Use Of Methotrexate In Patients Research Articles

ВЛИЯНИЕ ПРИМЕНЕНИЯ МЕТОТРЕКСАТА НА СОСТОЯНИЕ МИЕЛОПОЭЗА И ТРОМБОЦИТОПОЭЗА У ДЕТЕЙ С ИДИОПАТИЧЕСКИМ АРТРИТОМ

Methotrexate is the mainstay drug in the treatment of juvenile idiopathic arthritis (JIA). The effect of methotrexate on the hematopoietic system manifests itself in the form of its inhibition, contributing to the development of aplastic anemia, leukopenia, neutropenia and thrombocytopenia. The purpose of the study was to study the effect of methotrexate on the state of the leukocyte and megakaryocyte pool of cells in patients with JIA. Material and methods. The study was carried out on the basis of the 2nd City Children's Clinical Hospital in Minsk. A study of the state of hematopoiesis was carried out in 82 children with JIA who received only methotrexate. The comparison group consisted of 40 patients who were diagnosed with JIA and had a complete blood count performed before starting methotrexate therapy. Results. Statistically significant differences were identified in both the megakaryocyte and leukocyte series. Against the background of an increase in the number of platelets before the start of basic therapy, there was a decrease in the average volume of platelets (p<0.01) and, accordingly, the distribution of platelets by volume (p<0.001). Changes in the white blood cell count (WBC) were manifested in a gradual decrease in the number of leukocytes during long-term use of methotrexate (p < 0.001). Conclusion. The use of methotrexate in patients with JIA contributes to a significant decrease in the content of platelets, leukocytes, neutrophils, lymphocytes, and monocytes, which is due to the relief of the inflammatory process. The duration of methotrexate administration did not affect the content of lymphocytes and basophils.

P68 Liver fibrosis is independent of methotrexate use in patients with moderate-to-severe psoriasis

Abstract Methotrexate has been implicated for liver disease in patients with psoriasis for many years. Liver fibrosis (LF) has various established risk factors, but data on the impact of methotrexate on LF in patients with psoriasis are lacking. This cross-sectional cohort study aimed to determine the prevalence of LF using noninvasive LF markers in patients with psoriasis, and to evaluate the relationship between LF and the cumulative dose of methotrexate and other liver disease risk factors. Adults with moderate-to-severe chronic plaque psoriasis diagnosed by a dermatologist, who were selected for a LF assessment, were recruited from dermatology clinics in a tertiary centre between June 2020 and March 2021. Data were recorded as part of standard clinical care and at the time of recruitment. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were used, indicating ≥ mild LF (≥ 7 kPa), ≥ moderate LF (≥ 7.9 kPa) and ≥ advanced LF (≥ 9.5 kPa). Both continuous and categorical LSM values were used for evaluation. A total of 225 patients were included [median age 48, interquartile range (IQR) 37–57, 51% female]. Fifty-six per cent had a body mass index (BMI) ≥ 30 kg m−2, and the median alcohol use disorders identification test (AUDIT) score was 4 (IQR 1–7, 23% score ≥ 8). Ninety-one per cent had received methotrexate for a median duration of 36 months (IQR 14–78). Prevalence rates of LF were 31%, 21% and 13% using LSM ≥ 7 kPa, ≥ 7.9 kPa and ≥ 9.5 kPa, respectively. There was no association between methotrexate and continuous LSM values [unadjusted coefficient 0.16, 95% confidence interval (CI) 0.49–0.82; P = 0.63] or using the categorical LSM cutoff values: 7 kPa (unadjusted coefficient 1.06, 95% CI 0.98–1.15; P = 0.19), 7.9 kPa (unadjusted coefficient 1.03, 95% CI 0.94–1.12; P = 0.58) and 9.5 kPa (unadjusted coefficient 1.01, 95% CI 0.91–1.12; P = 0.84). Similarly, no significant relationship was found when adjusting for other risk factors for LF. The following risk factors were associated with higher LSM values: BMI (P < 0.001), waist circumference (P < 0.001), metabolic syndrome (P < 0.001), AUDIT score (P = 0.020) and Fib-4 score (P = 0.03). This study confirms a high prevalence of significant LF in patients with moderate-to-severe psoriasis. More importantly, it shows that cumulative methotrexate was not associated with LF, and other risk factors including BMI, waist circumference, metabolic syndrome, alcohol intake and Fib-4 score are important predictors for LF. The findings suggest that these risk factors should be assessed in this group of patients to identify patients requiring regular liver health monitoring. Further research is needed to determine whether methotrexate contributes to the progression of LF in the context of pre-existing LF.

