Use Of Leflunomide Research Articles

Use of Leflunomide for Treatment of Cytomegalovirus Infection in Recipients of Allogeneic Stem Cell Transplant.

Cytomegalovirus (CMV) reactivations are common after allogeneic stem cell transplants, and pre-emptive therapy has been found to be effective. However, in India, treatment options are limited because of high cost and toxicity of ganciclovir and unavailability of cidofovir and foscarnet. Leflunomide is a cheap and easily available anti-rheumatoid arthritis drug that has been shown to have anti-CMV properties both in vitro and in vivo. It also has been used effectively for CMV reactivation after renal transplants. In this retrospective analysis, we analyzed 70 allogeneic stem cell transplants that were conducted between April 2015 and February 2017. There were 49 episodes of CMV reactivations in 43 patients in this period. Leflunomide was used in 24 episodes. It was effective in CMV clearance in 9 of the 24 episodes (38%). When the CMV copy number was <2 × 103 copies/mL, leflunomide was effective in 9 of 17 (53%) episodes, but when the copy number was >2 × 103, leflunomide was ineffective in all of the 7 episodes. This difference was statistically significant (P= .022 by Fisher exact test), suggesting that leflunomide may be more effective in clearance of CMV when copy numbers are low.

BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non-kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV-DNAemia monthly until month 9, and then every 3months until 2years posttransplant. Extended screening after 2years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV-DNAemia of >1000copies/mL sustained for 3weeks or increasing to >10000copies/mL reflecting probable and presumptive BKPyV-associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy-proven BKPyV-associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV-DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine-A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV-DNAemia is definitively cleared, independent of failed allograft nephrectomy.

Intra-articular leflunomide-loaded poly(ε-caprolactone) implants to treat synovitis in rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune pathology that manifests as chronic inflammatory arthropathy and synovitis. Treatment of rheumatoid arthritis is based on the administration of different types of drugs, including leflunomide, an antirheumatic drug. However, the long-term systemic use of leflunomide may be associated with adverse effects. Local therapy could be an efficient strategy to treat synovitis triggered by rheumatoid arthritis without inducing adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) implants (leflunomide PCL implants) were evaluated as local drug delivery systems capable of attenuating inflammation and angiogenesis, which represent events of synovitis. Leflunomide PCL implants were designed by hot molding technique; and they were characterized by FTIR and DSC. These analytical techniques demonstrated the chemical integrity and dispersion of drug into the polymeric chains. Then, a spectrophometric method was developed and validated to quantify the leflunomide incorporated into the PCL implants and released from them. Linearity was obtained by ordinary least squares regression method to estimate the linear regression equation. Residues were evaluated considering normality, independence and homoscedasticity. Precision was lower than 5 %, and accuracy ranged from 98 to 104.5 %. Quantitation limit was 2.0 μg mL-1. PCL implants provided controlled and sustained release of leflunomide for 30 consecutive days after inserting these systems in the subcutaneous tissue of mice. The main mechanisms of drug delivery were solubilization and diffusion from polymer. Then, a non-biocompatible sponge was inserted into the subcutaneous tissue of mice to function as a frame to develop the inflammatory and angiogenic processes. Leflunomide PCL implants were inserted in direct contact with the sponge. At 4, 7 and 10 days after-sponge implantation, the key components of inflammatory angiogenesis were measured to verify the regression of these events induced by drug. Leflunomide controlled released from polymeric implants downregulated the neutrophil and monocyte/macrophage infiltration due to the reduced expression of myeloperoxidase (MPO) and N-acetyl-β-d-glucosaminidase (NAG), respectively. As the influx of these pro-inflammatory cells was modulated by leflunomide, the production of nitric oxide (NO), a pro-inflammatory substance, reached low concentrations in the sponge. As a consequence of the modulation of inflammation at the pathological site, the angiogenic process was downregulated, since the hemoglobin levels in the sponge were drastically reduced. The accumulation of leflunomide in the pathological site did not induce nephrotoxicity or hepatototoxicity, as confirmed by histological analyses. Finally, intra-articular leflunomide PCL implants represent a potential therapeutic alternative to treat locally the synovitis triggered by rheumatoid arthritis without inducing systemic adverse effects.

