Methotrexate Treatment In Patients Research Articles

Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis

BackgroundSarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking.ObjectiveIn this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy.MethodsProtein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment).ResultsSerum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032).ConclusionThis study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis.

Pulse azathioprine (AZA) and low dose methotrexate (MTX) versus standard dose MTX in treatment of patients with moderate to severe psoriasis, a randomized controlled trial.

Psoriasis is a common chronic, immune-mediated inflammatory skin disease. Despite the availability of several systemic therapeutic agents, treatment of psoriasis remains a challenge because of the associated adverse effects and/or the financial burden of these medications, given the chronicity of the disease. We aimed to compare the efficacy and safety of combined pulse azathioprine (AZA) and low dose methotrexate versus conventional dose of methotrexate (MTX) in patients with chronic plaque psoriasis. In this randomized controlled trial, 67 patients with moderate to severe plaque psoriasis were randomized into 2 groups, receiving either combined pulse AZA (300 mg weekly dose) and low dose MTX (10 mg weekly) or conventional dose MTX (0.3 mg/kg/week) for 16 weeks. Patients were assessed for treatment response using PASI score and for the development of any adverse effects at weeks 12 and 16 and for a further 3 months after stoppage of treatment. A statistically significant higher proportion of the patients receiving combined pulse AZA and low dose MTX achieved PASI 90 and PASI 100 at week 12 and PASI 100 at week 16, compared to those receiving conventional dose of MTX monotherapy. No serious adverse events were reported during the entire study period in the two groups. Combination therapy using pulse AZA and low dose MTX can be an efficacious treatment for moderate to severe plaque psoriasis with a relatively good safety profile.

ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis.

Methotrexate (MTX) is one of the most extensively used drugs in the treatment of moderate-to-severe psoriasis (PS). However, it frequently must be suspended owing to the toxicity in certain patients. To evaluate the influence of ABCC1, ABCG2, and FOXP3 in the development of MTX toxicity in PS. Retrospective cohort study with 101 patients. Five single-nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction with TaqMan probes. Patients carrying ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.04; 95% CI = 1.48-46.78; p = 0.015); FOXP3 rs376154-GT and GG genotypes (GT vs. TT/GG: OR = 3.86; 95% CI = 1.17-13.92; p = 0.031) and ABCG2 rs13120400-T allele (T vs. CC: OR = 8.33; 95% CI = 1.24-164.79; p = 0.059) showed a higher risk of developing more than one adverse effect. The toxicity analysis by subtypes showed that the ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.10; 95% CI = 1.69-46.63; p = 0.011) and FOXP3 rs376154-GT genotype (OR = 4.11; 95% CI = 1.22-15.30; p = 0.027) were associated with the appearance of asthenia. No association of the other ABCC1 polymorphisms (rs35592 and rs246240) with MTX toxicity was found. ABCC1, ABCG2, and FOXP3 polymorphisms can be considered to be risk biomarkers of toxicities in PS patients treated with MTX.

Can Methotrexate Be Employed as Monotherapy for Bullous Pemphigoid? Analysis of Efficiency and Tolerance of Methotrexate Treatment in Patients with Bullous Pemphigoid.

The European Academy of Dermatology and Venerology (EADV) consensus states that the treatment of choice for bullous pemphigoid is systemic glucocorticosteroid therapy. Bearing in mind that long-term steroid therapy is associated with numerous side effects, an effective and safer treatment regimen for these patients is still being sought. A retrospective analysis was performed of the medical reports of patients with diagnosed bullous pemphigoid. The study included 40 patients with moderate or severe disease, and who had continued ambulatory treatment for at least six months. The patients were divided into two groups: one treated with methotrexate in monotherapy, or with combined methotrexate and systemic steroid therapy. A slightly better survival rate was noted in the methotrexate group. No significant differences were observed between the groups in time to achieve clinical remission. The combination therapy group demonstrated more frequent disease recurrence and exacerbations during treatment, and a higher mortality rate. None of the patients in either group presented with severe side effects related to methotrexate treatment. The treatment of bullous pemphigoid with methotrexate in monotherapy is an effective and safe therapeutic method for elderly patients.