Evidence-based efficacy of methotrexate in adult Crohn's disease in different intestinal and extraintestinal indications.

Introduction:Methotrexate (MTX) is included in the therapeutic armamentarium of Crohn’s disease (CD), although its positioning is currently uncertain in an era in which many effective biological drugs are available. No systematic reviews or meta-analysis have stratified the clinical outcomes of MTX according to the specific clinical scenarios of its use.Methods:Medline, PubMed and Scopus were used to extract eligible studies, from database inception to May 2021. A total of 163 studies were included. A systematic review was performed by stratifying the outcomes of MTX according to formulation, clinical indication and criteria of efficacy.Results:The use of MTX is supported by randomized clinical trials only in steroid-dependent CD, with similar outcomes to thiopurines. The use of MTX in patients with steroid-refractoriness, failure of thiopurines or in combination with biologics is not supported by high levels of evidence. Combination therapy with biologics can optimize the immunogenic profile of the biological drug, but the impact on long-term clinical outcomes is described only in small series with anti-TNFα. Other off-label uses, such as fistulizing disease, mucosal healing, postoperative prevention and extraintestinal manifestations, are described in small uncontrolled series. The best performance in most indications was shown by parenteral MTX, favouring higher doses (25 mg/week) in the induction phase.Discussion:Evidence from high-quality studies in favour of MTX is scarce and limited to the steroid-dependent disease, in which other drugs are the leading players today. Many limitations on study design have been found, such as the prevalence of retrospective underpowered studies and the lack of stratification of outcomes according to specific types of patients and formulations of MTX.Conclusion:MTX is a valid option as steroid-sparing agent in steroid-dependent CD. Numerous other clinical scenarios require well-designed clinical studies in terms of patient profile, drug formulation and dosage, and criteria of efficacy.

Prescribing Patterns of Methotrexate in Libyan Patients with Rheumatoid Arthritis

Chronic rheumatoid arthritis (RA) is a systemic inflammatory disease that leads to cartilage and bone erosion. Untreated disease is linked with joint deformity and substantial health care related costs. Conventional disease-modifying anti-rheumatic drugs (DMARDs) are the main tool to treat any form of RA. Methotrexate (MTX) is the key conventional DMARDs. It is recommended as a first-line treatment for patients with RA. However, MTX is potentially associated with various toxicities. No clear pattern of MTX use in patients with RA in Libya, since no national guideline has been implanted so far. The aim was to investigate the prescribing patterns of MTX in Libya. A hundred and twenty patients who were on treatment with MTX and follow up in RA clinic of Tripoli University hospital were evaluated for therapy during the period of 2018 and 2019. Patient distribution data, disease duration, other related diseases and drug prescribed as well as adverse drug reactions were considered to analyze the pattern of drug use. The demographic distribution findings indicate that female patients are more than male patients and the ratio of disease among female to male was 1:9. A range of age between 41 - 60 years was the highest affected compared with other ages. Among of these about 75% of patients were no occupational works. RA related diseases were found to be more with diabetes mellitus, hypertension and osteoporosis. Low use of NSAIDs in this group of patients but with high use of steroid. A high group of patient's use of low dose of MTX for up to five years. This study concludes that MTX is an effective drug in controlling the disease with less and tolerated incidence of side effects.

Methotrexate shows benefit in a subset of patients with severe hidradenitis suppurativa.