Combination of leflunomide and benazepril reduces renal injury of diabetic nephropathy rats and inhibits high-glucose induced cell apoptosis through regulation of NF-κB, TGF-β and TRPC6

Objective: To investigate effects of combination use of leflunomide and benazepril on diabetic nephropathy (DN) both in vivo and in vitro.Methods: The streptozotocin (STZ) induced Sprague-Dawley rats were treated with leflunomide (15 mg/kg/d), benazepril (15 mg/kg/d) or both the two drugs. Fasting blood glucose (FBG) and renal function indexes including blood urea nitrogen (BUN), serum creatinine (Scr), and proteinuria and kidney/body weight ratio (KW/BW) were measured. HE staining was used for histological analysis. The rat glomerular mesangial cells (RMCs) were treated with high-glucose (150 mg/ml) and the leflunomide and benazepril with both concentrations of 50 μmol/l were used to treat the high-glucose induced cells. TUNEL assay was used for measurement of cell apoptosis. Western blotting was conducted to determine expression of nuclear factor Kappa B (NF-κB), transforming growth factor-β (TGF-β) and transient receptor potential canonical 6 (TRPC6).Results: The body weight was significantly lower and all indexes of FBG, BUN, Scr, proteinuria and KW/BW ratio, GFR, as well as inflammatory factors TNF-α and IL-6 were significantly increased in the DN group after STZ treatment for 4 weeks. The treatment with leflunomide, benazepril or the both dramatically reduced the above effects induced by STZ, and the alteration was the most significant in the combination group. Treatment of leflunomide and benazepril significantly reduced expression levels of NF-κB, TGF-β and TRPC6 in renal tissues of DN rats as well as in high-glucose induced RMCs. It was also observed leflunomide and benazepril reduced high-glucose induced cell apoptosis of RMCs.Conclusion: The combination use of leflunomide and benazepril could improve the renal function and reduce the renal injury of DN rats and could reduce the levels of NF-κb, TGF-β and TRPC6 in both DN rats and high-glucose induced RMCs.

Effectiveness and Drug Survival of Anti-Tumor Necrosis Factor α Therapies in Patients With Spondyloarthritis: Analysis From the Thai Rheumatic Disease Prior Authorization Registry.

This study aimed to evaluate the long-term effectiveness and safety of the first anti-tumor necrosis factor α therapy (TNFi) and to identify the associated factors of drug discontinuation in patients with spondyloarthritis. This was a medical records review study. Patients with spondyloarthritis who were prescribed the first TNFi between December 2009 and October 2014 in the Rheumatic Disease Prior Authorization registry were enrolled. Baseline clinical data were retrieved. The Cox proportional hazards model was used to identify factors associated with discontinuation of drugs. Among 138 patients, 97 had ankylosing spondylitis (AS), and 41 had psoriatic arthritis (PsA). The effectiveness of TNFi in AS and PsA was 55% to 59% at 4 months and 75% to 96% at 3 years, as measured by a 50% decrease in the Bath Ankylosing Spondylitis Disease Activity Index from baseline. For PsA with peripheral arthritis, improvement of the joint count by 50% was observed in 61.8% of patients at 4 months and 100% at 3 years. Survival from TNFi was 63% for AS and 56% for PsA at 3 years. For AS, the factors associated with good response leading to discontinuation of TNFi were baseline patient global assessment 3 to 6/10 (hazard ratio [HR], 6.3) and the use of leflunomide (HR, 6.0) and infliximab (HR, 4.8). A good response (38.5%) was the most common cause of discontinuation of the first TNFi, followed by toxicity (28.2%), nonadherence (20.5%), and lack of effectiveness (12.8%). Ankylosing spondylitis and PsA responded well to TNFi during the 3-year follow-up. The retention rate was approximately 60% for AS and PsA. A good response to the first TNFi was the most common reason for discontinuation.

Biologics: a target therapy of lupus nephritis: a systematic review

Objective To review the use of biological management of lupus nephritis (LN). Data sources A systematic review of Medline (PubMed, Medscape, Science Direct, and EMF-Portal) and Internet was conducted on all articles published from 2006 to 2017. Study selection English-language reports on biological management of LN were searched. The initial search presented 150 articles, where 30 satisfied the inclusion criteria. Data extraction Articles not reporting on biological management of LN in the title or abstract were not included. A total of five independent investigators extracted data on methods. Data synthesis Comparisons were made by structured review, with the results tabulated. Overall, seven studies were about traditional therapy, 14 about biological therapy, and seven about evidence-based treatment for LN. Findings The various biological agents consisted of anti-B-cell therapies targeting either B-cell surface antigens or B-cell survival factors, anticytokines antibodies, and novel drugs intervening in B-T cell costimulation. Use of leflunomide in LN was found to be equally efficacious and safe at least in short term and in refractory LN. Immunosuppressive treatment should be guided by renal biopsy, and treatment aimed at complete renal response. Conclusion Biologicals, especially rituximab, although still off the shelf as an induction agent, can be used for resistant LN. Overall, treatment has to be individualized, multidisciplinary, and holistic to prevent loss-of-organ function.

