Leflunomide-associated infections in rheumatoid arthritis.
OBJECTIVE
To determine the prevalence of severe infections in patients with rheumatoid arthritis (RA) prescribed leflunomide in North Canterbury, New Zealand.


METHODS
A case-note audit of all Christchurch Hospital patients with RA prescribed leflunomide between 2002 and 2006 was performed. The criterion for severe infection was inpatient hospitalization. Relevant reports to the national Pharmacovigilance Centre were also examined.


RESULTS
Since January 2002, 171 patients with RA have commenced taking leflunomide. Ninety-nine of 171 (57.9%) patients were also prescribed prednisone. Combination disease modifying antirheumatic drug therapy was common, with 82/171 (48.0%) taking methotrexate (MTX), 15/171 (8.8%) hydroxy-chloroquine, 11/171 (6.4%) sulfasalazine, and 8/171 (4.7%) anti-tumor necrosis factor therapy. Eleven patients developed infection requiring hospitalization while taking leflunomide including: lower respiratory tract infections (3), cellulitis (2), disseminated herpes zoster (2), probable TB liver (1), abdominal sepsis (1), mycotic aneurysm (1) and gastroenteritis (1). Nine of the 11 patients were also taking corticosteroids or corticosteroids with MTX. The 171 patients were treated for a total of 4005 months, giving an incidence for severe infection of 3.30/100 patient-years (95% CI 1.65-5.90). Patients at increased risk were those with severe disease and taking concomitant MTX and corticosteroids. The NZ Pharmacovigilance Centre has received 7 additional reports of severe infections in patients with RA taking leflunomide. Reported cases include probable pulmonary TB (1), pneumocystis pneumonia (1), other pulmonary infection (2), and septicemia (3) including a case of infective endocarditis. Four occurred in combination with MTX, one with adalimumab. All 5 patients were also taking -corticosteroids.


CONCLUSIONS
We believe this observed rate of serious infection is acceptable in the context of optimally treating active RA. Patients with severe disease and taking combination MTX and corticosteroids are at greatest risk. In our experience, once established, infections may rapidly progress in patients with RA taking leflunomide, and early cholestyramine washout is strongly recommended.
Jenks
Katey A
KA
Department of Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch, New Zealand.
Stamp
Lisa K
LK
O'Donnell
John L
JL
Savage
Ruth L
RL
Chapman
Peter T
PT
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002481:Cellulitis / Q000209:etiology; D005260:Female; D006760:Hospitalization; D006801:Humans; D007239:Infections / Q000209:etiology*; D007555:Isoxazoles / Q000009:adverse effects*; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D018805:Sepsis / Q000209:etiology; D013203:Staphylococcal Infections / Q000209:etiology; D014386:Tuberculosis, Hepatic / Q000209:etiology
D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide