Methotrexate Users Research Articles

Drug utilization patterns and adherence in patients on systemic medications for the treatment of psoriasis: A retrospective, comparative cohort study

Nonadherence to systemic treatments for psoriasis leads to treatment failure and increased health care utilization. Examine drug utilization patterns and adherence of new users of systemic medications for psoriasis. We conducted a retrospective, comparative cohort study using a large US health insurance claims database including psoriasis patients who were new users of acitretin, adalimumab, etanercept, methotrexate, or ustekinumab. Adherence was measured by using proportion of days covered dichotomized as adherent (≥0.80) or nonadherent (<0.80). Odds ratios (ORs) and 95% confidence intervals (CIs) comparing adherence to each exposure (acitretin, adalimumab, etanercept, or ustekinumab) to the referent (methotrexate) were estimated via logistic regression, with pairwise 1:1 propensity score matching to adjust for potential confounders. In total, 22,742 patients were new users of systemic medications. Among these patients, adherence to adalimumab (OR 2.24, 95% CI 2.05-2.45); etanercept (OR 1.77, 95% CI 1.63-1.92); and ustekinumab (OR 2.54, 95% CI 2.24-2.87) was greater and acitretin (OR 0.57, 95% CI 0.50-0.63) lower compared with methotrexate. Unable to evaluate reasons for discontinuation. We report greater adherence to biologics than methotrexate in new users. Further research is needed to understand overall low adherence to systemic medications for psoriasis.

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.

Long-term use of adalimumab as monotherapy after attainment of low disease activity with adalimumab plus methotrexate in patients with rheumatoid arthritis

ObjectiveTo evaluate long-term clinical, functional and radiographic outcomes in an open-label extension (OLE) study in patients with rheumatoid arthritis (RA) receiving adalimumab monotherapy or adalimumab+methotrexate following attainment of low disease...

Psoriatic patients with chronic viral hepatitis do not have an increased risk of liver cirrhosis despite long-term methotrexate use: Real-world data from a nationwide cohort study in Taiwan

Methotrexate (MTX) is commonly used in the treatment of patients with moderate-to-severe psoriasis. We conducted a nationwide population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic viral hepatitis-related cirrhosis among psoriatic patients in Taiwan. This study obtained data from the National Health Insurance Research Database in Taiwan. We identified 2417 psoriatic patients with chronic hepatitis B (CHB) (370 MTX users and 2047 nonusers of MTX) and 1127 psoriatic patients with chronic hepatitis C (CHC) (174 MTX users and 953 nonusers of MTX) from January 1, 2000, to December 31, 2010. After a mean follow-up of more than 9years since the diagnosis of chronic viral hepatitis, a total of 125 patients with CHB (5%) and 120 patients with CHC (11%) developed liver cirrhosis. Comparable proportions of MTX users and nonusers of MTX developed liver cirrhosis (4% vs 5% in patients with CHB and 11% vs 11% in patients with CHC [both P >.05]). There is possible selection bias and medication nonadherence. Our real-world data show that long-term MTX use may not be associated with an increasedrisk of liver cirrhosis among psoriatic patients with chronic viral hepatitis.

Therapeutic approach for the cesarean scar pregnancy.

The aim of this study was to explore the pros and cons of different treatments of cesarean scar pregnancy (CSP).We retrospectively studied 205 cases of CSP that were treated in our hospital from June 2013 to June 2014, 189 of which had surgical operation.The average age of the patients was (32.98 ± 4.56) years. Data from those 189 cases were analyzed.Two hundred five patients from Beijing Obstetrics and Gynecology Hospital.One hundred eighty-nine cases who had operative treatment, 111 of which received curettage under hysteroscopy, 70 of which received curettage under ultrasonography, 8 of which received laparoscopic Cesarean scar resection.Management of 189 ectopic Cesarean scar pregnancy cases discussed in this article was usage of methotrexate (MTX) via the utility of uterine arterial chemotherapy embolization (UACE).All of 189 patients were cured without hysterectomy. Hysteroscopy provides a clear view for us, making it easy to identify the range of affected tissues, and clean the pregnancy tissue. Curettage under ultrasonography is relatively simple and inexpensive. Laparoscopic surgery is more suitable for exogenous CSP patients that can reduce the operation risk and prevent uterine perforation. However, laparoscopic surgery costs much more than those 2 and needs longer time of hospitalization.Treatment options should be personalized according to different situations. Minimal invasion, thorough treatment, quick recovery, low risk of hysterectomy, preserved fertility function, and improved life quality are the principles we have been pursuing for.