New England BK consortium: Regional survey of BK screening and management protocols in comparison to published consensus guidelines.

BK polyomavirus (BKPyV) continues to impact renal transplant recipients (RTR). The New England BK Consortium aims to jointly optimize screening and management of BKPyV. Our first project was to survey centers' BKPyV screening protocols and compare them to consensus guidelines. Thirteen of 15 centers (86.7%) returned the survey. Only two center reported using monitoring parameters that were in line with consensus guidelines for BKPyV screening, while the majority of centers reported less intensive methods and shorter duration. One center reported performing renal biopsies in all patients with plasma viral loads >10000 copies/mL, while all other centers only perform for-cause biopsies. For presumptive nephropathy, 11 centers recommend a biopsy for confirmation. For management of documented BKPyV-associated nephropathy, 12 centers propose further immunosuppression reduction. Nine centers report CNI dose reduction as their primary treatment. More than half of centers surveyed reported use of leflunomide, cidofovir or intravenous immunoglobulin. There was a large variance in BKPyV screening and management strategies among centers. Due to these results, all participating centers agreed to implement uniform screening and aim to optimize management protocols.

Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis Is Associated With Changes in Blood Pressure.

This study reports the effect of disease-modifying therapies for rheumatoid arthritis (RA) on systolic and diastolic blood pressure (SBP, DBP) over 6 months and incident hypertension over 3 years in a large administrative database. We used administrative Veterans Affairs databases to define unique dispensing episodes of methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, tumor necrosis factor inhibitors, and prednisone among patients with RA. Changes in SBP and DBP in the 6 months before disease-modifying antirheumatic drug initiation were compared with changes observed in the 6 months after initiation. The risk of incident hypertension within 3 years (new diagnosis code for hypertension and prescription for antihypertensive) was also assessed. Multivariable models and propensity analyses assessed the impact of confounding by indication. A total of 37,900 treatment courses in 21,216 unique patients contributed data. Overall, there were no changes in SBP or DBP in 6 months prior to disease-modifying antirheumatic drug initiation (all P > 0.62). In contrast, there was a decline in SBP (β = -1.08 [-1.32 to -0.85]; P < 0.0001) and DBP (β = -0.48 [-0.62 to -0.33]; P < 0.0001) over the 6 months following initiation. The greatest decline was observed among methotrexate and hydroxychloroquine users. Methotrexate users were 9% more likely to have optimal blood pressure (BP) after 6 months of treatment. Patients treated with leflunomide had increases in BP and a greater risk of incident hypertension compared with patients treated with methotrexate (hazard ratio, 1.53 [1.21-1.91]; P < 0.001). Blood pressure may improve with treatment of RA, particularly with methotrexate or hydroxychloroquine. Leflunomide use, in contrast, is associated with increases in BP and a greater risk of incident hypertension.

EFFICIENCY AND SAFETY OF LEFLUNOMIDE TREATMENT IN PATIENTS WITH PULMONARY SARCOIDOSIS

Patients who have contraindications to the prescription of GCs (glucocorticosteroids), or have developed serious side effects during treatment with GCs, as well as patients with resistance to GCs therapy, are prescribed immunosuppressants. The aim of the research - to study the efficacy of leflunomide monotherapy in patients with pulmonary sarcoidosis with contraindications to prescription or serious side effects of glucocorticosteroids. Fourteen patients with sarcoidosis of the respiratory system of stage II were examined – 12 women and 2 men aged 30 to 69 years. In 10 patients there were contraindications to the appointment of GCs (diabetes mellitus – 5, hypertension – 3, obesity – 1, exacerbation of gastric ulcer – 1), which caused the appointment of immunosuppressive therapy as a starting. In 4 cases, serious side effects of SCs were noted, requiring the drug to be abolished (osteoporosis – 3, steroid diabetes – 1). Leflunomide was administered at a dose of 20 mg per day, daily for 3 months. The evaluation of efficacy was carried out using computed tomography of the thoracic cavity organs, body plethysmography, spirometry and determination of the diffusivity of the lungs. Monotherapy with leflunomide in patients with contraindications to prescription or serious side effects of GCs was successful in 7 out of 13 patients, in 2 patients there was a stabilization of the process, in 4 patients with leflunomide therapy progression of the disease was noted and in 1 case the treatment was discontinued due to serious side effects of preparation. The results obtained make it possible to recommend the use of leflunomide as monotherapy in patients with pulmonary sarcoidosis with contraindications to the prescription and/or poor tolerability of GCs and methotrexate. It is necessary to continue studying the possibilities of combined use of leflunomide with other drugs of the first line.

