Literature analysis of leflunomide-induced interstitial pneumonia / 中国药房

OBJECTIVE To study the clinical characteristics of leflunomide-induced int erstitial pneumonia （Lef-IP），and to provide reference for its clinical diagnosis ，treatment and prevention. METHODS Lef-IP cases published in domestic and foreign journals from January 2004 to June 2021 were collected. Relevant information of patients were extracted and analyzed retrospectively， including basic characteristics ，clinical manifestations ，imaging manifestations ，laboratory examinations ， histopathological examinations ，treatment and outcome. RESULTS A total of 54 Lef-IP patients from case reports of 24 publications were included ，with a median age of 61 years（9-83 years）. Pulmonary symptoms appeared from 3.3 weeks to 132.9 weeks（median time of 14.5 weeks）. Patients with a loading dose of leflunomide have a shorter median time to pulmonary symptoms appearing （7.5 weeks）. The main clinical manifestations were dyspnea （85.2％），cough（57.4％），fever（53.7％）. CT imaging examination showed 19 cases with ground-glass shadow in both lungs ，and 29 cases showed interstitial infiltration in both lungs on chest radiograph；blood gas analysis showed hypoxemia and hypocapnia ；the levels of C-reactive protein and Krebs von Den lungen- 6 （KL-6）increased；histopathological examination mainly showed interstitial pneumonia （8 cases），including 3 cases of diffuse alveolar injury ，4 cases of lymphocytes in bronchoalveolar lavage fluid ，and 1 case of noncaseating granuloma. After discontinued leflunomide and symptomatic treatment （antibiotics，hormones，colecenamine，plasma exchange ），35 patients（64.8％）recovered or improved their lung symptoms. Twelve patients （22.2％）died，and patients with fever may had a higher mortality rate （34.5％， P＝0.02）. CONCLUSIONS The main clinical manifestations of Lef-IP are dyspnea ，cough and fever. Loading doses of leflunomide should be avoided at the beginning of treatment. When lef-IP occurs ，leflunomide is discontinued and corresponding treatment is given，and most of the patients ’pulmonary symptoms can return to normal or be improved.

Efficacy and safety of leflunomide in treatment of Henoch-Sch?nlein purpura nephritis with nephrotic proteinuria in children / 中国小儿急救医学

Objective:To compare the efficacy and safety of leflunomide(LEF)to mycophenolate mofetil(MMF)and cyclophosphamide(CTX)in the treatment of Henoch-Sch?nlein purpura nephritis(HSPN)in children with nephrotic proteinuria.Methods:Thirty-nine children who were diagnosed as HSPN with nephrotic proteinuria were randomly divided into three groups: LEF group, MMF group and CTX group.Each group had 13 children.Proteinuria, hematuria, adverse effect and cost were followed up at 1, 3, 6 and 9 months of medication.Results:Proteinuria and hematuria were significantly decreased in each group at 1, 3, 6 and 9 months of medication.Compared to CTX group, proteinuria and hematuria in LEF group and MMF group were lower at 9 months.It was probably associated with one child whose proteinuria did not completely return to normal at 9 months and another child who suffered from a relapse of proteinuria and hematuria at 6.5 months in CTX group.The results suggested that the efficacy of LEF and MMF was slightly better than CTX.During the observation period, all children were well tolerated and no serious adverse reactions occurred.One case showed a slight increase of alanine aminotransferase at 1 month, and returned to normal range at 3 months without any medication in MMF group.The cost of LEF group was(8 231±665)RMB and CTX group was(11 523±469)RMB which was significantly lower than(19 953±386)RMB in MMF group.Conclusion:LEF is as effective as MMF and CTX in the treatment of HSPN with nephrotic proteinuria in children.The adverse reactions of LEF are mild, and the cost is cheaper.LEF is worth popularizing in clinical practice.

Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the effects of arsenic trioxide (As@*METHODS@#Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique. Four groups of recipient rats (n=6 in each) were treated with normal saline (control), As@*RESULTS@#Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As@*CONCLUSION@#Combination treatment with As

Huangkui capsule in combination with leflunomide improves immunoglobulin a nephropathy by inhibiting the TGF-ß1/Smad3 signaling pathway.

