Incidence of Infections Associated With Leflunomide (Arava)

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Incidence of Infections Associated With Leflunomide for RA " Acceptable "

J Rheumatol 2007;34:2201-2203.

http://www.medscape.com/viewarticle/567910?src=mp

NEW YORK (Reuters Health) - Among patients with rheumatoid arthritis (RA) in

New Zealand, the rate of serious infection associated with leflunomide

treatment is " acceptable in the context of optimally treating active RA, "

report Dr. T. Chapman of Christchurch Hospital and colleagues in the

November issue of the Journal of Rheumatology.

They note that the government did not fund a TNF-blocker in New Zealand

until 2006, and treatment of RA has relied on disease modifying

antirheumatic drugs. Leflunomide was rarely used until 2002, when it

received funding.

The team conducted an audit of all 171 RA patients who initiated leflunomide

therapy at Christchurch Hospital between 2002 and 2006. The patients took an

average of 16.8 mg of leflunomide daily for an average of 23.4 months.

According to the investigators, 11 patients developed severe infections

requiring hospitalization while taking leflunomide, yielding an incidence of

severe infection of 3.30 per 100 patient-years. This is similar to a recent

audit from the UK comparing DMARD-treated and anti-TNF-treated patients, Dr.

Chapman and colleagues note.

Among the 11 patients with severe infections, three developed lower

respiratory tract infections, two developed cellulitis, two had disseminated

herpes zoster, and one each developed probable hepatic TB, abdominal sepsis,

mycotic aneurysm, and gastroenteritis.

Patients with severe RA and those taking concomitant methotrexate and

corticosteroids were at greatest risk for severe infection, the researchers

found. Nine of the 11 patients who developed severe infections were taking

corticosteroids or corticosteroids with methotrexate simultaneously with

leflunomide.

In addition to these 11 cases, the New Zealand Pharmacovigilance Centre has

been notified of 7 additional reports of severe infections in RA patients

taking leflunomide, the authors note in their report, including probable

pulmonary TB (1), pneumocystis pneumonia (1), other pulmonary infection (2),

and septicemia (3) including a case of infective endocarditis.

Four of these infections occurred in patients taking leflunomide in

combination with methotrexate and one in combination with adalimumab. All

five of these patients were also taking corticosteroids.

While they believe the risk of serious infection is acceptable, Dr. Chapman

and colleagues also report that " in our experience, once established,

infections may rapidly progress in patients with RA taking leflunomide. "

Therefore, " early cholestyramine washout is strongly recommended, " they

write.