The role of concomitant methotrexate dosage and maintenance over time in the therapy of rheumatoid arthritis patients treated with adalimumab or etanercept: retrospective analysis of a local registry.

ObjectiveTo evaluate the pattern of prescription and maintenance over time of concomitant methotrexate (MTX), and its impact on a 2-year clinical response in a cohort of rheumatoid arthritis (RA) patients treated with a first-line tumor necrosis factor alpha inhibitor (TNFi).Patients and methodsThe study population included all RA patients receiving adalimumab or etanercept a as first-line biologic drug, extracted from a local registry. Enrolled patients were stratified into 3 subgroups according to baseline concomitant MTX: no MTX, low-dose MTX (≤10 mg/wk), and high-dose MTX (≥12.5 mg/wk). The 2-year persistence of the initial MTX regimen was computed by the Kaplan–Meier method, and a Cox proportional hazard model was developed to examine potential predictors of MTX withdrawal/change of dosage. European League Against Rheumatism remission and good-to-moderate response were evaluated according to baseline MTX regimen and MTX maintenance over time.ResultsA total of 330 patients (163 treated with adalimumab and 167 with etanercept) were included; 141 were prescribed TNFi without MTX and 112 received low-dose and 77 high-dose concomitant MTX. Male sex, younger age, and shorter mean disease duration were predictors of high-dose MTX use. Among MTX users (76.2% parenteral and 23.8% oral), initial MTX dose persisted over time in 79.9% at 1 year and 70.2% at 2 years. Fifty-one patients (27%) underwent MTX dose de-escalation/discontinuation because of intolerance/adverse events. The 2-year EULAR remission rate was higher in the patients receiving and maintaining high-dose MTX than in those receiving low-dose or no MTX (46.2% vs 29.5% and 23.4%, respectively; p=0.009). The same was true for good-to-moderate response rate (71.2% vs 52.6% and 50.4%, respectively; p=0.031).ConclusionIn a real-life setting, about one-third of RA patients treated with TNFis experienced dose reduction/discontinuation of concomitant MTX because of intolerance/adverse events over a 2-year follow-up period. Initial high-dose MTX and its maintenance over time are associated with better 2-year clinical response.

Molecular Insights of Hyaluronic Acid as Potential Source of Polymer-Drug Conjugate in the Target-Mediated Treatment of Cancer

The naturally occurring polysaccharide hyaluronic acid (HA) is a major component of the extracellular matrix and is found over expressed in many cancer cells. Hyaluronic acid is reported to be a potential carrier for drug delivery with the dual advantage of accumulation at the tumor site and receptor-mediated uptake. The use of drugs conjugated with macromolecules was shown to improve the drug pharmacokinetic profile. The various biological potentials such as biodegradability, biocompatibility, non-toxicity, hydrophilicity and non-immunogenicity, together with the availability of various chemical groups that allow the conjugation of drugs, put forward HA as a potential choice for the development of drug conjugates. In this context, the present study is focused to provide, through docking studies, insights on the activity of cancer drugs such as methotrexate, 3′,5′-dichloromethotrexate and ornithine-methotrexate and their activity against the receptor caspase-1, which is a well-established drug target in the treatment of cancer. The docking study envisages that the usage of methotrexate properly conjugated to the natural polysaccharide HA might serve as a potential drug to effectively treat some cancer diseases.

Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease-Related Indicators, and Associations With Cardiometabolic RiskFactors.

Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown-like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non-RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown-like structures was more than 1.5-fold higher in the RA group than in controls (0.58 versus 0.23 crown-like structure/high-power field, respectively; P= 0.001). ATMs were significantly more abundant in early RA and in those with anti-cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown-like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C-reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. ATMs and crown-like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown-like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.