Leflunomide use in pregnancy: no increased risk of AEs

Leflunomide use in pregnancy: no increased risk of AEs

Experience with leflunomide as treatment and as secondary prophylaxis for cytomegalovirus infection in lung transplant recipients: A case series and review of the literature.

Data concerning the use of leflunomide-a drug approved for rheumatoid arthritis with in vitro anticytomegalovirus (CMV) activity-in lung transplant (LT) recipients are scarce. To report the use of leflunomide in LT recipients diagnosed with CMV infection/disease. We performed a single-center retrospective study including LT recipients who received leflunomide for CMV infection or as secondary prophylaxis after viremia clearance. We also conducted a full systematic PubMed search until June 30, 2017. We identified 5 LT recipients in our center plus 7 patients reported in the literature. All patients had previously received ganciclovir (GCV) and foscarnet (FOS), with drug-induced adverse effects described in 6 recipients (50%). Antiviral resistance mutations were observed in 8 patients (66.7%). Leflunomide was prescribed for CMV infection in 9 of 12 patients (75%) and as secondary prophylaxis in 3 patients (25%). Initial decrease of CMV viremia after starting leflunomide was observed in 7 of 9 recipients (77.7%), although this response was only transient in 2 patients. Long-term suppression of CMV viremia was reported in 7 of 12 patients (58.3%). In 3 recipients (25%), leflunomide was discontinued due to adverse effects. Our study has some limitations, such as the small number of patients included, its retrospective nature, and absence of leflunomide drug monitoring in serum. Notwithstanding, in our experience, leflunomide proved to be particularly effective as an anti-CMV secondary prophylaxis treatment and for clearing low-grade viremia. Moreover, leflunomide combined with a short course of GCV or intravitreal FOS also proved to be very effective in some patients. Leflunomide, alone or in combination, could be an effective treatment in selected LT recipients with GCV-resistant CMV infection and as secondary prophylaxis. Further studies are necessary.

Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes

ObjectivesLeflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. We quantified the risk of major congenital malformation (MCM), prematurity, low birth weight...

A Retrospective Study on the Safety and Efficacy of Leflunomide in Dogs.

BackgroundLittle clinical information is available concerning the use of leflunomide in dogs with immune‐mediated diseases.ObjectivesTo report the safety and efficacy of leflunomide for the treatment of naturally occurring immune‐mediated diseases in dogs.AnimalsNinety‐two dogs treated with leflunomide for management of suspected immune‐mediated diseases.MethodsRetrospective medical record review from Jan 1995 to Dec 2014. Data that were extracted from the medical records included signalment, body weight, underlying indication for leflunomide, dosage of leflunomide, treatment duration, concurrent medications, treatment response, and adverse events.ResultsAdverse events that could be related to leflunomide administration included diarrhea (3 of 92, 3.3%), lethargy (2 of 92, 2.2%), unexplained hemorrhage (3 of 92, 3.3%), thrombocytopenia (2 of 31, 6.5%), and increased liver enzyme activities (1 of 16, 6.3%). Significant dose differences between dogs with adverse events (n = 11; median, 2.9 mg/kg/d; range, 1.8–3.6 mg/kg/d) and dogs without adverse events (n = 81; median, 1.6 mg/kg/d; range, 0.8–4.3 mg/kg/d) were found (P < 0.001). Treatment response could be evaluated in 17 dogs. Of these 17 dogs, 12 dogs (70.5%) had an apparent positive response to the use of leflunomide. There was no significant difference (P = 0.22) in dosages between dogs that responded to leflunomide (n = 12; median, 1.9 mg/kg/d; range, 1.0–3.5 mg/kg/d) and those that did not respond (n = 5; median, 1.7 mg/kg/d; range, 1.0–2.0 mg/kg/d).Conclusions and Clinical ImportanceResults suggest that the starting dosage of leflunomide should be 2 mg/kg/d rather than the currently suggested dosage of 3–4 mg/kg/d.

Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey.

Leflunomide is indicated for the treatment of adults with rheumatoid arthritis, yet is underutilized. Given the cost of biologic therapy, understanding real-life effectiveness, safety, and sustainability of leflunomide, particularly in patients who have failed methotrexate, would be of value. The primary objective was to assess the proportion of patients achieving clinically meaningful benefit following an adequate trial of leflunomide. A retrospective analysis of a cohort supplemented with patient self-reported data using a standardized questionnaire. Data were analyzed using descriptive statistics, with a database multivariate logistic regression analysis to determine predictors of leflunomide response. Of the cohort available (N=2591), 1671 patients with confirmed leflunomide use were included in the retrospective analysis, of whom 249 were incident users. Low disease activity (DAS-28<3.2) was achieved or maintained by 20% of incident users, with 19% achieving a clinical response (DAS-28 decrease ≥1.2) at 3months. Adverse effects (AE) were reported by 29% of incident users and after 1year, 45% remained on leflunomide. Achievement of "minimal or no joint symptoms" was reported by 34% in the 661 analyzable survey responses (39% response rate). AE were reported by 55%, with nuisance (hair loss, nausea, stomach pain) AE and diarrhea being most common. Leflunomide was discontinued by 67% of responders within 1year. An important proportion of patients, the majority of whom had previously failed methotrexate, achieved disease response with leflunomide with a low risk of serious adverse effects, suggesting that a trial of leflunomide may be a reasonable and cost-effective strategy prior to biologic therapy.

Incidence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study

ObjectivesTo examine the incidence and temporal trends of psoriatic arthritis (PsA) in the general population in Denmark.MethodsUsing nationwide registry data, we estimated the number of patients with incident PsA within...

Leflunomide in the Treatment of a Pseudotumoral Genital Herpes Simplex Virus Infection in an HIV Patient

The patient is a 52-year-old African American man with a past medical history of HIV infection (on antiretroviral therapy, CD4 count 399 cells/µL, and undetectable HIV viral load) and recurrent genital herpes. While on valacyclovir, the patient presented with four tumorous lesions on the perineum and scrotum. A biopsy specimen stained positively with HSV-1 and HSV-2 immunostains and displayed a lymphoplasmacytic infiltrate. The patient received foscarnet and imiquimod for two weeks with minimal improvement. Based on the previous activity of leflunomide, which has both antiviral and immunomodulatory properties, in cytomegalovirus and herpes simplex infections, leflunomide 20 mg orally twice daily was started. The patient received 23 days of foscarnet, 14 days of topical imiquimod, and 11 days of leflunomide with approximately 80% reduction in the size of the perineal lesion. After nine months on leflunomide there was complete regression of the large perineal lesion and only two small ulcerations remained on the scrotum. Pseudotumoral herpes lesions in HIV patients represent an immune reconstitution event and are poorly responsive to the usual anti-herpes agents. This report demonstrates the successful use of leflunomide in the treatment of an HIV patient with pseudotumoral herpes. Thalidomide has also been used with some success.

Putting recommendations into practice: Australian rheumatologists' opinions on leflunomide use in rheumatoid arthritis.

Leflunomide is the most recently introduced conventional disease-modifying anti-rheumatic drugs in Australia. It has several unique methods for initiation, unique monitoring recommendations and a distinctive cessation protocol in the event of serious toxicity. The aim of this study was to evaluate initiation and monitoring practices of Australian rheumatologists using leflunomide. A survey was emailed twice, approximately 3months apart to 332 rheumatologist members of the Australian Rheumatology Association. Wave analysis was used to assess evidence of non-response bias. The response rate to the survey was 20% and there was no difference between the responses of waves 1 and 2. Fifty percent of the respondents indicated that 20mg once daily was the initial dose of leflunomide that they most commonly prescribed, 45% indicated 10mg once daily, whilst only 3% preferred to initiate leflunomide at 100mg daily for 2-3days followed by 10mg once a day as recommended when first marketed. Of the responders, 12% had used doses above 20mg daily and 70% had used alternate daily dosing with leflunomide. In a patient taking leflunomide with an ALT or AST >3 times the ULN on two or more blood tests, 75% of responders indicated they would stop leflunomide immediately and 20% would follow cessation by administering a cholestyramine washout. The choice of initial leflunomide dose among responding Australian rheumatologists varied considerably, although most preferred not to use the loading dose. Despite the recommendation of clinical guidelines, the use of a cholestyramine washout procedure for hepatic toxicity is not universal.

