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1.
RMD Open ; 10(1)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38443091

RESUMEN

OBJECTIVE: This study aims to evaluate the effectiveness and safety of adalimumab (ADA) compared with leflunomide (LEF) in patients with Takayasu arteritis (TAK). METHOD: A retrospective cohort study was performed with the following inclusion criteria: the fulfilment of the 2022 American College Classification/European Alliance of Associations for Rheumatology criteria for TAK, age ≥18 years, and written informed consent. Forty-four patients were treated with LEF (n=28) or ADA (n=16) therapy due to relapsing/refractory disease or toxicity from previous therapy. Patients were evaluated at baseline (T0), at a median of 7.0 months (T1) and at 15.0 months of follow-up (T2). Data regarding disease activity, daily dose of prednisone, side effects and angiographic progression were analysed. RESULTS: LEF and ADA groups had similar features on the baseline visit. However, intravenous methylprednisolone was more frequently prescribed for the ADA group (p=0.019). On T1 and T2 visits, complete response rates were similar for ADA and LEF groups (75.0% and 88.5%; p=0.397 and 62.5% vs 78.3%; p=0.307), respectively. The differences remained non-significant after adjusting for baseline variables by propensity score matching. Although the ADA group had a higher median daily prednisone on visit T1 (p=0.004), it was similar on visit T2 (p=0.595). Similar rates of angiographic progression were observed in ADA and LEF groups (40% vs 25%; p=0.467). Mild-to-moderate adverse events were observed only in the LEF group (17.9%). CONCLUSION: LEF and ADA had comparable outcomes after a median of 15.0 months of follow-up. However, withdrawal from therapy and mild-to-moderate adverse events were only observed in the LEF group.


Asunto(s)
Arteritis de Takayasu , Humanos , Adolescente , Arteritis de Takayasu/diagnóstico , Arteritis de Takayasu/tratamiento farmacológico , Adalimumab/efectos adversos , Leflunamida/efectos adversos , Prednisona , Estudios Retrospectivos
2.
BMC Urol ; 24(1): 56, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468247

RESUMEN

BACKGROUND AND OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022361883.


Asunto(s)
Glomerulonefritis por IGA , Humanos , Leflunamida/efectos adversos , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/inducido químicamente , Inmunosupresores/efectos adversos , Corticoesteroides/uso terapéutico , Corticoesteroides/farmacología , Tasa de Filtración Glomerular
3.
Cochrane Database Syst Rev ; 2: CD003129, 2024 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-38334147