Adding patient-reported outcomes to a multisite registry to quantify quality of life and experiences of disease and treatment for youth with juvenile idiopathic arthritis

BackgroundChildren with Juvenile Idiopathic Arthritis (JIA) often have poor health-related quality of life (HRQOL) despite advances in treatment. Patient-centered research may shed light on how patient experiences of treatment and disease contribute to HRQOL, pinpointing directions for improving care and enhancing outcomes.MethodsParent proxies of youth enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry shared patient-reported outcomes about their child’s HRQOL and experiences of disease and treatment burden (pain interference, morning stiffness, history of medication side effects and methotrexate intolerance). Contributions of these measures to HRQOL were estimated using generalized estimating equations accounting for site and patient demographics.ResultsPatients (N = 180) were 81.1% white non-Hispanic and 76.7% female. Mean age was 11.8 (SD = 3.6) years, mean disease duration was 7.7 years (SD = 3.5). Mean Total Pediatric Quality of Life was 76.7 (SD = 18.2). Mean pain interference score was 50.1 (SD = 11.1). Nearly one-in-five (17.8%) youth experienced >15 min of morning stiffness on a typical day, more than one quarter (26.7%) reported ≥1 serious medication side effect and among 90 methotrexate users, 42.2% met criteria for methotrexate intolerance. Measures of disease and treatment burden were independently negatively associated with HRQOL (all p-values <0.01). Negative associations among measures of treatment burden and HRQOL were attenuated after controlling for disease burden and clinical characteristics but remained significant.ConclusionsFor youth with JIA, HRQOL is multidimensional, reflecting disease as well as treatment factors. Adverse treatment experiences undermine HRQOL even after accounting for disease symptoms and disease activity and should be assessed routinely to improve wellbeing.

Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients

IntroductionRheumatoid arthritis is a systemic inflammatory disease, and classical disease-modifying antirheumatic drugs (cDMARDs) have proven efficacy. It is unknown what impact cDMARDs might have on dementia as an outcome. MethodsIncident diagnoses of rheumatoid arthritis in persons over 18 years from 1995 to 2011 were identified from the UK Clinical Practice Research Datalink. There were 3876 cDMARD users and were propensity score matched to 1938 nonusers, on a wide range of confounders. Impact on dementia was assessed using survival models. ResultscDMARD users were at reduced risk of dementia (hazard ratio: 0.60; 95% confidence interval: 0.42–0.85). The effect was strongest in methotrexate users (hazard ratio: 0.52; 95% confidence interval; 0.34–0.82). DiscussionThe strong effect of cDMARD use on halving of dementia risk requires replication in a trial and may provide an important therapeutic pharmacological treatment.

A national survey of nurse training: Confidence and competence in educating patients commencing methotrexate therapy.

Methotrexate is routinely used to treat active disease in inflammatory arthritis. There have previously been patient safety concerns associated with methotrexate usage in practice. Most patients commencing methotrexate treatment are seen by the rheumatology nurse, to receive education (often referred to as drug counselling) on this agent prior to starting treatment. Yet, there are no recommended criteria regarding education or experience to ensure minimum competence of the rheumatology nurse. The objectives of the present survey were, firstly, to identify the relevant training experience of rheumatology nurses who provide methotrexate education and, secondly, to explore their confidence and competence in undertaking this role. A national electronic survey of rheumatology nurses, identified via the Royal College of Nursing Rheumatology Forum, national meetings and personal contacts, in order to access nurses who counsel patients on methotrexate, was carried out. A total of 104 nurses completed the survey. Reported training was highly variable, ranging from very little to having undertaken MSc courses. Knowledge of the drug was rated as the most important requirement. Confidence was largely very good and was reported to develop with experience, with 80% of participants reporting being confident after 1 year in the role. A small number of participants (four) indicated that they were 'not at all confident'. Aspects of competence and knowledge were assessed using questions on clinical situations; knowledge appeared to be good, with the exception of a question on shingles. Confidence correlated with knowledge (r = 0.21; p = 0.05), amount of training (r = 0.24; p = 0.03) and most strongly with time in the role (r = 0.74; p = 0.00001). The amount of training correlated with confidence but not with knowledge. All participants used written information, often using more than one source, with 87% of participants favouring the Arthritis Research UK information leaflet on methotrexate. There was a wide variety of training for this role. Confidence seemed to come with experience, training and knowledge, and took many months to develop. A training package in this area may be helpful. Reassuringly, confidence and knowledge were related.