P16.01.A Factors predicting cognitive impairment after intrathecal methotrexate treatment in patients with non-small cell lung cancer and leptomeningeal disease

Abstract Background Leptomeningeal disease (LD) is a devastating cancer-related neurological complication. LD accounts for 4-15% of patients with non-small cell lung cancer (NSCLC). In this population, the median overall survival (OS) with intrathecal (IT) methotrexate (MTX) plus systemic therapy (ST) is 4-6 months (m). Until now, disease and treatment-related cognitive impairment (CI) has been poorly studied in this group. Material and Methods Patients with NSCLC and LD treated with IT MTX in our institution between 2010 and 2021 were retrospectively studied. LD was diagnosed based on positive cerebrospinal fluid cytology or radiological findings in the brain/spinal MRI plus suitable clinical signs/symptoms. IT MTX (12mg twice weekly for 4 weeks, then 12mg weekly for 4 weeks) was given in combination with ST. Patients’ clinical characteristics and patient-reported CI were assessed at baseline and at 3-months post IT MTX. A Kaplan-Meier survival analysis was performed. Primary endpoint: predictive factors of CI at 3m post IT MTX. Secondary endpoint: prognostic factors. Results Out of 55 patients included, 51% were male and median age at LD diagnosis was 59 years old (range 38-78). Most patients had an ECOG PS≤1 (76.4%) and adenocarcinoma histology (83.6%). 47% of patients harbored EGFR mutation. In 23.6% of patients LD was diagnosed synchronously with lung tumor and for patients without LD at tumor diagnosis, the median time to LD development was 8m (range 0-73). Clinical features at LD diagnosis were 43.7% infratentorial symptoms, 29% CI, 20% multiple symptoms and 7% asymptomatic. At LD diagnosis, 53% of patients had synchronous brain metastases (BM) and in 38% the systemic disease was not controlled. 85.5% of patients received ST concurrently with IT MTX (N=22 chemotherapy, N=22 TKIs and N=3 immunotherapy). 14.5% of patients did not receive ST. Median OS from IT was 5m (95% CI 1.3-8.6). ECOG PS and ST administered concurrently with IT MTX was associated with longer OS (p<0.05). 23.6% of patients developed CI at 3m post IT therapy. Median OS for patients without and with CI post IT therapy was 6m (95% CI 0.7-11.3) vs 4m (95% CI 0.5-75) respectively (p=0.15). Patients with leukoencephalopathy at baseline (score≥2in the periventricular Fazekas’ score) (p=0.033), women (p<0.01) and those ≥60 years (p=0.04) were more likely to present CI 3m post IT MTX. The presence of cardiovascular risk factors, previous brain radiotherapy and concurrent BM was not statistically associated with CI. Conclusion In this cohort, 24% of patients with NSCLC and LD treated with IT MTX will develop CI 3m post treatment. Baseline leukoencephalopathy, female gender, elder than 60 years old were more likely to exhibit CI after IT MTX. A better characterization of these patients is warranted to develop new treatment strategies to prevent/reduce CI.

Clinical predictors of response to methotrexate in patients with rheumatoid arthritis: a machine learning approach using clinical trial data

BackgroundMethotrexate is the preferred initial disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA). However, clinically useful tools for individualized prediction of response to methotrexate treatment in patients with RA are lacking. We aimed to identify clinical predictors of response to methotrexate in patients with rheumatoid arthritis (RA) using machine learning methods.MethodsRandomized clinical trials (RCT) of patients with RA who were DMARD-naïve and randomized to placebo plus methotrexate were identified and accessed through the Clinical Study Data Request Consortium and Vivli Center for Global Clinical Research Data. Studies with available Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) at baseline and 12 and 24 weeks were included. Latent class modeling of methotrexate response was performed. The least absolute shrinkage and selection operator (LASSO) and random forests methods were used to identify predictors of response.ResultsA total of 775 patients from 4 RCTs were included (mean age 50 years, 80% female). Two distinct classes of patients were identified based on DAS28-ESR change over 24 weeks: “good responders” and “poor responders.” Baseline DAS28-ESR, anti-citrullinated protein antibody (ACPA), and Health Assessment Questionnaire (HAQ) score were the top predictors of good response using LASSO (area under the curve [AUC] 0.79) and random forests (AUC 0.68) in the external validation set. DAS28-ESR ≤ 7.4, ACPA positive, and HAQ ≤ 2 provided the highest likelihood of response. Among patients with 12-week DAS28-ESR > 3.2, ≥ 1 point improvement in DAS28-ESR baseline-to-12-week was predictive of achieving DAS28-ESR ≤ 3.2 at 24 weeks.ConclusionsWe have developed and externally validated a prediction model for response to methotrexate within 24 weeks in DMARD-naïve patients with RA, providing variably weighted clinical features and defined cutoffs for clinical decision-making.