RESUMEN

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used disease-modifying antirheumatic drug (DMARD). This is an update of a 2001 Cochrane review. It supports a living guideline for children and young people with JIA. OBJECTIVES: To assess the benefits and harms of methotrexate for children and young people with juvenile idiopathic arthritis. SEARCH METHODS: The Australian JIA Living Guideline Working Group created a registry of all randomised controlled trials (RCTs) of JIA by searching CENTRAL, MEDLINE, Embase, and trials registries. The date of the most recent search of online databases was 1 February 2023. SELECTION CRITERIA: We searched for RCTs that compared methotrexate with placebo, no treatment, or another DMARD (with or without concomitant therapies) in children and young people (aged up to 18 years) with JIA. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The main comparison was methotrexate versus placebo. Our outcomes were treatment response, sustained clinically inactive disease, function, pain, participant global assessment of well-being, serious adverse events, and withdrawals due to adverse events. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified three new trials in this update, bringing the total number of included RCTs to five (575 participants). Three trials evaluated oral methotrexate versus placebo, one evaluated methotrexate plus intra-articular glucocorticoid (IAGC) therapy versus IAGC therapy alone, and one evaluated methotrexate versus leflunomide. Doses of methotrexate ranged from 5 mg/m2/week to 15 mg/m2/week in four trials, and participants in the methotrexate group of the remaining trial received 0.5 mg/kg/week. Trial size varied from 31 to 226 participants. The average age of participants ranged from four to 10 years. Most participants were females and most had nonsystemic JIA. The study that evaluated methotrexate plus IAGC therapy versus IAGC therapy alone recruited children and young people with the oligoarticular disease subtype of JIA. Two placebo-controlled trials and the trial of methotrexate versus leflunomide were adequately randomised and blinded, and likely not susceptible to important biases. One placebo-controlled trial may have been susceptible to selection bias due to lack of adequate reporting of randomisation methods. The trial investigating the addition of methotrexate to IAGC therapy was susceptible to performance and detection biases. Methotrexate versus placebo Methotrexate compared with placebo may increase the number of children and young people who achieve treatment response up to six months (absolute difference of 163 more per 1000 people; risk ratio (RR) 1.67, 95% confidence interval (CI) 1.21 to 2.31; I2 = 0%; 3 trials, 328 participants; low-certainty evidence). However, methotrexate compared with placebo may have little or no effect on pain as measured on an increasing scale of 0 to 100 (mean difference (MD) -1.10 points, 95% CI -9.09 to 6.88; 1 trial, 114 participants), improvement in participant global assessment of well-being (absolute difference of 92 more per 1000 people; RR 1.23, 95% CI 0.88 to 1.72; 1 trial, 176 participants), occurrence of serious adverse events (absolute difference of 5 fewer per 1000 people; RR 0.63, 95% CI 0.04 to 8.97; 3 trials, 328 participants), and withdrawals due to adverse events (RR 3.46, 95% CI 0.60 to 19.79; 3 trials, 328 participants) up to six months. We could not estimate the absolute difference for withdrawals due to adverse events because there were no withdrawals in the placebo group. All outcomes were reported within six months of randomisation. We downgraded the certainty of the evidence to low for all outcomes due to indirectness (suboptimal dosing of methotrexate and diverse outcome measures) and imprecision (few participants and low event rates). No trials reported function or the number of participants with sustained clinically inactive disease. Serious adverse events included liver derangement, abdominal pain, and inadvertent overdose. Methotrexate plus intra-articular corticosteroid therapy versus intra-articular corticosteroid therapy alone Methotrexate plus IAGC therapy compared with IAGC therapy alone may have little or no effect on the probability of sustained clinically inactive disease or the rate of withdrawals due to adverse events up to 12 months in children and young people with the oligoarticular subtype of JIA (low-certainty evidence). We could not calculate the absolute difference in withdrawals due to adverse events because there were no withdrawals in the control group. We are uncertain if there is any difference between the interventions in the risk of severe adverse events, because none were reported. The study did not report treatment response, function, pain, or participant global assessment of well-being. Methotrexate versus an alternative disease-modifying antirheumatic drug Methotrexate compared with leflunomide may have little or no effect on the probability of treatment response or on function, participant global assessment of well-being, risk of serious adverse events, and rate of withdrawals due to adverse events up to four months. We downgraded the certainty of the evidence for all outcomes to low due to imprecision. The study did not report pain or sustained clinically inactive disease. AUTHORS' CONCLUSIONS: Oral methotrexate (5 mg/m2/week to 15 mg/m2/week) compared with placebo may increase the number of children and young people achieving treatment response but may have little or no effect on pain or participant global assessment of well-being. Oral methotrexate plus IAGC injections compared to IAGC injections alone may have little or no effect on the likelihood of sustained clinically inactive disease among children and young people with oligoarticular JIA. Similarly, methotrexate compared with leflunomide may have little or no effect on treatment response, function, and participant global assessment of well-being. Serious adverse events due to methotrexate appear to be rare. We will update this review as new evidence becomes available to inform the living guideline.


Asunto(s)
Antirreumáticos , Artritis Juvenil , Niño , Femenino , Humanos , Adolescente , Anciano , Preescolar , Masculino , Metotrexato/efectos adversos , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/inducido químicamente , Leflunamida/efectos adversos , Australia , Antirreumáticos/efectos adversos , Glucocorticoides , Dolor/tratamiento farmacológico
4.
Clin Exp Dermatol ; 49(3): 247-254, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-37936305