OBJECTIVES: To investigate the efficacy and potential molecular mechanism of Huangkui capsule in combination with leflunomide (HKL) for the treatment of immunoglobulin A nephropathy (IgAN) METHODS: IgAN rat models were constructed by treating rats with bovine serum albumin, lipopolysaccharide, and tetrachloromethane. Th22 cells were isolated from the blood samples of patients with IgAN using a CD4+ T cell isolation kit. The expression levels of the components of the TGF-β1/Smad3 signaling pathway, namely, TGF-β1, Smad2, Smad3, Smad4, and Smad7, were detected using quantitative reverse transcription polymerase chain reaction. Cell proliferation was determined using the MTT assay, cell viability was determined using the WST 1 method, and the chemotaxis of Th22 cells was observed using the wound healing assay. Changes in the histology of the kidney tissues were analyzed using hematoxylin and eosin staining. RESULTS: Compared with IgAN rats, the rats subjected to HKL treatment showed good improvement in kidney injuries, and the combined drug treatment performed much better than the single-drug treatment. In addition, following HKL treatment, the viability, proliferation, and chemotaxis of Th22 cells dramatically decreased (*p<0.05, **p<0.01, and ***p<0.001). In addition, CCL20, CCL22, and CCL27 levels decreased and the expression of the key components of the TGF-β1/Smad3 signaling pathway was downregulated in IgAN rats and Th22 cells (*p<0.05, ***p<0.001). CONCLUSIONS: By targeting the TGF-β1/Smad3 signaling pathway, HKL treatment can improve kidney injury in IgAN rats as well as the excessive proliferation and metastasis of Th22 cells.

Emerging intervention of antidepressant with DMARD in non-cancerous nociceptive persistent pain associated depression in FCA induced rheumatoid arthritic rats

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, systemic complications and premature mortality. Depression has also been identified as a problem for persons with RA. This association remaining significant even after the degree of disease activity is controlled. In the present study, the efficacy of combination therapeutic effect of antidepressant (amitriptyline) with Disease Modifying Anti rheumatoid drug (leflunomide) was determined in rheumatoid arthritis pain associated depression in Freund's complete adjuvant (FCA) induced arthritic rats. Drug treatment was started 9 days after induction of FCA induced arthritis in rats. The antiarthritic activity was assessed by measuring paw volume, weight-bearing, hematological, biochemical, serological parameters, Radiographic analysis and Histopathology of tibiotarsal joints. The antidepressant activity was assessed by Forced swimming test, Rota-rod test and confirmed by estimation of brain neuro transmitters (serotonin and norepinephrine) level. Results of this study revealed that leflunomide and amitriptyline combination showed more significant (p<0.001) antiarthritic and antidepressant action and leflunomide alone treatment showed significant (p<0.001) antiarthritic activity only as compared to arthritic control. The leflunomide and low dose amitriptyline combination found to be more effective in pain associated depression in rheumatoid arthritic rats

Mechanism of leflunomide in regulating pulmonary fibrosis by regulating miR-449a / 药学实践杂志

