Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open-label study.
OBJECTIVE
To study the safety and efficacy of infliximab plus leflunomide combination therapy in adult rheumatoid arthritis (RA).


METHODS
Twenty patients with active RA received leflunomide 100 mg for 3 days followed by 20 mg daily for 32 weeks. At week 2 all patients started infliximab 3 mg/kg, and received a further four infusions at weeks 4, 8, 16 and 24.


RESULTS
Adverse events led to 11 patients being withdrawn before the end of the study. The commonest adverse event was pruritus associated with an eczematous rash. Other serious reactions included infliximab infusion reactions in four patients and Stevens-Johnson syndrome in one. There was no relationship between the serum concentration of A77 1726, the active metabolite of leflunomide, and adverse events. The mean Disease Activity Score (DAS28) fell from 7.18 at week 0 to 5.18 (P<0.0001, paired t-test) at week 4 and remained between 3.85 and 4.85 up to week 32. In those patients remaining on treatment, more than 80% achieved an ACR20 response from week 8 to week 28, and up to 46% achieved an ACR70 response.


CONCLUSIONS
Infliximab plus leflunomide combination therapy appears to be highly efficacious in the treatment of adult RA. However, widespread use may be limited by adverse events, which were common and in some cases severe.
Kiely
P D W
PD
Department of Rheumatology, St George's Healthcare NHS Trust, Blackshaw Road, London SW17 0QT, UK.
Johnson
D M
DM
D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000209:etiology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000209:etiology; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007239:Infections / Q000209:etiology; D000069285:Infliximab; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects*; D000077339:Leflunomide; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D019226:Oral Ulcer / Q000139:chemically induced; D010865:Pilot Projects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000077339:Leflunomide