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Yimaitong edited and arranged, please do not reprint
without authorization.
This study is the first to evaluate the efficacy and safety of
7% and 17.
8%, respectively, and there was no significant difference in the time to renal lesions between the two groups (p=0.
676); In terms of safety, the incidence of adverse events (AEs) was similar
to that of patients in the LEF group (56.
5%) and the AZA group (58.
9%).
Therefore, the researchers believe that the efficacy and safety of LEF are not inferior to AZA in LN maintenance therapy, and LEF may become a new drug
candidate for LN maintenance therapy.
LN is a common and serious complication of
death.
Mycophenolate mofetil (MMF) and AZA are commonly used in maintenance therapy for LN, but are not available or tolerated
in all patients.
LEF is an immunosuppressant
widely used to treat
Several clinical trials have evaluated the role of LEF in the treatment of immune-associated kidney disease and suggested that LEF is not inferior to
in induction therapy.
To compare the efficacy and safety of LEF and AZA as maintenance therapy for LN patients, Fuqiong, deputy chief physician from the Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, conducted a 36-month study, which was recently published in Ann Rheum Dis.
(impact factor 27.
973).
Study design
This review is a prospective, multicenter, randomized, open-label study that included two treatment periods
.
➤ Induction period: patients with active LN are enrolled and treated with the NIH-CYC standard regimen (CYC 0.
5-1.
0g/m2 intravenous pulse therapy once a month for 6 months) combined with glucocorticoids (GCs
).
➤ Maintenance treatment period: Patients enrolled in complete response (CR) or partial response (PR) after 6-9 months of induction period are randomized (1:1) to receive LEF (20mg/d) or AZA (initial dose 50mg/d, target dose 100mg/d) while receiving GCs
.
The primary endpoint was the time to renal recurrence in patients with 36 months of maintenance therapy, and the key secondary endpoints were the number of patients achieving CR, changes in kidney-related indicators, and safety
.
The specific study design is shown in Table 1
.
Table 1 Study design
Note: SLEDAI: SLE disease activity index, CYC: cyclophosphamide, GC: glucocorticoids, eGFR: glomerular filtration rate, SCr: serum creatinine
Research results
A total of 270 patients were enrolled in the induction therapy phase and 215 patients were included in the maintenance therapy phase (n = 108 in the LEF group and n = 107 in the AZA group).
A total of 137 patients (63.
7%) completed 36 months of maintenance therapy (n = 72 in LEF group and n = 65 in AZA group).
Most patients receive maintenance therapy at LEF 20 mg/day or AZA 100 mg/day
.
The baseline average dose of GCs (
.
Primary endpoint
During the 36-month treatment period, the LEF group (incidence 15.
7%; median time 16 months) versus AZA group (incidence 17.
8%; median time to 14 months) was not significantly different in the time to kidney disease (p=0.
676) (Figure 1).
Fig.
1 Time of renal lesions in patients in LEF group and AZA group
Key secondary endpoints
➤ Within 36 months, the proportion of patients achieving CR was similar between the two treatment groups: 61 (56.
4%) in the LEF group and 58 (54.
2%)
in the AZA group.
➤24h urine protein, serum
was observed.
➤The number of patients with extrarenal lesions in both treatment groups was small: 1 case in the LEF group (
), and 2 cases in the AZA group (
).
Safety and tolerability
The incidence of AEs was similar
to that of patients in the LEF group (61/108 cases, 56.
5%) and the AZA group (63/107 cases, 58.
9%).
The most common AEs were hematologic abnormalities and liver function abnormalities, with no death, serious infection, or malignancy
.
In addition, at long-term follow-up, 19 patients continued to use the study drug for up to 6 years
.
No patients developed renal failure during the study period, and only one patient was discontinued due to treatment intolerance, suggesting that LEF and AZA were safe
for long-term use.
Conclusions and discussions
This study demonstrates for the first time that the efficacy and safety of LEF are not inferior to AZA
in the maintenance therapy of LN.
The results showed that at 36 months follow-up, the incidence of renal lesions in the LEF group and AZA group was 15.
7% and 17.
8%, respectively, and there was no significant difference in the time of renal lesions between the two groups (p=0.
676).
In terms of safety, the incidence of AEs in patients in the LEF group (56.
5%) was similar
to that of patients in the AZA group (58.
9%).
Long-term follow-up of 6 years found that LEF was effective in controlling renal and extrarenal lesions and was safe
and well tolerated.
The results support LEF as a drug
candidate for LN maintenance therapy.
The inclusion of LEF in LN treatment strategies is clinically important
.
First, there are currently only 2 randomized controlled trials investigating maintenance therapy for LN, and this study provides a relatively high level of evidence to support the efficacy
of LEF in maintenance therapy for LN comparable to AZA standard treatment.
In addition, although MMF is gradually being used clinically as first-line treatment for LN, MMF is not suitable for all patients
.
For example, the risk of MMF infection is significantly increased in Asians, and most patients cannot tolerate the recommended dose of MMF induction therapy (up to 3 g/day).
Secondly, the mechanism of LEF in the treatment of LN is a novel mechanism of action, which may improve the effectiveness of LN therapy and may become a drug candidate for adjuvant therapy or combination/multi-target therapy, which remains to be studied
.
Finally, patients will benefit
from the easy accessibility, long-term safety and low cost-effectiveness of LEF.
There are still limitations of this study, such as the short trial time and single population, and long-term, double-blind, placebo-controlled follow-up studies
in a more diverse and larger patient population are needed to further validate the long-term efficacy of LEF in LN maintenance therapy.
References: Fu Q, Wu C, Dai M, et al.
Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up[J].
Ann Rheum Dis.
2022 Jul 4:annrheumdis-2022-222486.
doi: 10.
1136/ard-2022-222486.
Epub ahead of print.
PMID: 35788493.