Objective To investigate the mechanism of leflunomide (LEF) in regulating pulmonary fibrosis by regulating microRNA (miR)-449a. Methods Human lung fibroblasts MRC-5 were divided into 6 groups: control group, LEF group, LEF+mimic group, mimic group, LEF+inhibitor group and inhibitor group. MiR-449a was overexpressed or silenced by plasmid transfection with miR-449a mimic or inhibitor and ncubate for 48 h at 5 mg / L LEF. The cell viability, cell proliferation ability and apoptotic rate of each group were measured by CCK-8 method, clone formation experiment and flow cytometry. Immunofluorescent staining was used to detect α smooth muscle actin (α-SMA) and collagen I (col I). The levels of miRNA and protein were detected using qPCR and Western blot, respectively. Results The miR-449a level in the mimic group was significantly higher than that in the control group (P<0.05). The level of miR-449a in LEF group and inhibitor group was significantly lower than that in control group (P<0.05). The expression level of miR-449a in LEF+mimic group was significantly higher than that in LEF group, and the level of miR-449a in LEF+inhibitor group was significantly lower than that in LEF group (P<0.05). The cell viability and cell proliferation ability of the LEF group and inhibitor group were significantly higher than those of the control group (P<0.05). The cell viability and cell proliferation ability of the mimic group were significantly lower than those of the control group (P<0.05). The cell viability and cell proliferation ability of the LEF+mimic group were significantly lower than those of the LEF group, while the cell viability of the LEF+inhibitor group was significantly higher than that of the LEF group (P<0.05). The apoptosis rate of LEF group and inhibitor group was lower than that of control group (P<0.05). The apoptosis rate of mimic group was significantly higher than that of control group (P<0.05). The apoptosis rate of LEF+mimic group was significantly higher than that of LEF group, while the apoptosis rate of LEF+inhibitor group was significantly lower than that of LEF group (P<0.05). The fluorescence intensity of α-SMA and Col I proteins in LEF group and inhibitor group were significantly higher than those in control group (P<0.05). The relative fluorescence intensity of mimic group was lower than that of control group (P<0.05). The relative fluorescence intensities of α-SMA and Col I proteins in LEF+mimic group were significantly lower than those in LEF group, while the relative fluorescence intensities of α-SMA and Col I protein in LEF+inhibitor group were significantly higher than those in LEF group (P<0.05). The levels of p-JNK / JNK in LEF group and inhibitor group were higher than those in control group (P<0.05). The p-JNK / JNK level in the mimic group was significantly lower than that in the control group (P<0.05). The level of p-JNK / JNK in LEF+mimic group was significantly lower than that in LEF group, while the level of p-JNK / JNK in LEF+inhibitor group was significantly higher than that in LEF group (P<0.05). Conclusion LEF may activate the JNK pathway by inhibiting the expression of miR-449a in lung fibroblasts, thereby inducing fibroblast activation and proliferation, inhibiting apoptosis, and causing pulmonary fibrosis.

Combination of Methotrexate and Leflunomide for Adult-onset Still's Disease: A Case Report and Literature Review

The treatment of adult-onset Still's disease (AOSD) aims to control systemic inflammation and prevent organ damage. Systemic inflammation can be controlled with corticosteroid (CS) monotherapy in most cases. However, symptoms often flare as CS is tapered, often requiring long-term CS treatment, with its associated risks of infection, cardiovascular disease, and osteoporosis. Disease-modifying antirheumatic drugs (DMARDs) are often used as CS-sparing agents; however, the choice of DMARD has been largely empirical. Methotrexate (MTX) is recommended as the first-line steroid-sparing drug due to its well-known efficacy and safety in rheumatoid arthritis (RA). When MTX treatment is unsuccessful in AOSD, the choice of a second-line drug has not been established. In RA, leflunomide (LEF) has been used as an alternative to or in combination with MTX. To date, there has been no adequate assessment of the combination of LEF and MTX in AOSD. Here, we report a case of refractory chronic AOSD successfully treated with the MTX-LEF combination.

Curative effect of leflunomide combined with total glucosides of paeony on rheumatoid arthritis / 中国基层医药