RESUMEN

BACKGROUND: Pigmented contact dermatitis (PCD) is a noneczematous form of allergic contact dermatitis characterized by dermal hyperpigmentation. Allergen avoidance is the cornerstone of therapy, but it is difficult to achieve. The use of immunosuppressives seems rational, but data are lacking. OBJECTIVES: To compare outcomes with azathioprine (AZA), leflunomide and allergen avoidance (AA) in patients with PCD. METHODS: A comparative study was conducted on 28 patients with patch test-positive PCD who were randomly allocated to one of three treatment groups: AZA 2 mg kg-1 daily for 24 weeks + AA (n = 10); leflunomide (LEF) 20 mg daily for 24 weeks + -AA (n = 8); AA alone (n = 10). Patients were followed up for an additional 24 weeks. The Dermal Pigmentation Area and Severity Index (DPASI) score and Hindi Melasma Quality of Life scale (MELASQOL) were used to assess hyperpigmentation and quality of life (QoL). respectively. RESULTS: Hair colorants (n = 12) and paraphenylenediamine (n = 8) were the most common allergens. Mean (SD) DPASI score decreased from 30.97 (3.69), 32.35 (3.90) and 31.86 (3.47) to 13.78 (4.25), 21.67 (2.99) and 20.64 (3.82) at 48 weeks in the three groups, respectively (P < 0.001); the maximum percentage decline was seen with AZA (56%). Mean (SD) MELASQOL score was reduced in the three treatment groups from 48.0 (6.46), 46.75 (3.69) and 46.6 (4.65) to 19.6 (6.98), 24.5 (5.80) and 24.0 (5.49), respectively, at 48 weeks (P < 0.001). Reductions in DPASI and Hindi MELASQOL scores were significantly correlated. The most frequent adverse event was transaminitis in both the AZA and LEF groups. CONCLUSIONS: Patients on AZA achieved a statistically significantly greater reduction in DPASI and MELASQOL score; therefore, AZA may fulfil an unmet need in PCD treatment. An objective reduction in hyperpigmentation was paralleled by an improvement in QoL score, reiterating the need for active management of this disease.


Asunto(s)
Dermatitis Alérgica por Contacto , Melanosis , Humanos , Alérgenos , Azatioprina/efectos adversos , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/etiología , Leflunamida/efectos adversos , Pruebas del Parche , Calidad de Vida
5.
Clin J Gastroenterol ; 17(1): 65-68, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37796437

RESUMEN

We describe a patient with rheumatoid arthritis and Hashimoto's thyroiditis who developed chronic diarrhea and subsequently diagnosed with collagenous colitis (CC) 5 years after leflunomide initiation. Cessation of leflunomide resulted in complete resolution of diarrhea within 2 months. Although rare, leflunomide-induced colitis should be considered in patients with otherwise unexplained chronic diarrhea. Diagnosis is challenging as symptom onset can occur many years after leflunomide initiation, but diarrheal symptoms typically resolve within weeks to months of stopping the instigating drug.


Asunto(s)
Artritis Reumatoide , Colitis Colagenosa , Colitis , Humanos , Leflunamida/efectos adversos , Colitis Colagenosa/inducido químicamente , Colitis Colagenosa/complicaciones , Colitis/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Diarrea/inducido químicamente
6.
Exp Clin Transplant ; 22(1): 29-34, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38149668

RESUMEN

OBJECTIVES: BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients. MATERIALS AND METHODS: Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia. RESULTS: Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy. CONCLUSIONS: Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.


Asunto(s)
Virus BK , Enfermedades Renales , Trasplante de Riñón , Nefritis Intersticial , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Masculino , Niño , Femenino , Leflunamida/efectos adversos , Cidofovir/efectos adversos , Trasplante de Riñón/efectos adversos , Viremia/diagnóstico , Estudios Retrospectivos , Creatinina , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/tratamiento farmacológico , Enfermedades Renales/diagnóstico , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/cirugía , Nefritis Intersticial/complicaciones , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/tratamiento farmacológico , Receptores de Trasplantes
7.
Exp Clin Transplant ; 21(10): 814-819, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37965956