BackgroundMethotrexate is an immunomodulatory therapy that may offer benefit to patients with hidradenitis suppurativa (HS). Despite its theoretical advantages, there is a paucity of available data regarding long-term methotrexate use in patients with HS.ObjectiveThis study aimed to assess whether methotrexate treatment leads to improvement in HS disease severity.MethodsWe conducted an institutional review board–approved, single-center, retrospective chart review of patients with HS who were treated with methotrexate between 2000 and 2018. Primary outcome measurements included the HS Physician's Global Assessment (HS PGA), Hurley staging, abscess count, fistula count, and inflammatory nodule count.ResultsA total of 29 patients were identified; 14 were excluded for reasons including never starting methotrexate and missing follow-up data. For remaining patients (n = 15), the average cumulative dose of methotrexate was 520.1 mg (range, 30–1665 mg) and the average length of treatment was 11.7 months (range, 1–38 months). Patients taking methotrexate as a primary therapy had a higher cumulative dose and length of treatment (520.13 mg; 14.6 months) compared with those taking biologics concomitantly (468.44 mg; 9.1 months). Patients using methotrexate as primary therapy demonstrated nonsignificant reductions in HS PGA, inflammatory nodule count, and abscess count. Patients on concomitant biologic therapy failed to demonstrate any change in HS PGA, inflammatory nodule count, and abscess count.LimitationsLimitations of the study include its retrospective nature, small sample size, length of time on methotrexate between groups, and homogeneity of the patient population.ConclusionMethotrexate may represent an effective treatment option in older patients with lower body mass indices but fails to offer benefit in patients taking concurrent biologic therapy.

Japan College of Rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis

Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for treatment of RA in Japan in 1999 at the recommended dose of 6–8 mg/week; it was approved as first-line drug with the maximum dose of 16 mg/week in February 2011. However, more than half of Japanese patients with RA are unable to tolerate a dose of 16 mg/week of MTX. Moreover, some serious adverse events during the treatment with MTX, such as pneumocystis pneumonia (PCP) and lymphoproliferative disorders (LPD) have been observed much more frequently in Japan than in other countries. Therefore, this article, an abridged English translation summarizing the 2016 update of the Japan College of Rheumatology (JCR) guideline for the use of MTX in Japanese patients with RA, is not intended to be valid for global use; however, it is helpful for the Japanese community of rheumatology and its understanding might be useful to the global community of rheumatology.

USE OF METHOTREXATE IN PATIENTS WITH CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

Objective: to compare the efficacy of methotrexate (MTX) and colchicine in patients with chronic arthritis in calcium pyrophosphate crystal deposition disease (CPPDD). Subjects and methods . Data from a controlled prospective cross-sectional study of 10 patients (8 women and 2 men) with chronic arthritis in CPPDD are presented. In the initial period of treatment, all the patients were given colchicine 1 mg/day for 3 months, followed by a wash-out period for 1 month and then subcutaneous MTX 20 mg/week for 3 months. The diagnosis of CPPDD was made if there were calcium pyrophosphate crystals in synovial fluid and signs of chondrocalcinosis, as evidenced by joint X-ray and/or ultrasonography. DAS44, the swollen joint count (SJC) and tender joint count (TJC), pain intensity on a visual analog scale (VAS), the Health Assessment Questionnaire (HAQ) index, and serum C-reactive protein (CRP) levels were determined in all the patients at baseline, 3 months after the beginning of treatment with colchicine, after a wash-out period, and 3 months after the beginning of MTX treatment. Results and discussion . At baseline, mean DAS44 value was 2.47±0.27; SJC and TJC were 2.0±0.6 and 2.4±1.1, respectively; pain intensity was 55.2±12.3 mm; serum CRP level – 3.89±3.82 mg/l; HAQ – 1.1±0.3. Three months after colchicine therapy initiation, mean DAS44 value decreased to 1.76±0.28 (p = 0.004), SJC – to 1.4±0.5 (p = 0.048), TJC – to 1.6±1.35 (p = 0.023), pain intensity – to 42.0±13.2 mm (p = 0.023), CRP level – to 3.13±2.85 mg/l (p = 0.75), HAQ – to 0.95±0.3 (p = 0.041). Good response was achieved in 7 patients after 3 months of colchicine therapy. After the wash-out period, the mean DAS44 value was 2.08±0.26; SJC and TJC – 1.6±0.5 and 1.7±1.4, respectively; pain intensity – 46.5±9.8 mm; CRP level – 3.38±1.74 mg/l; HAQ – 1.3±0.34. Following 3 months of MTX therapy, mean DAS44 value decreased to 1.39±0.45 (p = 0.027), SJC – to 0.7±0.5 (p = 0.023), TJC – to 0.6±0.5 (p = 0.007), pain intensity – to 26.0±18.97 mm (p = 0.045), CRP level – to 2.87±2.06 mg/l (p = 0.75), HAQ – to 0.8±0.6 (p = 0.045). Two of the 3 patients with an insufficient effect of colchicine achieved DAS44 remission after MTX treatment; two patients attained remission after therapy with colchicine and developed an exacerbation of the disease when this drug was replaced by MTX. Conclusion. MTX 20 mg/week is as effective as colchicine in most cases and can be the drug of choice in patients with chronic arthritis in CPPDD if colchicine therapy is ineffective.

Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis

Abstract Objectives To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). Material and method A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. Results MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10–15 mg/m2/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m2/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m2/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. Conclusions This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience.

Gastrointestinal complications of cancer treatment in childhood

Gastrointestinal and liver toxicity are ones of the complications of combined modality treatment for malignant tumors in childhood. Issues of gastrointestinal complications after radiation therapy and chemotherapy are considered in article. We describe the clinical presentation, diagnosis and treatment of diseases and syndromes associated with the effects of the specific treatment. Among infectious complications accented reader's attention to such serious complication such as cryptosporidiosis, cytomegalovirus infection, and viral hepatitis B and C. Described in detail the clinical pattern of cytomegalovirus hepatitis and enterocolitis. The most common effects of abdominal irradiation are post-radiation enteritis and venoocclusive disease, the occurrence of which is associated with concomitant use of cytotoxic drugs and radiation the liver. Often the development of hepatotoxicity is associated with high-dose chemotherapy with allogeneic or autologous stem cell transplantation, as well as prolonged use of methotrexate in patients with acute lymphoblastic leukemia at the stage of maintenance therapy. The article describes the phase drug metabolism in the liver and pathogenesis of disorders. This article lists the chemotherapy agents, the use of which in the schemes of chemotherapy can induce the development of hepatocellular toxicity. Recommendations for dispensary observation and examination of patients with identified disorders of the gastrointestinal and hepato-biliary system.

Recomendaciones para el uso de metotrexato en pacientes con artritis idiopática juvenil

ObjectivesTo develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). Material and methodA group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. ResultsMTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15mg/m2/week. In cases of uveitis or polyarthritis, an initial dose of 15mg/m2/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15mg/m2/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. ConclusionsThis document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience.

Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis

The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases. The literature published between 2008 and 2012 was systematically reviewed and updated recommendations on MTX use in rheumatic diseases, particularly RA, were formulated. These recommendations were approved by a panel of expert Italian Rheumatologists. A total of 10,238 references were identified, among which 70 studies were selected for critical evaluation. Sufficient evidence had accumulated to warrant changes to several of the recommendations in the new version. A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed.

Canadian Recommendations for Use of Methotrexate in Patients with Rheumatoid Arthritis