Genetic Markers of Therapeutic Efficacy of Methotrexate in Patients with Psoriasis.

We studied the effect of C677T and A1298C polymorphisms of the MTHFR gene and 2R/3R polymorphisms of the TYMS gene on the sensitivity to methotrexate in patients with psoriasis (n=139). It was shown that genotype 3R/3R TYMS (OR 8.86, 95%CI 2.00-39.22) and complex genotypes MTHFR1298:A;TYMS:3R (OR 8.20, 95%CI 2.36-28.48) and MTHFR677:C;TYMS:3R (OR 5.40, 95%CI 1.95-14.94) were associated with sensitivity to methotrexate, while genotype 2R/2R TYMS (OR 8.20, 95%CI 2.36-28.48) and complex genotypes MTHFR1298:C;MTHFR677:T;TYMS:2R (OR 0.18, 95%CI 0.06-0.56) and MTHFR1298:C;MTHFR677:T (OR 0.23, 95%CI 0.09-0.59) were associated with resistance to methotrexate. The results can be used for preventive assessment of the effectiveness of methotrexate treatment in patients with psoriasis.

Comparative study between Corticosteroid and Methotrexate treatment for patients with orbital pseudo tumor

Comparative study between Corticosteroid and Methotrexate treatment for patients with orbital pseudo tumor

Effectiveness and safety of levilimab in combination with methotrexate in treatment of patients with active rheumatoid arthritis resistant to methotrexate monotherapy (double-blinded randomized placebo controlled phase III clinical study SOLAR)

Levilimab is anti-interleukin-6 receptor (IL6R) monoclonal antibody. The article presents data obtained during 24 weeks of the SOLAR phase III study.Objective: to confirm efficacy and safety of levilimab in combination with methotrexate (MTX) in patients with methotrexate resistant active rheumatoid arthritis (RA).Patients and methods. 154 adult patients, aged ≥18 years with the diagnosis of RA (ACR/EULAR 2010) and confirmed disease activity at screening despite treatment with MTX for at least 12 weeks (in a stable dose 15-25 mg/week). Patients were randomized 2:1 in levilimab (162 mg once a week, subcutaneously) + MTX (n=102) or placebo + MTX (n=52) group.The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy endpoints: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved low disease activity (LDA) of RA (DAS28-CRP <3.2) at week 24. Safety was assessed through monitoring of adverse events (AEs).Results and discussion. Seventy (68.6%) subjects who received levilimab and 20 (38.5%) who received placebo achieved ACR20 response at week 12. Fifty three (52%) subjects who received levilimab and 3 (5,8%) subjects who received placebo achieved LDA at week 24. The most common adverse events (reported in ≥5% of subjects) in levilimab and placebo arms, respectively were (by decreasing frequency): blood c holesterol increase (24% vs 12%), alanine aminotransferase elevation (11% vs 8%), lymphocyte count decrease (9% vs 8%), blood total bilirubin increase (11% vs 0%), blood triglycerides increase (10% vs 2%), aspartate aminotransferase elevation (7% vs 4%), positive interferon-gamma release assay (IGRA) with M.tuberculosis antigen blood test (5% vs 6%), absolute neutrophil count decrease (8% vs 0%). No deaths were occurred.Conclusion. The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. Levilimab showed favorable safety profile and low immunogenicity. No new important safety risks were detected.