Objective To observe the clinical effect of leflunomide combined with total glucosides of paeony (TGP) on rheumatoid arthritis (RA).Methods From September 2014 to June 2016,83 RA patients in Jiuquan People's Hospital were selected in the research,and according to time sequence seeing doctors,the patients were divided into control group (41 patients) and treatment group (42 patients).The patients of the two groups were orally given leflunomide (20 mg,1 time/d),while the treatment group was added with TGP (0.6 g,3 times/d).The patients of the two groups were treated for one month.The changes of clinical indicators such as RF,ESR,CRP,2-dimer of the two groups before and after treatment were observed.Results Before treatment,the RF,ESR,CRP,2-dimer between the two groups had no statistically significant differences (all P ＞ 0.05).After treatment,the RF,ESR,CRP,2-dimer of treatment group were (76.9 ±25.6)U/L,(18.5 ±6.3)mm/h,(15.4 ±6.3) rmg/L,(5.22 ±4.65) mg/L,respectively,which of the control group were (99.6 ±32.7)U/L,(27.8±8.6) mm/h,(21.7 ±7.8) mg/L,(14.08 ±5.76)mg/L,respectively,the differences between the two groups were statistically significant (t =3.480,5.230,4.680,4.513,all P ＜ 0.05).The total effective rate of the treatment group was 83.33 ％,which was higher than 58.54％ of the control group,the difference was statistically significant (x2 =5.330,P ＜ 0.05).Conclusion The clinical effect of leflunomide combined with TGP in the treatment of RA is better than leflunomide.

Therapeutic effect of Tengmei decoction combined with leflunomide and methotrexate in the treatment of patients with rheumatoid arthritis / 中国基层医药

Objective@#To investigate the clinical efficacy of Tengmei decoction combined with leflunomide and methotrexate in the treatment of patients with rheumatoid arthritis.@*Methods@#From February 2015 to February 2017, 72 patients with heat-tolerant rheumatoid arthritis were enrolled in Linhai Hospital of Traditional Chinese Medicine (TCM). They were randomly divided into treatment group and control groupaccording to the digitaltable, with 36 cases in each group.The control group was given leflunomide (20mg/time, 1 time/d) combined with methotrexate (15mg/time, 1 time/week). The treatment group was given Tengmei decoction on the basis of the control group.Both two groups were treated for 12 weeks.TCM symptom scores, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), platelet (PLT), joint disease activity (DAS) score, tender joint count (TJC) and swollen joint count(SJC)before and after treatment were compared between the two groups.The clinical efficacy and adverse reactions after treatment were observed.@*Results@#The total effective rate of the treatment group was 88.89%, which was significantly higher than that of the control group (69.44%), the difference was statistically significant (χ2=4.126, P=0.042). After treatment, the TCM symptom scores (morning stiffness, joint swelling and joint pain etc.), DAS score, TJC and SJC levels in the two groups, were significantly decreased(ttreatment group=28.935, 26.430, 25.824, 6.889, 9.222, 5.437; tcontrol group=23.790, 21.704, 21.685, 3.312, 8.134, 2.379, all P<0.05), and those in the treatment group decreased more significantly (t=10.004, 5.488, 7.593, 3.511, 2.554, 3.764, all P<0.05). After treatment, the ESR, RF, CRP, PLT levels of the treatment group and ESR, RF, CRP levels of the control group were significantly decreased (ttreatment group=3.969, 2.821, 5.970, 2.791, tcontrol group=5.240, 2.246, 5.452, all P<0.05), and the ESR and CRP levels in the treatment group were significantly lower than those in the control group (t=2.394, 3.895, all P<0.05).@*Conclusion@#The efficacy of Tengmei decoction combined with leflunomide and methotrexate in the treatment of patients with heat-toxic phlegm-restricted rheumatoid arthritis is effective, which can effectively reduce inflammatory indicators and improve TCM symptom scores, and is safe and reliable.

Effects of leflunomide on serum vascular endothelial growth factor and endothelin in patients with IgA nephropathy / 重庆医学