To develop recommendations for the use of methotrexate (MTX) in patients with rheumatoid arthritis. Canadian rheumatologists who participated in the international 3e Initiative in Rheumatology (evidence, expertise, exchange) in 2007-2008 formulated 5 unique Canadian questions. A bibliographic team systematically reviewed the relevant literature on these 5 topics. An expert committee consisting of 26 rheumatologists from across Canada was convened, and a set of recommendations was proposed based on the results of systematic reviews combined with expert opinions using a nominal group consensus process. The 5 questions addressed drug interactions, predictors of response, strategies to reduce non-serious side effects, variables to assess clinical response, and incorporating patient preference into decision-making. The systematic review retrieved 93 pertinent articles; this evidence was presented to the expert committee during the interactive workshop. After extensive discussion and voting, a total of 9 recommendations were formulated: 2 on drug interactions, 1 on predictors of response, 2 on strategies to reduce non-serious side effects, 3 on variables to assess clinical response, and 1 on incorporating patient preferences into decision-making. The level of evidence and the strength of recommendations are reported. Agreement among panelists ranged from 85% to 100%. Nine recommendations pertaining to the use of MTX in daily practice were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement.

Tratamiento secuencial de la neumonitis intersticial asociada con polimiositis

Polymyositis is a chronic inflammatory disease of the striated muscles that may frequently affect the lung, with the possibility of causing diffuse interstitial lung disease. Non-specific interstitial pneumonia is generally the most frequent histological findings found in this condition. In general, the recommended treatment for interstitial lung disease associated with polymyositis is prednisone together with an immunosuppressant. However, there is insufficient agreement on the initial therapeutic regime and on the best immunosuppressant. In the treatment of polymyositis, a combination of prednisone and methotrexate is recommended. However, experts in this field advise against the use of methotrexate in patients with reduced pulmonary reserve due to its potential toxicity on the lung. We present a case of non-specific interstitial pneumonia associated with polymyositis, whose pulmonary alterations were solved with prednisone. After, methotrexate was added as maintenance treatment, without observing adverse effects. Our results agree with the opinion of the authors who recommend initially treating these patients with high doses of corticosteroids in monotherapy. This option may solve the pulmonary alterations and allow us to use methotrexate as a potential candidate for the maintenance treatment. The resolution of pneumonia with corticosteroids would improve the tolerance of the patient in face of the development of a possible pulmonary toxicity induced by the immunosuppressant.

Treatment of Vulvovaginal Erosive and Stenosing Lichen Planus by Surgical Dilatation and Methotrexate

Mucosal lichen planus (LP) is a rare variant of LP, itself a common skin disorder. Two-thirds of those affected have an erosive form of LP that causes severe vulvovaginal and, in some cases, oral mucosal symptoms, including burning, pain, and pruritus. The disease affects the vaginal orifice and often, the labia minora. Patients present with erythematous, partly erosive, desquamative lesions that may have a pale border. Erosive LP is thought to be an autoimmune disorder. In time, vulvovaginal LP causes scarring and narrowing of the vagina. Treatment of vulvovaginal LP has proved to be challenging. The authors report 5 women with severe symptoms of vulvar scarring and resultant stenosis or obliteration of the vagina, all of whom responded, at least in part, to treatment with surgical dilatation, methotrexate, and local preparations such as tacrolimus and a potent steroid cream. Methotrexate, given in a weekly dose of 7.5 mg, also benefited oral lesions. Stenotic changes decreased during methotrexate therapy, suggesting that it be started as soon as possible after surgical dilatation of the vagina. Topical steroids proved helpful in some patients having exacerbations of the disorder. Tacrolimus, a topical immunosuppressant, is active against vulvar LP and has helped to prevent narrowing of the vulva and vagina in patients failing to respond to a potent local steroid. Local treatment with pimecrolimus and cyclosporin has reportedly been effective. In addition, patients were asked to wash the genital area with emollients, and local estrogen treatment was given to prevent vaginal atrophy. In the present patients, methotrexate appeared to exert positive effects even after it was discontinued. The only adverse side effect was hair loss in 1 patient. All the women took folic acid while receiving methotrexate. This experience endorses the use of low-dose methotrexate in patients with severe stenosing vulvovaginal LP if surgical dilatation and local treatment have failed. It should be continued until symptoms have resolved, and may be d if the disorder recurs. These patients require close follow-up because of the possibility that vulvar LP will undergo malignant transformation.