Clinical efficacy and quality of life under micronutrients in combination with methotrexate therapy in chronic plaque of psoriatic patients

Abstract Background/objectives Psoriasis is a common dermatologic disorder, with fluctuating response to treatments. We aimed to investigate the efficacy of methotrexate (MTX) plus micronutrient supplement (MM) compare to MTX only on Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) in psoriasis patients in a double-blinded clinical trial study. Materials and methods A total number of 30 psoriasis patients who had lesions up to 20 percent of body skin involvement were divided randomly into two groups. Group A were treated by oral methotrexate and group B were received the MTX plus one tablet of micronutrient supplement daily for 12 weeks. Clinical response (scaling, erythema, involvement and thickness of patient's lesion), PASI score and DLQI index were recorded baseline and after 12 weeks. PASI-50, PASI-75, and PASI-90 evaluated as indicators of clinical improvements. Results PASI 50/75/90 response rates were 100%, 73.3%, 40% in group B and they were 66.6%, 40%, 20% in group A respectively. Both treatments were effective and caused significant improvements in PASI score and DLQI (P Conclusion Daily usage of supplements along with methotrexate is safe and concomitant with the significant reduction of PASI score and improvement of DLQI compared to the usage of MTX alone.

Molecular Insights of Hyaluronic Acid as Potential Source of Polymer-Drug Conjugate in the Target-Mediated Treatment of Cancer

The naturally occurring polysaccharide hyaluronic acid (HA) is a major component of the extracellular matrix and is found over expressed in many cancer cells. Hyaluronic acid is reported to be a potential carrier for drug delivery with the dual advantage of accumulation at the tumor site and receptor-mediated uptake. The use of drugs conjugated with macromolecules was shown to improve the drug pharmacokinetic profile. The various biological potentials such as biodegradability, biocompatibility, non-toxicity, hydrophilicity and non-immunogenicity, together with the availability of various chemical groups that allow the conjugation of drugs, put forward HA as a potential choice for the development of drug conjugates. In this context, the present study is focused to provide, through docking studies, insights on the activity of cancer drugs such as methotrexate, 3′,5′-dichloromethotrexate and ornithine-methotrexate and their activity against the receptor caspase-1, which is a well-established drug target in the treatment of cancer. The docking study envisages that the usage of methotrexate properly conjugated to the natural polysaccharide HA might serve as a potential drug to effectively treat some cancer diseases.

Association Between Medications and Herpes Zoster in Japanese Patients with Rheumatoid Arthritis: A 5-year Prospective Cohort Study.

To investigate the association between medications and herpes zoster (HZ) in patients with rheumatoid arthritis (RA) given biological disease-modifying antirheumatic drugs (bDMARD) or conventional synthetic DMARD in the clinical setting during 5 years using the Registry of Japanese Rheumatoid Arthritis Patients on Biologics for Longterm Safety (REAL) database. We calculated the crude incidence rate (IR) of HZ treated with systemic antiviral medications in 1987 patients from the REAL database. To estimate the association between HZ and medications, a nested case control study was performed with 1:5 case-control pairs matched for age, sex, observation start year, and comorbidity (HZ case group, n = 43; control group, n = 214). We calculated OR and 95% CI of the use of bDMARD, methotrexate (MTX), and corticosteroids for the occurrence of HZ using a conditional logistic regression analysis. The median patient age was 60.0 years, female proportion was 81.5%, and median disease duration was 6.0 years. The crude IR (95% CI) of HZ was 6.66 (4.92-8.83)/1000 person-years. The OR (95% CI) of medication use were 2.28 (1.09-4.76) for tumor necrosis factor inhibitor (TNFi) and 1.13 (1.03-1.23) for oral corticosteroids dosage (per 1 mg prednisolone increment), both of which were significantly elevated. The OR of non-TNFi and MTX usage were not elevated. TNFi use and higher corticosteroids dosage were significantly associated with HZ in Japanese patients with RA in the clinical setting.

Folic Acid Supplementation Is Suboptimal in a National Cohort of Older Veterans Receiving Low Dose Oral Methotrexate.

ObjectivesCo-prescription of folic acid in patients receiving low dose oral methotrexate is recommended because it reduces adverse events and prolongs the use of methotrexate (MTX). However, little is known about how often new users of methotrexate are co-prescribed folic acid, and what factors are associated with its use. We aimed to determine the prevalence, predictors of, and persistence of folic acid use in a population-based cohort of MTX users with rheumatic diseases.MethodsUsing a national, administrative database of patients seen through the Veterans Health Administration (VHA) that included pharmacy and laboratory data, we performed an observational cohort study of veterans over 65 years old who were new users of MTX. We used log-binomial regression to identify independent predictors of folic acid use and Kaplan Meyer survival analysis to examine persistence of folic acid over time.ResultsWe studied 2467 incident users of MTX. 27% of patients were not prescribed folic acid through the VHA pharmacy within 30 days of MTX initiation. Patients who did not see a rheumatologist were 23% less likely to receive folic acid compared to patients who did have a rheumatologist visit during the baseline period (RR (95% CI) 0.77 (0.72, 0.82). These results remained unchanged even after adjusting for demographic, clinical, and other factors (adjusted RR (95% CI) 0.78 (0.74, 0.85)). After 20 months, only 50% of patients continued to receive folic acid.ConclusionsIn a nationwide VHA cohort of new users of oral MTX, many patients did not receive folic acid or discontinued it over time. Rheumatologists were more likely to prescribe folic acid than other providers. These data highlight the need to improve patient safety for users of methotrexate by standardizing workflows for folic acid supplementation.

Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate

Psoriasis is associated with increased risk for cardiovascular disease. To compare major cardiovascular event risk in psoriasis patients receiving methotrexate or tumor necrosis factor-α inhibitor (TNFi) and to assess TNFi treatment duration impact on major cardiovascular event risk. Adult psoriasis patients with ≥2 TNFi or methotrexate prescriptions in the Truven MarketScan Databases (Q1 2000-Q3 2011) were classified as TNFi or methotrexate users. The index date for each of these drugs was the TNFi initiation date or a randomly selected methotrexate dispensing date, respectively. Cardiovascular event risks and cumulative TNFi effect were analyzed by using multivariate Cox proportional-hazards models. By 12months, TNFi users (N=9148) had fewer cardiovascular events than methotrexate users (N=8581) (Kaplan-Meier rates: 1.45% vs 4.09%: P<.01). TNFi users had overall lower cardiovascular event hazards than methotrexate users (hazard ratio=0.55; P<.01). Over 24months' median follow-up, every 6months of cumulative exposure to TNFis were associated with an 11% cardiovascular event risk reduction (P=.02). Lack of clinical assessment measures. Psoriasis patients receiving TNFis had a lower major cardiovascular event risk compared to those receiving methotrexate. Cumulative exposure to TNFis was associated with a reduced risk for major cardiovascular events.

Comparative Effectiveness of Common Immunomodulator Agents over 5 Year Clinical Outcomes in Crohnʼs Disease Patients

Introduction: Studies comparing the therapeutic impact of immunomodulators in Crohn's disease (CD) are limited. Lémann Index (LI) quantifies bowel damage in CD and change in LI or Delta Lémann Index (DLI) may be used to track damage trajectory. We compared the clinical course and damage trajectories of CD patients on different immunomodulators.Table 1: Comparison of Crohn's disease related characteristics, healthcare utilization and bowel damage trajectories in subgroups stratified based on the use of immunomodulator agentsMethods: Using a registry maintained at a tertiary center, CD patients with yearly clinical encounters and on treatment with any single immunomodulator for ≥3 years(y) during a 5y follow-up, were included. Analysis was limited to the commonly utilized agents at our center: azathioprine (AZA), 6-mercaptopurine (6MP) and methotrexate (MTX). LI was calculated from the first (LI1) and last (LI2) clinical encounters and DLI was calculated as LI2-LI1. Comparative analysis was done amongst groups created based on immunomodulator used. Results: A total of 145 CD patients formed the study cohort [median age 44y (IQR: 33-56); 53.8% female; median disease duration 9y (IQR: 6-19), overall surgical exposure 65.5%]. AZA, 6MP and MTX were used by 54.5%, 26.2% and 19.3% of the cohort respectively. In the MTX group, 12 (42.9%) patients had prior AZA/6MP exposure and were switched to MTX due to ineffectiveness (n=8/12) or adverse reactions (n=4/12). Also, 19 (67.9%) patients had prior anti-TNF agent exposure and MTX was used instead or added on due to ineffectiveness (n=10/19) or adverse reactions (n=6/19). The 3 groups showed no significant differences in age, age at onset, disease duration, location or behavior. The MTX group had significantly higher CD related surgical exposure, more frequent biochemical markers' elevation, higher 5y healthcare utilization and was more often on steroids and anti-TNF agents. Trajectory of deterioration (DLI>0) was more frequent in MTX group. On univariate analysis, deterioration showed significant positive correlation with use of MTX (r=0.199; p=0.017) and negative correlation with use of 6MP (r=-0.191; p=0.021); however, no significant association was noted on multivariate analysis. Conclusion: CD patients treated with MTX have worse 5y clinical outcomes, compared to AZA and 6MP users. This could reflect a patient subset with more refractory disease for which we usually reserve MTX, or a group that loses access to more effective therapies due to intolerance. Further studies to better characterize outcomes in MTX users with intention to limit less effective therapies are warranted.