Does methotrexate influence the efficacy of vaccination against SARS-CoV-2?

Die Frage, ob eine laufende MTX(Methotrexat)-Therapie tatsächlich die protektive Immunantwort nach SARS-CoV-2-Impfung in relevanter Form abschwächt, lässt sich anhand der vorliegenden Daten definitiv nicht beantworten. In Kenntnis der Tatsache, dass ein kurzes z. B. 1‑ oder 2‑maliges Pausieren der wöchentlichen MTX-Gabe bei Patienten in stabiler Krankheitssituation mit einem vergleichsweise geringen Risiko der Auslösung eines Schubes der Grundkrankheit verbunden ist, kann eine solche kurze Unterbrechung der Therapie nach individueller Entscheidung zwischen Patient*in und behandelnder/m Rheumatolog*in durchaus erwogen werden. Zwingend notwendig erscheint sie aber nicht – zumal diese Pause bei den meisten Impfstoffen 2‑mal innerhalb relativ kurzer Zeit erfolgen müsste. Keinesfalls aber sollte eine längere Therapiepause gemacht werden – die Auslösung eines Schubes der Grundkrankheit wäre eine mögliche kritische Folge. Für eine ausführlichere Einschätzung der Datenlage und der Konsequenzen daraus (auch in Bezug auf weitere DMARD [„disease-modifying anti-rheumatic drugs“]) wird auf die demnächst erscheinenden aktualisierten Handlungsempfehlungen der DGRh (Deutsche Gesellschaft für Rheumatologie e. V.) für die Betreuung von Patienten mit entzündlich rheumatischen Erkrankungen im Rahmen der SARS-CoV-2/COVID-19-Pandemie verwiesen.

ЕФЕКТИВНІСТЬ ЗАСТОСУВАННЯ МЕТОТРЕКСАТУ У ЛІКУВАННІ РЕЦИДИВІВ САРКОЇДОЗУ ЛЕГЕНЬ

EFFECTIVENESS OF METHOTREXATE IN MANAGEMENT OF PULMONARY SARCOIDOSIS RELAPSES N. A. Vlasova Abstract Relapses are one of most urgent problems of treatment in pulmonary sarcoidosis patients. There have been demonstrated the correlation between the rate of pulmonary sarcoidosis relapses and previous longterm glucocorticosteroid (GCS) therapy. This makes a feasibility of GCS administration in patients with relapsing disease doubtful. Literature data and author’s clinical experience considering lower incidence of sarcoidosis relapses after the use of immunosuppressive drugs such as methotrexate (MTX) were the rationale for this study. Aim: to study the efficacy of MTX in treatment of patients with the relapses of pulmonary sarcoidosis. Material and methods. We examined 12 patients (5 males and 7 females, 36-54 years of age) with relapses of pulmonary sarcoidosis, revealed within 12 months after successful completion of main course of methylprednisolone (MP) therapy (clinical cure). MTX was prescribed in dose of 15 mg/week under monthly control of white blood cells and platelets count and alanine aminotransferase (ALT) serum level. Therapy has been stopped after the complete cure, confirmed by lung computed tomography (CT). The primary endpoint was the long-term outcomes of MTX use – the rate of repeated relapses during 12 months follow-up period following MTX discontinuation. The control group was comprised of 33 patients (males 14, females 19, 30-58 years of age) with relapses of pulmonary sarcoidosis after completion of GCS therapy, treated with MP at initial dose of 24 mg/day. Therapy has been stopped after the complete cure, confirmed by lung CT. The long-term outcomes were assessed at 6 and 12 months of follow-up. Additionally, incidence of adverse reactions was compared between groups. Exact Fisher’s test was used to determine the differences between studied variables. Results. No significant differences were found in rate of adverse reactions between study groups (16,7 % in МТХ vs 21,2 % in MP group). At the same time the rate of repeated relapses was lower in MTX than in MP group (25 % vs 57,6 %, respectively, p=0,01993). Conclusion. Use of MTX 15 mg/week in patients with relapses of pulmonary sarcoidosis was associated with less frequent repeated relapses in comparison with conventional use of MP at starting dose 24 mg/day. Key words: pulmonary sarcoidosis, relapse, methotrexate, methylprednisolone.

Six-month flare risk after discontinuing long-term methotrexate treatment in patients having rheumatoid arthritis with low disease activity.

We investigated the disease flare rate in patients with rheumatoid arthritis (RA) who achieved low disease activity following long-term methotrexate (MTX) treatment and the factors related to flare. This retrospective longitudinal cohort study included patients with RA and low disease activity who were exposed to MTX for >10years. Disease flare was defined as an increase in Disease Activity Score of 28 joints (DAS28) of >1.2 within 6months of discontinuation of MTX. Logistic regression analysis was performed to identify the factors associated with flare. In total, 97 patients with RA were included in the study. The mean baseline DAS28 was 1.96±0.56. The median cumulative MTX dose was 11.7g; the median duration of exposure to MTX was 19years. Following MTX discontinuation, flare occurred in 43 (44.3%) patients; the median time to flare was 99 (28-168) days. According to univariate logistic regression analysis, C-reactive protein, erythrocyte sedimentation rate (ESR) at discontinuation, the average ESR in the 6months before discontinuation of MTX, a weekly dose of MTX before discontinuation, and use of other conventional synthetic disease-modifying antirheumatic drugs were associated with a higher risk of disease flare. In multivariable analysis, a weekly dose of MTX before discontinuation (odds ratio 1.014; 95% CI 1.014-1.342; P=.031) was significantly associated with flare risk. Among patients with RA who achieved low disease activity with long-term treatment with MTX, more than half remained flare free after MTX discontinuation. A higher MTX dose before discontinuation was associated with a high flare risk.

Regulatory T cells in patients with early untreated rheumatoid arthritis: Phenotypic changes in the course of methotrexate treatment

Rheumatoid arthritis (RA) is frequent systemic autoimmune disease characterized by excessive activation of collagen-specific T helper cells, and elevated level of autoantibodies in the serum. Development of RA is associated with defect in compartment of regulatory CD4+Foxp3+ T cells (Treg), but data concerning suppressive potential of Treg population in RA patients are contradictory and depend on the stage of disease. In this study we aimed to characterize abundance and phenotypic markers of CD4+Foxp3+ Treg in peripheral blood of healthy donors compared to untreated early RA patients to find potential correlations with the disease activity, antibody level, and absolute numbers and proportion of different subpopulations of T cells. Moreover, we assessed the influence of methotrexate (MT) treatment on percentage and absolute numbers of CD4+Foxp3+ Treg from the peripheral blood of untreated early RA patients. We demonstrate that increase and phenotypic changes in Treg population correlate well with response to MT. Analysis of the cohorts of matched RA patients (n = 45) and healthy controls (n = 20) revealed that patients with untreated early RA demonstrate substantial decrease in blood Treg percentage and absolute number, as well as low level of activated Treg surface markers in comparison to healthy control. The defect in Treg compartment negatively correlates with both RA activity and antibody level. MT treatment of patients with early untreated RA increases both proportion and absolute number of Treg with high level of activation markers, suggesting an increase of their functional capacity. Here we speculate the role of Tregs as specific cellular marker of successful RA treatment.

Methotrexate treatment for patients with psoriasis and risk of cutaneous melanoma: a nested case-control study.