A Survey of Canadian Gastroenterologists about the Use of Methotrexate in Patients with Crohn’s Disease

Methotrexate (MTX) is effective in remission induction and maintenance in steroid-dependent Crohn's disease (CD), but is often considered to be a second-line immunosuppressive agent, to be used in cases of failure or intolerance to azathioprine (AZA) or 6-mercaptopurine (6-MP). This may be related to concerns about hepatotoxicity, but this adverse effect is rare in monitored CD patients taking MTX. Still, there are no guidelines for monitoring patients with CD on MTX, and physicians must decide based on rheumatological literature about how to monitor their patients. To determine the patterns of MTX use in patients with CD by Canadian gastroenterologists, examining the reasons for choosing MTX versus AZA/6-MP, the doses and routes of administration of MTX, and how patients on MTX are monitored, including the use of liver biopsy. A self-report survey was sent to physician members of the Canadian Association of Gastroenterology, with a second mailing three months later to increase response rate. Of 490 surveys mailed, a 54.9% response rate was achieved. Of adult gastroenterologists, 60.7% stated they never use MTX as a first-line immunosuppressive agent, and 33.3% never use MTX at all. The most common reasons for choosing MTX were a contraindication to the use of AZA/6-MP (43.7%) and patient preference (22.5%). MTX is used intramuscularly in 41.5%, subcutaneously in 31.8%, and orally in 26.7% of patients. The most common dose used for remission induction was 25 mg/week (84.2%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly) and for remission maintenance was 15 mg/week (55.4%; range 7.5 mg/week to 50 mg/week; three responders used more frequent dosing than weekly). Most responders checked a liver profile and complete blood count at baseline and serially. Of those who used MTX, 26.5% routinely performed liver biopsy after an accumulated dose of MTX had been taken (usually 1 g to 2 g), 57.7% sometimes performed liver biopsy, and 16.8% never performed liver biopsy. Of pediatric gastroenterologists, 17.6% never used MTX, but those who used it prescribed it subcutaneously (80.0%) more often than intramuscularly (17.5%) or orally (2.5%). MTX was used as a first-line immunosuppressive agent in patients with CD by a minority of Canadian gastroenterologists. When used, there is variability in how MTX is prescribed and monitored. Although hepatotoxicity is rare, liver biopsy was performed frequently and probably often unnecessarily.

Conservative treatment of ectopic pregnancies: Comparison of velocity of decrease of beta-hcg between spontaneous and methotrexate induced resorptions

The evolution of the process can take two different directions. If an Intact pregnancy continues to grow, there is a tubal abortion or a rupture of the Fallopian tube. In the oppsote case, there is spontaneous resorption of the tubal pregnancy. In certain cases with the application of methotrexate, the ectopic pregnancy growth can be interrupted and spontaneous resorption can be induced. Nowadays, the international standards of treating patients with early ectopic gravidities and no peritoneal effusions, with beta-HCG values below 6000 UI/l, gestational sac diameter below 3 cm, and without any visible heart action, imply methotrexate treatment. The objective of this study is to prove the efficiency of methotrexate use in patients who meet the above criteria. The first group did not manifest satisfying decrease of [beta-HCG after two measurements, so methotrexate was used, while the second group showed satisfying decrease of beta-HCG, measured on the third day. Comparing the velocity of decrease of beta-HCG level among both groups of patients, it was proved that iatrogenically induced decrease, that is to say the achieved resorption, was equal to the spontaneous resorption, which justified the use of methotrexate in ectopic pregnancy treatment.

Current Thoughts on the Use of Methotrexate in Patients with Psoriasis

Background: There are many problems associated with the use of methotrexate in the treatment of psoriasis. Objective: We will attempt to assist the clinician in resolving some of these problems. Methods: This article is a summary of a Round Table Discussion on methotrexate held at the Canadian Dermatology Association meeting at Whistler, BC, July 1995; of a Continuing Medical Education meeting on methotrexate at Langdon Hall, Cambridge, ON, May 1996; and our review of the pertinent literature. Results: We recommend routine folic acid supplementation in patients receiving methotrexate. A baseline pretreatment liver biopsy is probably not indicated in patients without clinical or laboratory evidence of liver disease; and patients on 15 mg or less of methotrexate per week with normal liver function may not need liver biopsy. Conclusion: Liver biopsy of patients on methotrexate for psoriasis may not be necessary.