RESUMEN

OBJECTIVES: Nephropathy due to BK virus infection is a major cause of graft dysfunction and loss. No specific treatment has been developed for the BK virus. Here, we compared the combination of intravenous immunoglobulin and leflunomide versus intravenous immunoglobulin to treat BK virus nephropathy after renal transplant. MATERIALS AND METHODS: This study was a randomized controlled clinical trial. Sixteen kidney transplant patients with BK virus infection were randomly divided into 2 groups; 1 group received intravenous immunoglobulin, and another group received leflunomide and intravenous immunoglobulin. P < .05 was considered statistically significant. RESULTS: Results of a polymerase chain reaction test for BK virus after 2 months of treatment were negative in 3 patients in the intravenous immunoglobulin group and in 7 patients in the intravenous immunoglobulin + leflunomide group. The amount of BK virus decreased significantly in each group, and a significant difference was observed between the 2 groups after 3 months (P = .014). The average level of creatinine in the intravenous immunoglobulin group at 1, 2, and 3 months after treatment was 1.7 ± 0.23, 1.8 ± 0.5, and 1.5 ± 0.3, respectively, and in the intravenous immunoglobulin + leflunomide group was 2.1 ± 0.75, 1.76 ± 0.37, and 1.4 ± 0.18, respectively (P > .05). CONCLUSIONS: Although BK viral load decreased significantly in both groups, there was a significant difference between patients who received intravenous immunoglobulin versus those who received the combination of intravenous immunoglobulin + leflunomide after 3 months. The addition of leflunomide to the intravenous immunoglobulin treatment seems to have a better effect in reducing BK viral load. However, further studies with a larger sample and longer duration are needed.


Asunto(s)
Virus BK , Trasplante de Riñón , Nefritis Intersticial , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Leflunamida/efectos adversos , Trasplante de Riñón/efectos adversos , Inmunoglobulinas Intravenosas/efectos adversos , Inmunosupresores , Antivirales/uso terapéutico , Nefritis Intersticial/tratamiento farmacológico , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/tratamiento farmacológico
8.
Exp Clin Transplant ; 21(10): 826-830, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37965958

RESUMEN

OBJECTIVES: Infection with the BK virus is a significant complication after renal transplant and can progress to BK virus nephropathy and graft dysfunction. There is no consensus on the management of BK virus infection in pediatric renal transplant recipients. The most common therapeutic option is immunosuppression reduction, which can increase rejection risk. We aimed to examine the effect of leflunomide, an agent with antiviral and immunosuppressive actions, in a case series of pediatric renal transplant recipients with BK virus infection. MATERIALS AND METHODS: Routine screening with blood BK virus DNA polymerase chain reaction was performed regularly in all of our renal transplant patients. When BK virus was detected, we reduced tacrolimus levels, discontinued mycophenolate mofetil, and started active treatment with leflunomide. Treatment with leflunomide was continued until BK virus was undetectable by polymerase chain reaction in at least 2 blood samples 2 weeks apart. RESULTS: All pediatric patients developed BK virus infection in a mean period of 3.9 months after transplant. Graft dysfunction was evident in all patients with 20% to 100% elevation of creatinine from baseline. Afterleflunomide initiation, all patients had undetectable levels of BK virus by plasma polymerase chain reaction in at least 2 different samples within a mean period of 3.4 months, and renal function had normalized back to the baseline. None of our patients had evidence of hepatotoxicity or anemia on regular monitoring, with no other adverse events. Renal function remained stable in the follow-up period with no reoccurrence of BK viremia up to the date of this writing. CONCLUSIONS: Treatment with leflunomide resulted in rapid BK virus clearance and preservation of renal function with no adverse effects.


Asunto(s)
Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Niño , Leflunamida/efectos adversos , Trasplante de Riñón/efectos adversos , Riñón , Inmunosupresores/efectos adversos , Receptores de Trasplantes , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/tratamiento farmacológico
9.
PLoS One ; 18(8): e0290668, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37624868

RESUMEN

The constant use of disease modifying anti rheumatic drugs affects the functioning of multiple organs inside the body. Some drugs are more toxic than others. The present case control investigation was designed to evaluate the comparative toxicity of methotrexate and leflunomide on multiple organs in rheumatoid arthritis patients. For this purpose, 100 subjects with confirmed rheumatoid arthritis condition were recruited form tertiary care center. Whereas 50 age matched controls were recruited from the local healthy population. Participants of the study were categorized into three groups with equal numbers of subjects in each group (n = 50). Group 1 comprised rheumatoid arthritis patients on methotrexate treatment, group 2 included rheumatoid arthritis patients on leflunomide treatment and group 3 were healthy subjects. Cardiac and respiratory response was evaluated by monitoring blood pressure, pulse and breathing rate and spot oxygen saturation. Stress on liver was estimated by measuring change in liver enzymes (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) and total bilirubin. While, degree of renal impairment was assessed by calculating glomerular filtration rate, serum creatinine, urinary urea and uric acid. For statistical interpretation, data was subjected to independent student "t" test and analysis of variance (one way ANOVA) for mean variations. Both methotrexate and leflunomide elevated the systolic and diastolic blood pressure and pulse rate. Leflunomide maintained the oxygen saturation at 96.7%, whereas methotrexate exerted serious effect on spot oxygen saturation by reducing it significantly to 93.25% than healthy subjects. Hepatotoxicity manifested by sustained use of leflunomide was perceptible in this study group. Whereas, both methotrexate and leflunomide influenced renal function as indicated by marked increase in blood urea nitrogen (P = 0.001), serum creatinine (P = 0.007) and reduced glomerular filtration rate (P<0.0001). However, use of methotrexate demonstrated significant (P<0.0001) reduction in serum uric acid and urinary urea levels. Methotrexate is more injurious to heart, blood vessels and kidneys than leflunomide but it is less noxious to hepatic parenchyma. Contrarily, leflunomide usage is comparatively better option for respiratory, cardiovascular, and renal health but dangerous to liver. Thus, a single drug can't be prescribed for the treatment of rheumatoid arthritis for longer management of arthritis patients.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Insuficiencia Renal , Humanos , Metotrexato/efectos adversos , Leflunamida/efectos adversos , Ácido Úrico , Creatinina , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Urea
10.
BMC Neurol ; 23(1): 168, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37101279

RESUMEN

BACKGROUND: Teriflunomide, the active metabolite of leflunomide, is a disease-modifying therapy drug used for the treatment of multiple sclerosis (MS), yet the complications associated with this drug remain not fully understood. Here we present the rare case of a 28-year-old female MS patient who developed subacute cutaneous lupus erythematosus (SCLE) following teriflunomide treatment. Though SCLE has been reported to be associated with leflunomide, the current report represents the first documented evidence demonstrating SCLE as a potential teriflunomide treatment-related complication. Additionally, a literature review on the leflunomide-induced SCLE was conducted to emphasize the association of SCLE with teriflunomide, specifically amongst the female demographic with a preexisting autoimmune diathesis. CASE PRESENTATION: A 28-year-old female first presented with MS symptoms in the left upper limb along with blurred vision in the left eye. Medical and family histories were unremarkable. The patient exhibited positive serum biomarkers including ANA, Ro/SSA, La/SSB, and Ro-52 antibodies. Relapsing-remitting MS was diagnosed according to the 2017 McDonald's diagnostic criteria, and remission was achieved upon intravenous administration of methylprednisolone followed by teriflunomide sequential therapy. Three months post-teriflunomide treatment, the patient developed multiple facial cutaneous lesions. SCLE was subsequently diagnosed and was attributed to treatment-related complication. Interventions include oral administration of hydroxychloroquine and tofacitinib citrate effectively resolved cutaneous lesions. Discontinuation of hydroxychloroquine and tofacitinib citrate treatment led to recurring SCLE symptoms under continuous teriflunomide treatment. Full remission of facial annular plaques was achieved after re-treatment with hydroxychloroquine and tofacitinib citrate. The patient's clinical condition remained stable in long-term outpatient follow-ups. CONCLUSIONS: As teriflunomide has become a standard disease-modifying therapy for MS, the current case report highlights the importance of monitoring treatment-related complications, specifically in relation to SCLE symptoms.


Asunto(s)
Lupus Eritematoso Cutáneo , Esclerosis Múltiple , Humanos , Femenino , Adulto , Hidroxicloroquina/efectos adversos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Leflunamida/efectos adversos , Lupus Eritematoso Cutáneo/inducido químicamente , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/tratamiento farmacológico
11.
J Investig Med High Impact Case Rep ; 11: 23247096221150636, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36661254

RESUMEN

Immune-mediated necrotizing myopathy (IMNM) is a subtype of inflammatory myopathy that is characterized by proximal muscle weakness, markedly elevated serum creatine kinase, myopathic electromyographic findings, and muscle biopsies revealing necrosis or regeneration with sparse inflammatory infiltrate. IMNM tends to be idiopathic but has been associated with certain medications. This supports the possibility for other pharmacotherapies to induce IMNM-particularly leflunomide. Leflunomide is used in the treatment for rheumatoid arthritis and has been shown to induce autoimmune diseases-including autoimmune hepatitis and polymyositis. After an extensive review of history and workup of muscle weakness, we conclude that leflunomide induced an IMNM in our patient. As this is the first case of leflunomide-induced IMNM, it is important for clinicians to suspect an inflammatory myopathy in the setting of myositis while on leflunomide.


Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Miositis , Humanos , Leflunamida/efectos adversos , Músculo Esquelético/patología , Miositis/inducido químicamente , Miositis/complicaciones , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/complicaciones , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Debilidad Muscular
13.
Comput Math Methods Med ; 2022: 6829358, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36226244

RESUMEN

The present work is aimed at exploring the clinical efficacy and safety of methotrexate (MTX) and leflunomide (LEF) combination therapy for rheumatoid arthritis. From June 2019 to June 2021, a total of 120 individuals with rheumatoid arthritis received a diagnosis. Sixty patients each were randomly assigned to the control and observation groups. The observation group received MTX and LEF combo medication while the control group only received MTX treatment. Clinical efficacy, complication incidence, and the alleviation of inflammatory markers, joint pain, and clinical symptoms were compared between the 2 groups. Posttreatment, the observation group had overall response rate of 96.66%, while the control group had 86.67%, with significant differences. Compared with pretreatment, both control and observation group patients showed decreasing trends of IL-1 levels and increasing trends of IL-10 levels posttreatment, with significant differences (P < 0.05). Compared with the control group, patients in the observation group had lower IL-1 and TNF-α levels with significant differences (P < 0.05) and higher levels of IL-10 with significant difference (P < 0.05). In both groups, the pain score and the number of painful joints were much lower than they were prior to treatment. Following treatment, the observation group displayed significantly lower levels of erythrocyte sedimentation rate, rheumatoid factor, and C-reactive protein than the control group (P < 0.05). Clinical measures in the observation group were all lower than those in the control group with statistically significant differences (P < 0.05). Moreover, the incidence rate of adverse reactions showed no significant difference between these 2 groups (P > 0.05). In conclusion, the combination therapy of MTX and LEF is efficacious for rheumatic arthritis.


Asunto(s)
Artritis Reumatoide , Metotrexato , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Proteína C-Reactiva , Quimioterapia Combinada , Humanos , Interleucina-1/uso terapéutico , Interleucina-10/uso terapéutico , Leflunamida/efectos adversos , Metotrexato/efectos adversos , Factor Reumatoide , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa
14.
Ren Fail ; 44(1): 1011-1025, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35786300

RESUMEN

OBJECTIVE: We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of leflunomide combined with corticosteroids, compared with corticosteroids alone, for IgA nephropathy. MATERIALS AND METHODS: Studies were retrieved by searching of PubMed, Embase, Cochrane's Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases on 11 October 2021. A random-effect model incorporating the heterogeneity was used to pool the results. The efficacy outcomes included the complete remission rate of proteinuria, overall response rate (the combined rates of patients with complete and partial remission of proteinuria), changes of urine protein excretion (UPE), serum creatinine (SCr), and estimated glomerular infiltrating rate (eGFR). RESULTS: Nineteen studies were included. Patients receiving the combined therapy had a higher complete remission rate (relative risk [RR]: 1.29, 95% CI: 1.08-1.55, p = 0.006; I2 = 0%) and overall response rate (RR: 1.18, 95% CI: 1.10-1.26, p < 0.001, I2 = 0%) compared to patients who received CS alone. Besides, combined therapy was associated with significantly reduced levels of UPE (mean difference [MD]: -0.30 g/24h, 95% CI: -0.43 to -0.16, p < 0.001; I2 = 34%) and SCr (MD: -7.55 mmol/L, 95% CI: -11.06 to -4.04, p < 0.001; I2 = 34%), and increased level of eGFR (MD: 6.51 mL/min/1.73 m2, 95% CI: 4.06-8.97, p < 0.001; I2 = 0%). The incidence of adverse events was not significantly different. CONCLUSIONS: Combined treatment with leflunomide and corticosteroids was more effective than corticosteroids alone for patients with IgA nephropathy.