Cutaneous malignant melanoma (CMM) is a highly immunogenic tumour. Patients with an impaired immune system have an enhanced risk for CMM and a worse prognosis. Methotrexate (MTX) is an anti-inflammatory and immunosuppressive drug frequently used to treat patients with psoriasis. An association between MTX and risk of CMM has previously been demonstrated in patients with rheumatoid arthritis. To investigate whether MTX increases the risk of CMM among patients with psoriasis. A nested case-control investigation from a Swedish cohort of patients with psoriasis was conducted. Data were obtained from available Swedish registers and included 395 patients with psoriasis who had previously been cancer-free and had a first CMM in the time period from 1 January 2010 to 31 December 2016. A total of 10 randomly selected cancer-free patients with psoriasis were matched per case with respect to age (same birth year) and sex. The accumulated MTX doses in both groups were obtained. Crude odds ratios (ORs) for the proportion of MTX in the respective group were calculated using conditional logistic regression analyses. Of 395 patients with psoriasis who had CMM, 97 (25%) had filled a prescription of MTX; of 3950 controls, the corresponding number was 954 (24%). In a conditional logistic regression analysis, no association between MTX exposure (ever use) and risk for CMM was observed (OR 1·0, 95% confidence interval 0·8-1·3). Moreover, no indication of a dose-response association was observed. In this Swedish nested case-control study, the use of MTX was not associated with an enhanced risk for CMM. These findings are reassuring for dermatologists in everyday clinical practice. What is already known about this topic? Methotrexate (MTX) treatment has been linked to an increased risk for cutaneous malignant melanoma (CMM) in an Australian cohort of patients with rheumatoid arthritis. In a previous retrospective Swedish cohort investigation, patients who had exclusively been prescribed MTX by a dermatologist did not have an enhanced risk for CMM compared with MTX-unexposed individuals. Nevertheless, this cohort did not specifically include patients with psoriasis. What does this study add? This Swedish nested case-control investigation included 395 previously cancer-free patients with psoriasis who had CMM (cases) and 3950 matched cancer-free patients with psoriasis (controls). No association between MTX exposure and risk for CMM in patients with psoriasis was observed. The results are reassuring for dermatologists using MTX to treat patients with psoriasis. Linked Comment: Haugaard and Egeberg. Br J Dermatol 2020; 183:608-609.

Conservative management of interstitial pregnancies: experience of a single centre

The aim of this study was to compare the effect of local intracavitary methotrexate (MTX) injection and laparoscopic (L/S) cornuostomy in the treatment of interstitial pregnancy (IP) in terms of clinical and reproductive outcome. The data of patients with IP (n:10) who were treated between September 2011 and December 2016 with either an intra-amniotic MTX injection (n:7) or L/S cornuostomy (n:3) were retrospectively evaluated. All cases (7/7) in the local injection group and two (2/3) in the L/S group were successfully treated with the initial treatment. One case (1/3, 33%) in L/S group needed systemic MTX due to an elevated β-hCG. No serious complication or secondary surgical intervention was observed in the study group. Five (71.4%) women in MTX group and two (66%) women in the L/S group had pregnancy after index case (p > .05). Post-treatment (hysterosalpingography) HSG results revealed that tubal patency was significantly higher in the MTX group (7/7 (100%) vs. 0/3 (0%) p < .05). Conservative treatment of IP with both methods was generally successful with regard to maternal morbidity and reproductive function. However, local MTX was superior for tubal patency compared to L/S cornuostomy. Since this is a retrospective study including a small study population, our results should be confirmed with larger prospective studies.Impact StatementWhat is already known on this subject? Earlier diagnosis of an interstitial pregnancy (IP) enables clinicians to pursue more conservative treatment modalities that can prevent morbidity (severe bleeding, rupture and massive transfusion, etc.) and loss of fertility. MTX treatment and conservative laparoscopic surgical procedures are gaining importance. High serum β-hCG levels and positive foetal cardiac activity are known as unfavourable pre-treatment prognostic predictors for systemic MTX treatment in patients with an ectopic pregnancy. Local MTX treatment is widely used for caeserean scar pregnancies or cervical pregnancies. L/S cornuostomy is an attractive alternative to L/S cornual resection, because it preserves the normal uterine myometrium.What the results of this study add? In the present study, we showed that the local MTX and laparoscopic cornuostomy were successful methods in IP patients and did not impair the fertility potential of the patients. We also demonstrated that local MTX application is superior to L/S cornuostomy in terms of the post-treatment tubal patency and this fact should be kept in mind when tailoring the treatment in patients desiring pregnancy.What the implications are of these findings for clinical practice and/or further research? The value of local MTX injection in cases with IP and high β-hCG levels should be further clarified.