The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis: The results of a pilot study

Ursodeoxycholic acid (UDCA) and methotrexate (MTX) have both been proposed as treatments for patients with primary biliary cirrhosis (PBC). It has been suggested that a combination of the two drugs may offer advantages over either used separately. In this pilot study, we sought to evaluate the safety and efficacy of this combination for patients with PBC. Thirty-two patients with antimitochondrial antibody positive PBC were prospectively entered into a pilot study and received UDCA, 13 to 15 mg/kg/d, in conjunction with MTX, 0.25 mg/kg/wk, for a period of 2 years. The results of this treatment were compared with those obtained from 180 patients with PBC studied in a placebo-controlled trial of UDCA alone conducted during the same period. Patients in the pilot study and randomized study were comparable with regard to age, gender, and liver biochemistries. The UDCA/MTX-treated patients were of earlier histologic stage and had a lower mean Mayo risk score. During this period, seven patients in the UDCA/MTX group were withdrawn, four for pulmonary toxicity (two who required hospitalization), and one each with mouth ulcer, extreme fatigue, and hair loss. The use of UDCA/MTX was not associated with improvement in symptoms. In the patients receiving UDCA/MTX, biochemical changes were comparable to those of patients receiving UDCA alone but superior to those in the placebo group (P < .05). Histological changes were comparable in all groups at 2 years. Cessation of MTX while UDCA was continued led to no deterioration in liver biochemistries. In a 2-year study, the use of MTX in combination with UDCA was associated with substantial toxicity, but with no evidence for symptomatic, biochemical, or histologic improvement over that seen with UDCA alone. The use of MTX in patients with PBC should be confined to pa- tients in prospective trials and not used on an empiric basis. (HEPATOLOGY 1995; 22:1158–1162.).

A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis

Background/Aims: Primary sclerosing cholangitis (PSC) is a progressive disease with no accepted effective treatment. Because methotrexate was associated with clinical and histological improvement in two men with PSC, we conducted a prospective trial of methotrexate in PSC. Methods: A prospective placebo-controlled, double-blind trial of methotrexate in PSC was performed. Twenty-four patients with PSC were randomized to receive methotrexate or placebo for a 2-year period. Seven of 12 taking methotrexate and five taking placebo had cirrhosis. Serial liver biopsies, endoscopic retrograde cholangiopancreatography (ERCP), and biochemical tests of liver function were followed. Results: There were no significant changes in liver histological results, ERCP findings, tests of liver function (other than alkaline phosphatase), or outcome between the two groups. Mean alkaline phosphatase levels decreased by 152 IU in the methotrexate group and increased by 30 IU in the placebo group (P = 0.032). Patients taking methotrexate were more likely to reduce or discontinue cholestyramine than patients taking placebo. Conclusions: This study does not support efficacy for methotrexate in the treatment of PSC. On the basis of this study, the empiric use of methotrexate in patients with PSC is not recommended. However, methotrexate is being further evaluated in patients with precirrhotic PSC.

Methotrexate and Psoriasis

To the Editor.— The editorial ( 212 : 314, 1970) on psoriasis, methotrexate, and cirrhosis presents a cogent and balanced approach to the treatment of a patient with a long-term and recurrent problem. We feel that one statement (... are expanding to include milder degrees of involvement where only cosmetic inconvenience exists) may be open to misinterpretation. The Food and Drug Administration (FDA) approved the use of methotrexate in 1959 for treatment of certain neoplastic disease. Recently a warning statement concerning the risk of hepatoxicity during chronic administration was added to the package insert. We limit the term indications to uses approved by FDA. An application which had been submitted to the FDA providing for the use of methotrexate in patients with severe recalcitrant psoriasis was withdrawn one year ago; we are now awaiting the completion and submission of pharmacologic studies establishing the safety of chronic use and clinical studies developing dosage