Asunto(s)
Glomerulonefritis por IGA , Corticoesteroides/efectos adversos , Glomerulonefritis por IGA/tratamiento farmacológico , Humanos , Leflunamida/efectos adversos , Proteinuria/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
Int J Rheum Dis ; 25(8): 893-896, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35666009

RESUMEN

OBJECTIVE: The goal of treatment in palindromic rheumatism (PR) is to control the attacks and prevent disease evolution to chronic arthritis. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including antimalarial and methotrexate cannot control attacks in all patients. METHODS: In this retrospective study, we assessed the efficacy of leflunomide in patients with PR who had an inadequate response to DMARDs. In this study, patients who had a diagnosis of PR and were treated with leflunomide because of active disease despite treatment with csDMARDs for at least 6 months were included. Remission was defined as no attacks for 3 months and prednisolone dose ≤5 mg/d. Leflunomide treatment failure was defined as failure to achieve remission, the need to add other DMARDs for controlling attacks and disease progression to chronic arthritis during treatment with leflunomide. RESULTS: Ten cases with active disease despite treatment with hydroxychloroquine and methotrexate and low-dose prednisolone treated with leflunomide were included in the study. During the 12.6 ± 7.5 months of treatment with leflunomide, the frequency of attacks significantly decreased. Complete and partial remission were achieved in 90% of patients. CONCLUSION: Our results indicate that leflunomide controls PR attacks and it might be a new option for patients with PR.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Quimioterapia Combinada , Humanos , Leflunamida/efectos adversos , Metotrexato/efectos adversos , Prednisolona/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
16.
Semin Arthritis Rheum ; 55: 152019, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35567808

RESUMEN

BACKGROUND: To compare infectious risk between leflunomide versus TNF inhibitors (TNFi), and between tacrolimus versus TNFi among rheumatoid arthritis (RA) patients receiving methotrexate (MTX). METHODS: Using Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating TNFi, leflunomide, or tacrolimus. The primary outcome was any serious infections defined as a composite endpoint of serious bacterial, opportunistic, and herpes zoster infections. Secondary outcomes were individual components of the primary outcome. Propensity-score fine-stratification (PSS) and weighting were applied to adjust for confounding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing leflunomide versus TNFi, and tacrolimus versus TNFi. RESULTS: Among 72,516 RA patients receiving MTX, we identified 3,336 TNFi initiators, 11,122 leflunomide initiators, and 5,136 tacrolimus initiators. Two study cohorts were 10,992 leflunomide initiators PSS-weighted on 1,623 TNFi initiators and 5,126 tacrolimus initiators PSS-weighted on 2,521 TNFi initiators. The incidence rate per 100 person-years of herpes zoster infection (3.70-4.27) was beyond 3-times that of serious bacterial infection (1.12-1.36), but opportunistic infection was relatively rare (0.11-0.23). The PSS-weighted HR [95% CI] for any serious infection was 1.03 [0.89-1.22] comparing leflunomide versus TNFi, and 0.91 [0.77-1.08] comparing tacrolimus versus TNFi. Analyses on the secondary outcomes showed consistent results. CONCLUSION: In this nation-wide cohort study, we did not find a significant difference in the risk of serious infections (i.e., serious bacterial, opportunistic, and herpes zoster infections) between leflunomide versus TNFi, and between tacrolimus versus TNFi among RA patients receiving background MTX.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Infecciones , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/epidemiología , Estudios de Cohortes , Herpes Zóster/inducido químicamente , Herpes Zóster/epidemiología , Humanos , Infecciones/epidemiología , Infecciones/etiología , Leflunamida/efectos adversos , Leflunamida/uso terapéutico , Metotrexato/uso terapéutico , Tacrolimus/efectos adversos , Tacrolimus/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico
17.
Int J Rheum Dis ; 25(6): 650-658, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35348297