Objective To observe the efficacy and safety of prednisone combined with leflunomide in the treatment of immu-noglobulin A(IgA)nephropathy.Methods Eighty patients with IgA nephropathy were selected and divided into the treatment group and control group.The patients in the control group were given prednisone and the treatment group received prednisone plus leflunomide.The treatment course lasted for 12 months.Total effective rate,serum creatinine(Scr),urinary protease inhibitor C(Cys C),blood urea nitrogen(BUN)and 24 h proteinuria(U-prot)were measured at 6-month and 12-month treatment.Serum levels of vascular endothelial growth factor(VEGF)and endothelin-1(ET-1)were measured by enzyme-linked immunosorbent assay (ELISA).Results The effective rates at 6-month and 12-month treatment in the treatment group were 85% and 90% respective-ly,which in the control group were 65% and 70% respectively,the difference between the two groups was statistically significant (P<0.05).The BUN and U-prot levels after 6-moth and 12-month treatment were significantly reduced,moreover the effect in the treatment group was better than that in the control group(P<0.05).The levels of plasma VEGF and ET-1 after 6-moth and 12-month treatment in the two groups were decreased,moreover the decrease range in the treatment group was greater than that in the control group(P<0.05).Conclusion Prednisone combined with leflunomide can significantly improve the renal function in the pa-tients with IgA nephropathy,and it is safe and effective.

Clinical efficacy of methotrexate combined with leflunomide in the treatment of rheumatoid arthritis / 中国基层医药

Objective To investigate the clinical efficacy of methotrexate combined with leflunomide in the treatment of rheumatoid arthritis. Methods From January 2017 to February 2018,90 patients with rheumatoid arthritis in Shengzhou Hospital of Traditional Chinese Medicine were divided into control group and observation group according to the random number table method,with 45 cases in each group. The control group was treated with metho-trexate,the observation group was treated with methotrexate and leflunomide. The clinical efficacy of the two groups was evaluated. The anti - cyclic citrullinated peptide antibody (ACCP),rheumatoid factor (RF),and C - reactive protein (CRP) levels were measured before and after 4 months of treatment. The adverse reactions were recorded. Results The total effective rate in the observation group was 95. 56％ after 4 months of treatment,which was signifi-cantly higher than 80. 00％ in the control group (χ2 = 8. 196,P = 0. 016). The ACCP,RF and CRP levels in the two groups were significantly decreased after treatment for 4 months. The ACCP,RF and CRP levels in the observation group were (12423. 68 ± 174. 82) U/ L,(6. 24 ± 2. 14) U/ L,and (6. 69 ± 3. 32) mg/ L,respectively,which were significantly lower than those in the control group [(15421. 27 ± 287. 33) U/ L,(16. 58 ± 3. 26) U/ L,(10. 14 ± 5. 22)mg/ L,t = 59. 787,17. 786,3. 741,P = 0. 000,0. 000,0. 000]. The incidence rate of adverse reaction in the observation group was 6. 67％ ,which in the control group was 4. 44％ ,the difference between the two groups was not statistically significant ( χ2 = 0. 211, P = 0. 645). Conclusion Methotrexate combined with leflunomide in the treatment of rheumatoid arthritis can significantly improve the clinical efficacy,reduce the serum ACCP,RF,CRP levels in patients with a certain degree of control of the disease,while not increasing adverse reactions,has certain degree of safety.

Effect of leflunomide combined with methotrexate in the treatment of skin lesions caused by psoriatic arthritis / 中国基层医药

Objective To study the clinical effect of leflunomide combined with methotrexate in the treatment of skin lesions caused by psoriatic arthritis .Methods The clinical data of 90 patients with skin lesions caused by psoriatic arthritis were collected ,and they were divided into control group and observation group by simple random method,45 cases in each group.The control group was treated with methotrexate ,and the observation group was given leflunomide combined with methotrexate .Before treatment and after treatment for one month ,two months ,three months ,the skin lesions , psoriatic arthritis symptoms improvement , clinical effects and adverse reactions were observed in the two groups.Results After treatment for one month,two months,three months,the DLQL index scores in the observation group were (8.12 ±2.02)points,(6.55 ±1.47)points,(3.68 ±1.21)points,respectively,which were significantly better than those in the control group (t=2.54,3.92,4.44,P=0.01,0.01,0.01).After treatment for one month,two months,three months,the PASI index scores in the observation group were (7.57 ±3.22)points, (4.61 ±1.86)points,(3.11 ±2.17)points,respectively,which were better than those in the control group (t=3.42, 7.81,4.07,P =0.01,0.01,0.01).The total effective rate of the observation group was 88.89％,which was significantly higher than 68.89％of the control group (χ2 =5.40,P=0.02).No serious adverse reactions occurred in both two groups,and the difference was not statistically significant (11.11％ vs.13.33％,χ2 =0.10,P=0.75). Conclusion Compared with methotrexate alone , leflunomide combined with methotrexate in the treatment of skin lesions caused by psoriatic arthritis has obvious effect , and can significantly improve the symptoms of patients with skin and arthritis symptoms ,and it is more conducive to relieve patients'pain.

