Clinical analysis of chinese patients with rheumatoid arthritis treated with leflunomide and methotrexate combined with different dosages of glucocorticoid

Abstract

Objective: To analyze the safety of combined leflunomide (LEF), methotrexate (MTX), and glucocorticoid (GC) therapy, we investigated the adverse effects of such combination therapy in patients with early active rheumatoid arthritis (RA).

Methods: Two hundred sixty-six patients with RA who were receiving LEF and MTX therapy were randomly assigned to 3 groups, as follows: group 1 received no GC, group 2 received 7.5 mg prednisone, and group 3 received 15 mg prednisone. Adverse effects were analyzed using the χ(2) test at week 4 or the Fisher exact test at week 12.

Results: Patients in group 1 had a higher incidence of skin rash, oral ulcers, leukopenia, and liver damage than did those in groups 2 and 3 (all, P ≤ 0.05). However, the rates of osteoporosis, diabetes, hyperlipidemia, and hypertension in group 3 were statistically higher than in groups 1 and 2 (P ≤ 0.05).

Conclusion: In the treatment of RA, the incidence of skin rash, liver dysfunction, and oral ulcers may be decreased with combination therapy using LEF, MTX, and 7.5 mg prednisone, and blood pressure, blood glucose concentration, and bone density are not increased. Most important, 7.5 mg prednisone was synergistic with LEF and MTX, and such combination therapy could be a useful option as initial treatment of early active RA.

Keywords: adverse reactions; glucocorticoid; leflunomide; methotrexate; rheumatoid arthritis.

Figure 1

Patient disposition. Patients were grouped according to the treatment received (see “Materials and Methods”). LEF = leflunomide; MTX = methotrexate.

Figure 2

Comparisons of the incidence of rash, increase in alanine aminotransferase (ALT) concentration, diabetes, and hyperlipidemia in the 3 groups at weeks 4 to 12. Almost all adverse reactions at week 12 were higher than at week 4, in particular, rash and increase in ALT in group 1, and diabetes and hyperlipidemia in group 3. In addition, at week 4, the incidence of the 4 adverse effects in group 2 was relatively lower than in groups 1 and 3. Group 1, no glucocorticoid therapy (GC); group 2, 7.5 mg GC; and group 3, 15 mg GC. *P < 0.05 (significant difference).