Peripheral neuropathy associated with Arava

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Sep 13, 2000

Peripheral neuropathy with leflunomide

London, UK In a letter to Rheumatology, UK researchers have reported 2

cases of peripheral neuropathy associated with leflunomide (Arava®,

Aventis) in patients with rheumatoid arthritis (RA) [1].This adverse

event has not been reported previously with leflunomide, and both cases

have been documented on a yellow card submitted to the UK Committee on

Safety of Medicines.

" In both our patients, there was a tight temporal relationship between

the onset of symptoms and the use of the drug, which strongly suggests a

causative link, " say Dr MT Carulli (Guy's Hospital, London, UK) and Dr

UM Davies (East Surrey Hospital, Redhill, Surrey, UK). " This is

supported by the documented improvement of neuropathy after withdrawal

of leflunomide, while all other drug therapy, including the dose of

corticosteroids, was unchanged. "

Confirmed by nerve conduction studies

Both patients underwent nerve conduction studies, which confirmed

sensory motor peripheral neuropathy and, after drug withdrawal,

confirmed improvement. Both were taking leflunomide at a maintenance

dose of 10 mg daily (after a loading dose of 100 mg for 3 consecutive

days).

One patient developed symptoms within 2 weeks of starting leflunomide

sensory neuropathy with a stocking distribution up to the malleoli. The

drug was discontinued 4 weeks later at follow-up, and on review 3 months

later, " there was a clear and subjective improvement of the neuropathy,

confirmed by repeat conduction studies. " This 76-year old man had an

18-month history of seropositive RA, as yet nonerosive, as well as

chronic emphysema and pulmonary fibrosis. He was also taking

prednisolone, tramadol, disodium etidronate, indoramin, and celecoxib,

none of which is known to cause peripheral neuropathy, the authors

comment.

The second patient developed symptoms after 3 months on leflunomide,

reporting numbness in the fingertips and both feet extending to the

mid-shins, with clinical findings compatible with a glove-and-stocking

sensory neuropathy, the researchers write. Three months after

discontinuation, she reported a marked improvement in her symptoms,

confirmed on clinical examination and repeat nerve conduction studies.

This 69-year old woman had seropositive erosive RA of a 10-year

duration, which had previously treated with gold salts followed by

methotrexate. She was also taking prednisolone, lansoprazole,

simvastatin, losartan, and amiodarone but had been on these drugs " for a

long period without side effects, " the researchers comment.

" Rheumatologists should be aware that leflunomide can cause a reversible

neuropathy. This is an important side effect as it causes significant

disability in patients already disabled by their disease, " the

researchers conclude.

Zosia Chustecka

Cited source

1. Carulli MT, Davies UM. Peripheral neuropathy: an unwanted effect of

leflunomide? Rheumatology (Oxford) 2002 Aug; 41(8):952-3.

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Here are two links on peripheral neuropathy:

On peripheral neuropathy from NeurologyChannel.com:

http://www.neurologychannel.com/neuropathy/

(make sure you see the links at the bottom)

More on peripheral neuropathy from the National Institute of

Neurological Disorders and Stroke:

http://www.ninds.nih.gov/health_and_medical/disorders/peripheralneuropathy_doc.h\

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