Investigation of the DHODH Genetic Polymorphism (19C ＞ A) Response to Leflunomide Treatment in Rheumatoid Arthritis / 医学研究杂志

Objective Purpose leflunomide (LEF) is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA).It is a prodrug that is rapidly converted in vivo to the active metabolite A77 1726.The mechanism of action of A77 1726 primarily involves inhibition of the enzyme DHODH.Related studies have found that DHOD gene has polymorphism.The aim of this study was to investigate whether genetic polymorphisms in DHODH (19C ＞ A) influence leflunomide pharmacokinetics and treatment response.Methods We studied 105 patients diagnosed with RA and treated with LEF (20 mg daily).Follow-up was 6 months.Clinical improvement was valuated according to the American College of Rheumatology 20％ and 50％ response criteria.The peripheral blood genomic DNA was extracted,and amplified by PCR,analyzed by direct sequencing.The gene detection was performed in our hospital 105 patients with DHODH polymorphism(19C ＞ A).Results After 3 months of therapy,the ACR20 criteria was met by 70.0％ in C allele,51.7％ in A allele.Differences were statistically significant(P =0.012).The ACR50 criteria was met by 38.0％ in C allele,28.3％ in A allele.It did not reach statistically significant(P =0.185).After 6 months of therapy,the ACR20 criteria was met by 84.7％ in C allele,61.7％ in A allele.Differences were statistically significant (P =0.006).The ACR50 criteria was met by 60.7％ in C allele,38.3 ％ in A allele.Differences were statistically significant(P =0.039).Conclusion The remission rate of ACR20 and ACR50 in patients with rheumatoid arthritis was increased with the treatment time.The results of the study suggest that DHODH(19C ＞ A) polymorphism may be associated with LEF treatment outcome in RA patients.Treatment response is better in the patients with the C allele than A allele.This trend is more obvious with the extension of time.

Efficacy of low-dose leflunomide in lupus nephritis: A multi-center prospective study / 中华肾脏病杂志

Objective To investigate the efficacy of leflunomide combined with prednisone in the induction therapy of proliferative lupus nephritis (LN).Methods A prospective,multicenter,randomized controlled clinical trial was conducted in patients with biopsy-proved proliferative lupus nephritis recruited from 15 renal centers from 2013 to 2015.Patients were randomized to two groups.Oral leflunomide or intravenous cyclophosphamide was given to patients in each group.Both groups received a tapering course of oral prednisone therapy.All patients were followed up for 24 weeks.The blood biochemistry,urine index,clinical curative effect and adverse reaction were recorded and analyzed statistically.Results A total of 100 patients were enrolled in this clinical trial,including 48 patients in leflunomide group and 52 patients in cyclophosphamide group.After 24 weeks,the overall response rate was 79％ (95％ CI 67％-90％) in the leflunomide group and 69％ (95％ CI 56％-82％) in the cyclophosphamide group.23％ (95％CI 11％-35％) of patients in leflunomide group showed complete remission compared with 27％ (95％CI 24％-30％) in cyclophosphamide group (P=0.35).The levels of 24-hr urine protein excretion,SLEDAI and anti-dsDNA antibody titers were decreased in patients treated with leflunomide group after 24-weeks treatment.And the levels of serum albumin and complement 3 after treatment were significantly higher compared with these before treatment.There was also no significant difference in changes of 24-hr urine protein excretion,SLEDAI score,anti-dsDNA antibody titers,serum albumin and complement C3 levels after treatment between two groups.Incidence of adverse events did not differ between the leflunomide and cyclophosphamide group.Conclusions Leflunomide combined with prednisone showed same efficacy compared with cyclophosphamide as induction therapy for lupus nephritis.Leflunomide might be an useful medicine in the induction therapy of lupus nephritis.

