Tolerability Of Methotrexate Research Articles

Treatment with Targeted Therapy in Patients with Psoriatic Arthritis and Inadequate Response to Methotrexate: Proposal for a Rational Strategy.

The therapeutic arsenal for psoriatic arthritis (PsA) is gradually being expanded, but the use of these targeted treatments must be optimal. Our objective was to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom methotrexate (MTX) has failed. We searched for literature data in PubMed with the appropriate keywords for the six points of our argument: (1) the tolerance of MTX; (2) the efficacy of targeted therapies combined with MTX vs monotherapy; (3) immunogenicity of anti-tumor necrosis alpha (TNFα) monoclonal antibodies (mAbs); (4) immunogenicity of anti-interleukin (IL)-17, anti-IL-12/23, and anti-IL-23 mAbs; (5) the therapeutic maintenance of anti-TNFα mAbs when combined or not with MTX; (6) the therapeutic maintenance of anti-IL-17 vs anti-TNFα mAbs as first-line targeted therapy. The proposed rational strategy is as follows: in case of initiation of an anti-TNFα agent, maintaining treatment with MTX seems preferable, even in the absence of evidence of the superior efficacy of the combination, to avoid immunization and reduced therapeutic maintenance; in case of initiation of anti-IL-17, anti-IL-12/23, anti-IL-23 agents, or Janus kinase (JAK) inhibitors, again in the absence of evidence of the superior efficacy of the combination, discontinuing MTX therapy may be possible, at least in two steps, after verifying the efficacy of the targeted therapy initiated on the joints and skin. We have data from the literature to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom MTX has failed.

Efficacy and tolerance of methotrexate in a real-life monocentric cohort of patients with giant cell arteritis

ObjectivesTo assess the indications, efficiency and tolerance profiles of methotrexate (MTX) in patients with giant cell arteritis (GCA) in a real-life setting. MethodsFrom a monocentric database of >500 GCA patients, we retrospectively selected 49 patients who received MTX between 2010 and 2020. Cumulative glucocorticoid (GC) doses, the number of relapses and GC-related adverse events were recorded before, during and after MTX. We separately analyzed the 3 main indications of MTX, i.e., disease relapse, GC-sparing strategy, and GCA presentation. ResultsWith a median follow-up of 84 [10–255] months, 25 (51%) and 18/41 (44%) patients relapsed during MTX treatment and after its discontinuation, respectively. Among the 40 patients who relapsed before MTX, 26 (65%) experienced a new relapse after MTX introduction. Once MTX was introduced, 24 (49%) patients were able to discontinue GC after 20.5 [7–64] months. No significant difference in cumulative GC doses were noted before and after MTX introduction with a total GC dose of 14.7 [1.05–69.4] grams. At the last follow-up, MTX was discontinued in 41 patients, including 13 (32%) due to clinicobiological remission, 12 (30%) due to treatment failure and 15 (36%) due to side effects. ConclusionOur real-life study showed a modest beneficial effect of MTX on relapse in patients with GCA. However, we did not observe any GC-sparing effect in this study. Other studies are needed to assess the GC-sparing effect in patients in whom GC management is adapted from recent recommendations.

Efficacy of Methotrexate Alone vs Methotrexate Plus Low-Dose Prednisone in Patients With Alopecia Areata Totalis or Universalis