RESUMEN

OBJECTIVES: To evaluate the effectiveness of leflunomide as a steroid-sparing agent among Indian patients with giant cell arteritis (GCA) and to assess the changes of "halo sign" within affected arteries, detected ultrasonographically, after remission. METHODS: In this prospective observational study, patients fulfilling American College of Rheumatology criteria for GCA and having halo sign in temporal artery ultrasound were treated with leflunomide and predefined tapering dose of prednisolone. Ultrasounds of temporal and axillary arteries were done at baseline and after remission were achieved. RESULTS: Twenty-two GCA patients were followed up for a median duration of 24 months (interquartile range, IQR: 18-33). All patients showed clinical improvement and steroids could be stopped in 17 out of 22 patients. Median time to achieve remission (symptom-free with normal inflammatory markers) was 3 (95% confidence interval [CI]: 2.4-3.6) months. Median time to achieve reduction to prednisolone dose <5 mg/d was 9 months (95% CI: 7-11). Prednisolone dose could be reduced in all patients while on leflunomide, suggesting steroid-sparing effect and a steroid-free remission could be achieved after a median of 14 months (95% CI: 9.4-18.6). Ultrasonographically, all patients showed improvement of halo signs, after 8 weeks (IQR 7.25-12). Seven patients experienced a clinical relapse after 12 months (IQR: 5-21) of initial remission. The predictors of relapse were duration of symptoms before initiation of immunosuppression therapy and delayed achievement remission by strict criteria. CONCLUSION: This study showed efficacy and safety of leflunomide as a steroid-sparing agent in Indian GCA patients.


Asunto(s)
Arteritis de Células Gigantes , Estudios de Seguimiento , Arteritis de Células Gigantes/diagnóstico por imagen , Arteritis de Células Gigantes/tratamiento farmacológico , Humanos , Leflunamida/efectos adversos , Prednisolona/efectos adversos , Recurrencia , Esteroides/uso terapéutico
18.
Sci Rep ; 12(1): 1877, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-35115601

RESUMEN

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Crotonatos/uso terapéutico , Hidroxibutiratos/uso terapéutico , Leflunamida/uso terapéutico , Nitrilos/uso terapéutico , Toluidinas/uso terapéutico , Adulto , Anciano , Antirreumáticos/efectos adversos , Antirreumáticos/sangre , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Estudios Transversales , Crotonatos/efectos adversos , Crotonatos/sangre , Monitoreo de Drogas , Quimioterapia Combinada , Femenino , Humanos , Hidroxibutiratos/efectos adversos , Hidroxibutiratos/sangre , Leflunamida/efectos adversos , Leflunamida/sangre , Masculino , Persona de Mediana Edad , Nitrilos/efectos adversos , Nitrilos/sangre , Valor Predictivo de las Pruebas , Inducción de Remisión , Índice de Severidad de la Enfermedad , Factores de Tiempo , Toluidinas/efectos adversos , Toluidinas/sangre , Resultado del Tratamiento
19.
Liver Int ; 42(6): 1323-1329, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35129282

RESUMEN

BACKGROUND: Leflunomide, a disease-modifying anti-rheumatic drug, has been associated with elevations of serum aminotransferases. Herein, we describe the clinical, laboratory features and outcomes of 17 patients with leflunomide/teriflunomide hepatotoxicity from two large drug-induced liver injury (DILI) registries. METHODS: Consecutive, adjudicated cases of leflunomide (n = 16)-or teriflunomide (n = 1)-related DILI from a single centre in Bangalore, India and the multicentre US Drug-Induced Liver Injury Network (DILIN) were reviewed. RESULTS: Nine (0.8%) of the 1070 Indian patients and 8 (0.5%) of the 1400 DILIN patients fulfilled the criteria for DILI because of leflunomide- or teriflunomide. 89% of the Indian cases were women and all were associated with severe cutaneous adverse reaction (SCAR) and a median drug latency of 49 days, whereas 37.5% of the DILIN cases were female, none exhibited SCAR and the median drug latency was 166 days. Hepatocellular injury (70%) was more common in women than men (92% vs. 20%) and was associated with younger mean age (41 vs. 59 years), higher peak INR (2.3 vs. 1.2) and higher mortality (58% vs. 0%). Mortality was observed in six patients from India (2 of the three with myocarditis) and one received liver transplantation from the USA. CONCLUSION: Leflunomide-induced liver injury is predominantly hepatocellular. Leflunomide hepatotoxicity is more likely accompanied by SCAR, a short latency and a higher mortality in the Indian cohort, with a predominance of females, compared to US DILIN patients. The differences in skin involvement, immunoallergic features and outcomes among subjects from India vs. the USA suggest that genetic or environmental factors are important in the pathogenesis of liver injury.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Difilina , Femenino , Humanos , India/epidemiología , Leflunamida/efectos adversos , Masculino , Sistema de Registros
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