Diarrhea: Always Keep an Open Mind and Be a Skeptic

Background: Microscopic colitis is a well-known cause of chronic diarrhea and, when drug-related, is usually from proton pump inhibitors or non-steroidal anti-inflammatory drugs. To date, only 3 reports have been published on microscopic colitis from leflunomide. Here, we describe the first case of microscopic colitis associated with leflunomide use in North America. Case: description A 48-year-old woman with rheumatoid arthritis (RA) on leflunomide, was sent to our medical center for evaluation of chronic watery, non-bloody diarrhea. The diarrhea started 2 years prior and she described 8-16 episodes daily. Initial colonoscopy and histology were interpreted as ischemic colitis. Trials of prednisone and mesalamine yielded no improvement. Adalimumab, given for RA, resulted in transient improvement in diarrhea. One year later, while the patient was on adalimumab, diarrhea intensified and became associated with malaise and weight loss of 20 lb. Budesonide was added by her gastroenterologist but both adalimumab and budesonide were eventually discontinued due to lack of response. Repeat colonoscopy showed colitis sparing the rectum and again histology was interpreted as ischemic colitis. Magnetic resonance arteriography showed only age-related non-obstructive vascular changes. Upon referral, the patient noted spontaneous improvement in diarrhea; she was having 2-3 bowel movements a day and her only medication was leflunomide. Family history was notable for her brother having Crohn's disease. Physical exam and blood tests, including prometheus® inflammatory bowel disease and celiac panels were unremarkable. Repeat colonoscopy was unremarkable but biopsy specimens from the transverse and left colon showed collagenous colitis. Review of the prior biopsies by a GI pathologist showed collagenous colitis, albeit more severe than the pattern seen on last colonoscopy. The patient's diarrhea resolved after discontinuation of leflunomide. Conclusion: This is the first case report of leflunomide-related collagenous colitis in North America. Gastroenterologists and pathologists should have a high index of suspicion for microscopic colitis in patients with chronic non-bloody diarrhea even if they are not on medications recognized to cause microscopic colitis. Finally, it is always important to have an experienced pathologist review prior histologic material to avoid misdiagnosis.

Nefritis túbulo intersticial por leflunomida

The link between renal Tubule Interstitial Nephritis and the use of Leflunomide has not been described in the literature yet, this drug is not recognized as a nephrotoxic; therefore tracking renal function is not usually performed. We report the case of a patient admitted to the University Hospital of Clinic San Rafael by non-specific clinical symptoms and rapid deterioration of renal function. After ruling out the usual causes, we performed a renal biopsy, documenting the presence of severe tubule interstitial nephritis. By the time the use of Leflunomide was the only unusual precedent. After we suspended the treatment, the patient showed full recovery of the renal function. It is our intention to describe this case to highlight the connection between renal Tubule Interstitial Nephritis and the use of Leflunomide in order to promote keeping track of similar cases.

Leflunomide Use and Risk of Lung Disease in Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis of Randomized Controlled Trials.

To evaluate the relative risk (RR) of pulmonary disease among patients with rheumatoid arthritis (RA) treated with leflunomide (LEF). We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to April 15, 2014. We included double-blind randomized controlled trials (RCT) of LEF versus placebo or active comparator agents in adults with RA. Studies with fewer than 50 subjects or shorter than 12 weeks were excluded. Two investigators independently searched both databases. All authors reviewed selected studies. We compared RR differences using the Mantel-Haenszel random-effects method to assess total respiratory adverse events, infectious respiratory adverse events, noninfectious respiratory adverse events, interstitial lung disease, and death. Our literature search returned 5673 results. A total of 8 studies, 4 with placebo comparators, met our inclusion criteria. There were 708 respiratory adverse events documented in 4579 participants. Six cases of pneumonitis occurred, all in the comparator group. Four pulmonary deaths were reported, none in the LEF group. LEF was not associated with an increased risk of total adverse respiratory events (RR 0.99, 95% CI 0.56-1.78) or infectious respiratory adverse events (RR 1.02, 95% CI 0.58-1.82). LEF was associated with a decreased risk of noninfectious respiratory adverse events (RR 0.64, 95% CI 0.41-0.97). Our study found no evidence of increased respiratory adverse events in RCT of LEF treatment.