Efficacy and safety of weekly leflunomide for the treatment of early rheumatoid arthritis: a randomized, multi‐center study

Abstract

Aim: The aim of this study was to determine the efficacy and safety of a weekly dose of leflunomide (50 mg/ week) in early rheumatoid arthritis patients with mild or moderate disease activity. Methods:The patients of early rheumatoid arthritis (ERA) with mild or moderate disease activity were randomly selected for inclusion in this study and were assigned to either the treatment group (leflunomide 50 mg/week, LEF50) or the control group (leflunomide 10 mg/day, LEF10). All patients were treated for 24 weeks. Clinical efficacy was assessed using the disease activity score in 28 joints (DAS28) -erythrocyte sedimentation rate (ESR) and European League Against Rheumatism (EULAR) response. A Chi-squared test, Fisher's exact-test and paired t-tests were used to analyze the data.Results: A total of 244 patients who met the inclusion criteria and received at least one medicine dose were analyzed. At the baseline, the DAS28 (ESR) of the ERA patients were 4.41 AE 0.69 in LEF 50 group and 4.52 AE 0.64 in LEF 10 group, respectively. At week 24, the DAS28 (ESR) in two groups ( 2.94 AE 1.10 and 3.02 AE 1.14 ) were significant decreased compare with the baseline, respectively (P<0.01). There was no significant difference in DAS28 (ESR) between the LEF50 and LEF10 groups at week 24. (P > 0.05). At weeks 8, 12 and 24, the EULAR response (good responses + moderate responses) were 47.6%, 58.7% and 59.5%, in the LEF50 group and 43.2%, 49.1% and 53.4% in the LEF10 group, respectively. There was no significant different of EULAR response rates in the two groups at week 8, 12, and 24, respectively (P>0.05). There was no serious adverse events during the study. Conclusion:A weekly dose of 50 mg leflunomide showed similar benefits to a daily dose of 10 mg leflunomide for the treatment of mild-to-moderate early rheumatoid arthritis.

Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis

“…One study compared a loading dose of leflunomide (100 mg×1 for 3 days) with a fixed dose of 20 mg daily and did not show differences in efficacy but a better safety profile for the fixed dose 16. A weekly dose of 50 mg leflunomide showed similar benefits to a daily dose of 10 mg leflunomide for the treatment of mild-to-moderate early RA 17. The latter however was an open superiority study with a high RoB and 10 mg leflunomide daily is considered a suboptimal dose.…”

Leflunomid w leczeniu chorób reumatycznych — znaczenie różnorodności stosowanych dawek

“…Roz-waża się również zmniejszenie stosowanej docelowej dawki leku do 10 mg/dobę, zwłaszcza w przypadku politerapii [26]. W ostatnich latach dyskutuje się nawet nad zmniejszeniem dawki leflunomidu do 50-100 mg/tydzień [27,28], choć nie wszystkie badania potwierdzają równoważność tak małych dawek leflunomidu [29]. Wydaje się, że maksymalne prawdopodobieństwo sukcesu klinicznego oraz jednocześnie największego bezpieczeństwa terapii można uzyskać, wybierając dawkę, która utrzymuje docelowe stężenie leku w surowicy powyżej 13 mg/l.…”

Weekly versus daily leflunomide

“…The results of this study showed that weekly administration is easy, low cost, and has good safety. This treatment protocol also increased patient compliance despite maintaining the therapeutic properties of leflunomide (6).…”