Predictors of response in patients with progressive IgA nephropathy treated with leflunomide and medium/low-dose corticosteroid / 中华肾脏病杂志

Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria＞ 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62％,64％,67％ and 74％,respectively.Seventeen (40.5％) and fourteen (33.3％) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P ＜ 0.01).The decrease rate was 31.3％.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4％) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95％ CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.

Preliminary Prediction of Bioequivalence of Leflunomide Tablets Based on Analysis of Solublility and Permeability / 中国药学杂志

OBJECTIVE: To discuss whether the difference in dissolution profile in vitro may cause different bioavailability in vivo and investigate the effects of the key quality parameters of leflunomide on bioavailability. METHODS: Using SANOFI product as the reference preparation and domestic product as the test preparation, the disintegration solution of leflunomide tablets was analyze by Morphologi G3-ID automated measurement to get the paricile size and size distribution of the API; using pH 6.5 FaSSIF solution without adding ox-gall sulfonic acid sodium and lecithin as the dissolution medium, the dissolution and permeation profiles of the reference and test preparations and raw material were compared at 37 ℃ with rotate speed of 150 r•min-1. The influence of quality parameters on the process of API's release and absorption was investigated, then the difference between the reference and test preparations were compared to preliminarily predict the bioavailability and bioequivalence. RESULTS: The particle size Dv(50)of domestic leflunomide tablets was 79.80 μm, while the particle size Dv(50)of the reference product was 17.60 μm; the dissolution rate and penetration rate of the test preparation were about 70% of the reference preparation, the tmax was basically identical,but the ρmax and AUC0-t were lower than the reference preparation. The bioavailability of the test preparation was about 90% of the reference preparation. CONCLUSION: Though the dissolution profile of domestic leflunomide tablets is not identical to the reference preparation, but the two products were predicted to be bioequivalent.

Leflunomide-induced Stevens Johnson syndrome in a patient with systemic lupus erythematosus / Síndrome de Stevens Johnson inducido por leflunomida en un paciente con lupus eritematoso sistémico

Abstract Leflunomide is an immunomodulatory agent widely used in rheumatoid arthritis and other rheumatic diseases like psoriatic arthritis and systemic lupus erythematosus. Although its safety profile is generally good, side effects have been reported in up to 20% of cases. Severe reactions, such as toxic epidermal necrolysis and Stevens Johnson syndrome are rare. The case is presented of a leflunomide-induced Stevens Johnson syndrome in a patient with systemic lupus erythematosus.

Resumen La leflunomida es un agente inmunomodulador de amplio uso en artritis reumatoide y también empleado en otras enfermedades reumáticas como artritis psoriásica y lupus eritematoso sistémico. Aunque su perfil de seguridad en general es bueno, se han reportado reacciones secundarias hasta en un 20%, aunque casos severos como necrólisis epidérmica tóxica y síndrome de Stevens Johnson son de muy baja frecuencia de presentación. Reportamos un caso de síndrome de Stevens Johnson inducido por leflunomida en una paciente con lupus eritematoso sistémico.

Clinical Efficacy and Safety of Tocilizumab on Rheumatoid Arthritis in 35 Cases / 医药导报

