Reuters Health Information (2007-12-24): Incidence of infections associated with leflunomide for RA "acceptable"
Incidence of infections associated with leflunomide for RA "acceptable"
Last Updated: 2007-12-24 8:40:17 -0400 (Reuters Health)
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. Peter 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.
J Rheumatol 2007;34:2201-2203.