PARIS — Combining agents with complementary mechanisms and pharmacokinetic profiles may hold promise even for patients with severe psoriatic arthritis who have been failed by every other form of therapy.
German researchers used that approach, combining leflunomide (Arava) and etanercept (Enbrel) in two severely affected patients, with excellent results.
Jochen Schmitt, M.D., and Gottfried Wozel, M.D., of the department of dermatology at University Hospital Carl Gustav Carus of Dresden University of Technology presented their findings at the European Congress on Psoriasis 2004.
Confronted with patients who had severe swollen and tender joints, extensive psoriatic plaques, and profoundly affected quality of life and for whom an array of therapeutic options had failed, they decided to combine leflunomide and etanercept.
“The rationale of the combination is based on the predominant role of T cells and proinflammatory cytokines such as TNF-α in the pathogenesis of psoriasis,” they noted in a poster presentation.
“The active metabolite of leflunomide interferes with T-cell proliferation by inhibition of dihydroorotate dehydrogenase, a key enzyme of pyrimidine de novo synthesis,” and etanercept, a TNF-αreceptor, P75 fusion protein, blocks biologic activity to TNF-αaccording to the investigators.
Leflunomide was prescribed at an initial dosage of 100 mg for 3 days, then tapered to 20 mg and then to 10 mg. Patients received etanercept in 25-mg, twice-weekly subcutaneous injections.
The response was dramatic during the course of the 8-week study period and a follow-up period that extended 20 more weeks. The first patient went from 32 swollen and 30 tender joints, a Psoriasis Area and Severity Index (PASI) score of 52.6; and a Dermatology Life Quality Assessment score (DLQI) of 19, to 9 swollen and 8 tender joints, a PASI score of 1.8, and a DLQI score of 3.
The second patient was less severely affected at baseline but exhibited a complete remission. Specifically, she went from nine swollen and nine tender joints to zero; her PASI score dropped from 17.6 to 0, and her DLQI score declined from 3 to 0.
The researchers commented on the two drugs' complementary pharmacokinetic profiles.
“Leflunomide's active metabolite exhibits an extremely long half-life in vivo. Etanercept features an early onset of efficacy. Thus, in severe psoriasis, it might be reasonable to use leflunomide as a basic agent and to add etanercept when a relapse occurs,” Dr. Schmitt said.