Objective To explore and compare the clinical curative effect of tocilizumab and leflunomide in the treatment of rheumatoid arthritis and to evaluate the safety. Methods From March 2015 to March 2016,70 cases of rheumatoid arthritis treated in the department of rheumatism in this hospital were divided into treatment group and control group by using a random number table method,35 cases in each group.The patients in the observation group were intravenously treated with tocilizumab,at dosage of 8 mg·kg-1,once every four weeks.The control group was treated by oral administration of leflunomide tablets,at 50 mg·d-1from the 1st to 3rd day,and at 20 mg·d-1from the fourth day to the end of the treatment.The treatment period was 24 weeks in the two groups.Joint swelling,joint pain,morning stiffness,ESR,CRP,IL-6 and IL-8 were recorded and compared before and during the treatment.Total effective rate of treatment was compared between the two groups.Adverse drug reaction was recorded and the incidence of adverse drug reactions was compared. Results After the treatment,joint swelling, joint pain,morning stiffness,ESR,CRP,IL-6 and IL-8 were significantly lower in the treatment group than those in the control group (P<0.05).After the treatment,the total effective rate of the treatment was significantly higher than that of the control group (P<0.05).After the treatment,incidence of adverse reaction was significantly lower in the treatment group than that in the control group(P<0.05). Conclusion Tocilizumab and leflunomide has certain curative effect in the treatment of rheumatoid arthritis, but tocilizumab is more effective,with low incidence of adverse reaction and a high clinical value.

Clinical observation and nursing intervention of prednisone acetate combined with leflunomide in the treatment of IgA nephropathy / 中国生化药物杂志

Objective To study and analyze the clinical observation and nursing measures of prednisone acetate combined leflunomide in the treatment of IgA nephropathy.Methods 100 patients with IgA nephropathy treated in our hospital from February 2015 to September 2016 were randomly divided into the control group and the experimental group,with 50 patients in each group.Patients in the control group were treated with prednisone and dropped to 0.5 mg/kg after 12 weeks.The patients in the experimental group were treated with leflunomide and dropped to 20 mg after 3 days.The patients in the experimental group and the control group were treated for 3 months.The two groups of patients were given reasonable nursing measures, and compared the treatment effect.Results The effective rate of treatment in the experimental group was 94.0％, significantly higher than that in the control group (64.0％),with statistical difference(P<0.05).After treatment,the level of 24 hours proteinuria in the experimental group was (0.541±0.322)g/L, significantly lower than that of the control group (1.516±0.568)g/L,with statistical difference (P<0.05) .The adverse reaction rate of the experimental group was 0％, and that of the control group was 8％,with statistical difference(P<0.05).Conclusion Prednisone acetate combined leflunomide was effective in the treatment of IgA nephropathy, and can significantly improve the efficiency of treatment, and has clinical significance.

Clinical Observation of Enhanced Immunosuppressive Therapy in the Treatment of Refractory Nephrotic Syndrome / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of enhanced immunosuppressive therapy in the treatment of refractory nephrotic syndrome (RNS). METHODS:Totally 76 RNS patients were selected from 2 hospitals during Jan. 2012-Mar. 2015,and then divided into control group and observation group according to random number table,with 38 cases in each group. Two groups were given Prednisone acetate tablet 50 mg,qd;decreasing to 15 mg,qd,after urine protein returned to normal. Based on it,control group was given Leflunomide tablets 50 mg,qd;decreasing to 20 mg,qd,3 days later. Based on con-trol group,observation group was additionally given Mycophenolate mofetil dispersible tablet 750 mg,bid;decreasing to 500 mg, qd,3 months later. Both groups were treated for 6 months. Clinical efficacies,follow-up recurrence rate as well as renal function in-dexes and inflammatory cell factors before and after treatment,and the occurrence of ADR were compared between 2 groups. RE-SULTS:The total response rate of observation group(92.11%)was significantly higher than control group(73.68%),and fol-low-up recurrence rate(5.26%)was significantly lower than control group(23.68%),with statistical significance(P0.05). After treatment,24 h urinary protein quantification,urinary IL-6 and IL-8 levels of 2 groups decreased significantly,while the content of serum protein increased significantly;the observation group was significantly better than the control group,with sta-tistical significance(P0.05). The incidence of ADR in the control group and the observation group was 34.21% and 44.74% respec-tively,without statistical significance between 2 groups(P>0.05). CONCLUSIONS:Enhanced immunosuppressive therapy in the treatment of RNS can improve renal function,reduce inflammatory reaction and long-term recurrence risk,and have good therapeu-tic efficacy and safety.