Association Between Breast Cancer Recurrence and Immunosuppression in Rheumatoid Arthritis and Inflammatory Bowel Disease: A Cohort Study.

Breast cancer recurrence may be promoted by immunosuppression due to decreased immune surveillance. The aim of this study was to examine the rates of breast cancer recurrence in patients with immune-mediated disease and treated breast cancer who received therapy with methotrexate, thiopurines, or anti-tumor necrosis factor (anti-TNF). Three retrospective cohort studies within Medicare (2000-2012) included women with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) who underwent surgery for primary breast cancer. Recurrent or second primary breast cancers occurring more than 365 days after the initial surgery were identified. Separate Cox regression models were used to examine the risk of cancer recurrence in patients treated with methotrexate, thiopurines, or anti-TNF agents after surgery, each compared with no use. Analyses were matched for type of breast surgery and receipt and type of adjuvant therapy. Across all medication groups, 107 women experienced breast cancer recurrence during 5,196 person-years. The incidence rates were 20.3 and 19.6 per 1,000 person-years in methotrexate users and nonusers, respectively, 32.3 and 17.6 in thiopurine users and nonusers, respectively, and 22.3 and 19.5 in anti-TNF users and nonusers, respectively. There was no significantly increased risk of breast cancer recurrence with use of methotrexate (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.67-1.69), anti-TNF therapy (HR 1.13, 95% CI 0.65-1.97), or thiopurines (HR 2.10, 95% CI 0.62-7.14). The risk of breast cancer recurrence in patients who received methotrexate, thiopurine, or anti-TNF therapy was not statistically significantly increased, although we cannot rule out a 2-fold or greater increased risk in those treated with thiopurines. These data provide reassurance to clinicians choosing to start methotrexate or anti-TNF therapy in RA or IBD patients with treated breast cancer.

The risk of hospitalized infection following initiation of biologic agents versus methotrexate in the treatment of juvenile idiopathic arthritis.

BackgroundIn the present study, we compared the incidence of hospitalized infection among children with juvenile idiopathic arthritis (JIA) following initiation of treatment with biologic agents versus methotrexate (MTX).MethodsWe used national Medicaid claims data from 2000 through 2010 to create cohorts of children with JIA who were new users of tumor necrosis factor inhibitors (TNFi), anakinra, and MTX (without concurrent biologic agent use) as defined by a 6-month baseline period of nonuse. Because most anakinra users have systemic juvenile idiopathic arthritis (SJIA), we used claims to identify MTX users who likely had SJIA. Among TNFi users, concurrent MTX use was a time-varying covariate. The study outcome was a primary hospital discharge diagnosis of infection. We calculated adjusted hazard ratios (aHRs) to compare infection rates between biologic agents and MTX.ResultsWe identified 3075 new MTX users (160 with SJIA), 2713 new TNFi users, and 247 new anakinra users. There was no increased risk of infection associated with TNFi monotherapy versus MTX (aHR 1.19, 95 % CI 0.72–1.94) or with TNFi + MTX combination therapy versus MTX (aHR 1.23, 95 % CI 0.69–2.17). Baseline high-dose oral glucocorticoid use (≥10 mg/day of prednisone) was associated with infection (aHR 2.03 [95 % CI 1.21–3.39] versus no oral glucocorticoid). Anakinra was associated with infection versus MTX (aHR 3.53 95 % CI 1.83–6.82), but less so compared with MTX users with SJIA (aHR 2.69, 95 % CI 0.82–8.82).ConclusionsNeither TNFi monotherapy nor TNFi + MTX combination therapy was significantly associated with hospitalized infection compared with MTX. Anakinra was significantly associated with infection, but there was likely residual confounding by disease phenotype.

Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis C.

A few studies have shown that methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients, although the risk is low compared to psoriatics. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis C (CHC)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 450 incident cases of RA among CHC patients (255 MTX users and 195 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 5 years since the diagnosis of CHC, a total of 55 (12%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHC patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among the 43 MTX users with a cumulative dose ≧3 grams after 108 months of treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHC. However, these results should be interpreted with caution due to potential bias in the cohort.