know about acute acalculous cholecystitis?  

Acalculous cholecystitis with pericholecystic fluid collection as demonstrated by abdominal computed tomography scans (G). (Figure from ResearchGate)
This is a relatively new complication that occurs early after starting alemtuzumab infusions. I can hear you all saying 'Oh no, not something else to consider when making a decision to go high-efficacy high-risk'.


Acalculous cholecystitis is inflammation of the gallbladder without evidence of gallstones or bile duct obstruction. It can be a severe illness that is a complication of various medical or surgical conditions, including the administration of alemtuzumab. The condition causes approximately 5-10% of all cases of acute cholecystitis and is usually associated with more serious morbidity (sickness) and higher mortality (death) rates. It is most commonly observed in the setting of very ill patients; e.g. patients on ventilators, with sepsis or burn injuries and after severe trauma. Acalculous cholecystitis is associated with a higher incidence of gangrene and gallbladder perforation compared to calculous (gallstone/s) disease. 

I recall looking after a patient with acalculous cholecystitis when I was a house officer. She had an acute abdomen and had to have an emergency cholecystectomy. At surgery, she had a gangrenous gallbladder. She managed to pull through but she spent many weeks in ITU.

The usual presentation is of sudden onset right upper quadrant abdominal pain. Imaging studies typically reveal a distended acalculous gallbladder with thickened walls (>3-4 mm) with or without pericholecystic fluid (that is fluid around the gallbladder, see picture above). 

When you search the EMA's EudraVigilance Database (3-April-2018) there are quite a few case reports under Lemtrada that could be due to acalculous cholecystitis. 

Biliary tract disorder = 1
Cholecystitis = 8
Acute Cholecystitis = 11
Gall bladder enlargement = 3
Gallblader edema = 2

Total = 25 cases

If you are about to be treated, or retreated, with alemtuzumab please take abdominal pain seriously in the first few days and weeks after being treated. 

Croteau et al. Acute acalculous cholecystitis: A new safety risk for patients with MS treated with alemtuzumab. Neurology. 2018 Mar 30.

OBJECTIVE: To evaluate acute acalculous cholecystitis (AAC) as a potential safety risk for patients treated with alemtuzumab.


RESULTS: Eight spontaneously reported cases meeting the case definition of AAC in close temporal association with alemtuzumab use were identified. 

CONCLUSIONS: AAC represents a new and potentially life-threatening adverse event associated with alemtuzumab use in relapsing-remitting multiple sclerosis. In cases seen to date, early and conservative treatment resulted in good clinical outcomes, Awareness of this safety risk by general and speciality neurologists is important for prompt recognition and optimal management.

ProfG    

6 comments:

  1. What is the chance of any serious (potentially life-threatening) adverse events, joint disease after alemtuzumab treatment? (ITP, cancer, kidney disease etc.)

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  2. Given the rather frightening side effect profile of Alemtuzumab, to the folks at Barts and London prefer giving oral Cladribine? Don't both treatment regimens achieve the same goals? Immune system reconstitution?

    What are your clinical experiences with oral Cladribine and progressive MS? I've heard that there will be PPMS trials for Alemtuzumab. Do you think there's any chance of success for the drug in this regard? And if success is demonstrated, wouldn't this argue for success in all of the immuno ablative therapies (HSCT, Alemtuzumab, oral cladribine)?

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    1. Cladribine doesn't work as well as evidenced by clinical trial results and brain atrophy data.

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    2. The data from alemtuzumab trials involved people who had been diagnosed a few years less i the aslemtuzumab treated cohort, so whilst you may be right, it needs to be comparable

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  3. Of course it is useful to know about secondary illness following lemtrada but PML is more common following tysabri? And what is the rate of cancer following cladribine?
    A comparison of each of the big players and their serious side effects would be helpful because this blog often seems quite anti lemtrada.

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    Replies
    1. These posts follow publications when cancel and cladribine papers appear we wll post on them.

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