Risk factors for abnormal hepatic enzyme elevation by methotrexate treatment in patients with rheumatoid arthritis: A hospital based-cohort study

Objectives: Methotrexate (MTX) is used as first-line treatment of rheumatoid arthritis (RA) worldwide. Large interindividual differences in MTX effectiveness and safety occur, and the most frequent adverse reaction is hepatotoxicity, although the main cause remains unknown. We investigated factors associated with MTX-induced hepatic enzyme elevation in a hospital-based cohort study.Methods: Study participants were 114 Japanese adult RA outpatients prescribed MTX. Sixteen types of single-nucleotide polymorphisms were investigated using real-time PCR. Patient characteristics were collected from the electronic medical records. The onset of MTX-induced abnormal hepatic enzyme elevation was defined according to deviation from normal liver enzyme reference values during treatment. The observation period was 1 year after beginning MTX. Associations between MTX-induced hepatic enzyme elevation and patient characteristics were evaluated using the multivariate logistic regression model.Results: Thirty-two patients experienced MTX-induced abnormal hepatic enzyme elevation. In multivariate analysis, MTX dosage, estimated glomerular filtration rate (eGFR), and genetic polymorphisms of ABCB1 3435C>T and ATIC 347C>G were associated with abnormal hepatic enzyme elevation.Conclusions: MTX-induced abnormal hepatic enzyme elevation in Japanese RA patients was associated with dosage and eGFR as nongenetic factors, and with ABCB1 3435C>T and ATIC 347C>G as genetic factors in this hospital-based cohort study.

The Temporal Relationship between Arterial Stiffening and Blood Pressure Is Modified by Methotrexate Treatment in Patients with Rheumatoid Arthritis.

Background: The temporal relationship between arterial stiffness and blood pressure (BP) may vary depending on age and other clinical and demographic factors. Since both BP and arterial stiffness are also affected by inflammatory processes, we examined the temporal arterial stiffness-BP relationship in patients with rheumatoid arthritis (RA) treated with either methotrexate (MTX), an anti-rheumatic agent shown to reduce cardiovascular risk in meta-analyses, or other disease-modifying anti-rheumatic drugs (DMARDs).Methods: Measurements of clinic and 24-h peripheral and central systolic and diastolic BP (SBP and DBP), and pulse wave velocity (PWV) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, n = 41, age 61 ± 14 years, 73% females) or other DMARDs (non-MTX group, n = 18, age 65 ± 13 years, 89% females). Measurements were performed at baseline and after 8 months. The temporal relationships were examined using cross-lagged path analysis with models that included age, sex, body mass index, prednisolone, and folic acid use and 28-joint disease activity score.Results: There were significant differences in the temporal arterial stiffness-BP relationships between those in the MTX and DMARD groups. A higher PWV at baseline caused a significant increase in 6 out of 8 different measures of SBP at 8 months amongst those treated with DMARDs (standardized β, range = 0.54–0.66, p < 0.003 for each) and 3 out of 8 different measures of DBP (standardized β, range = 0.52–0.61, p < 0.003 for each) but was not associated with either SBP or DBP at 8 months amongst those treated with MTX. The difference in the effect of baseline PWV on 8-month BP between the 2 groups was also significant (p < 0.003) for 4 measures including clinic peripheral SBP (β = 7.0, 95% CI = 2.8–11.1 mmHg per 1 m/s higher baseline PWV; p < 0.001).Conclusions: Higher arterial stiffness preceded increases in BP in subjects with RA treated with DMARDs, but these effects did not occur amongst those treated with MTX. The different effects were seen mostly in measures of SBP but were also present in some measures of DBP. Our findings suggest MTX may confer a protective effect against stiffness mediated increases in BP in patients with RA.

Methotrexate treatment in patients with a history of cutaneous melanoma and the risk of a consecutive primary melanoma: A national retrospective registry-based cohort study

Methotrexate treatment in patients with a history of cutaneous melanoma and the risk of a consecutive primary melanoma: A national retrospective registry-based cohort study

Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial

ObjectivesTo investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone.MethodsMTX-naïve patients with...

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris

Background: Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls.Methods: Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls.Results: The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2–27.7) before the treatment whereas; 3.05 (1–23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p < 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before–after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05).Conclusions: These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.