Poor therapeutic results have been reported in patients with alopecia areata totalis (AT) or universalis (AU), the most severe and disabling types of alopecia areata (AA). Methotrexate, an inexpensive treatment, might be effective in AU and AT. To evaluate the efficacy and tolerance of methotrexate alone or combined with low-dose prednisone in patients with chronic and recalcitrant AT and AU. This academic, multicenter, double-blind, randomized clinical trial was conducted at 8 dermatology departments at university hospitals between March 2014 and December 2016 and included adult patients with AT or AU evolving for more than 6 months despite previous topical and systemic treatments. Data analysis was performed from October 2018 to June 2019. Patients were randomized to receive methotrexate (25 mg/wk) or placebo for 6 months. Patients with greater than 25% hair regrowth (HR) at month 6 continued their treatment until month 12. Patients with less than 25% HR were rerandomized: methotrexate plus prednisone (20 mg/d for 3 months and 15 mg/d for 3 months) or methotrexate plus placebo of prednisone. The primary end point assessed on photos by 4 international experts was complete or almost complete HR (Severity of Alopecia Tool [SALT] score <10) at month 12, while receiving methotrexate alone from the start of the study. Main secondary end points were the rate of major (greater than 50%) HR, quality of life, and treatment tolerance. A total of 89 patients (50 female, 39 male; mean [SD] age, 38.6 [14.3] years) with AT (n = 1) or AU (n = 88) were randomized: methotrexate (n = 45) or placebo (n = 44). At month 12, complete or almost complete HR (SALT score <10) was observed in 1 patient and no patient who received methotrexate alone or placebo, respectively, in 7 of 35 (20.0%; 95% CI, 8.4%-37.0%) patients who received methotrexate (for 6 or 12 months) plus prednisone, including 5 of 16 (31.2%; 95% CI, 11.0%-58.7%) who received methotrexate for 12 months and prednisone for 6 months. A greater improvement in quality of life was observed in patients who achieved a complete response compared with nonresponder patients. Two patients in the methotrexate group discontinued the study because of fatigue and nausea, which were observed in 7 (6.9%) and 14 (13.7%) patients receiving methotrexate, respectively. No severe treatment adverse effect was observed. In this randomized clinical trial, while methotrexate alone mainly allowed partial HR in patients with chronic AT or AU, its combination with low-dose prednisone allowed complete HR in up to 31% of patients. These results seem to be of the same order of magnitude as those recently reported with JAK inhibitors, with a much lower cost. ClinicalTrials.gov Identifier: NCT02037191.

Glabridin Plays Dual Action to Augment the Efficacy and Attenuate the Hepatotoxicity of Methotrexate in Arthritic Rats.

Glabridin is chemically an isoflavane class of natural phenols and is found mainly in the roots of Glycyrrhiza glabra. It has several beneficial pharmacological actions for the management of inflammatory disorders as well as can counteract drug-induced toxic effects. On the other hand, methotrexate (MTX) is the first-line disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. However, its treatment is associated with major side effects like hepatotoxicity. In the quest to explore a suitable combination therapy that can improve the efficacy and reduce the hepatotoxicity of MTX, we hypothesized that glabridin might serve the purpose for which there is no literature precedent to date. We explored the antiarthritic efficacy of MTX in the presence or the absence of glabridin using Mycobacterium-induced arthritic model in rats. The results of reduction in paw swelling, inhibition of serum cytokines (TNF-α, IL-6, and IL-1β), and improvement in the bone joints from radiological and histopathological findings suggest that glabridin can substantially augment the antiarthritic efficacy of MTX. Further, results of concomitant glabridin treatment with MTX in the experimental time frame demonstrate that glabridin could considerably prevent the MTX-induced hepatic alteration in serum biochemical markers (SGPT and SGOT) and oxidative stress markers (malondialdehyde (MDA) and glutathione reduced (GSH)). Moreover, glabridin showed a marked effect in impeding the regulation of NF-κB/IκBα and Nrf2/Keap1 pathways in the hepatic tissues. The results of simultaneous administration of glabridin with MTX in the rat model indicate that glabridin had no pronounced effect of causing severe alteration in the pharmacokinetic behavior of MTX. In summary, glabridin can significantly potentiate the antiarthritic efficacy of MTX and can also minimize its hepatotoxicity via the inhibition of inflammation and oxidative stress. Further research should be performed to develop glabridin as a phytotherapeutics for the improved efficacy and better tolerability of MTX at the reduced dose level of MTX.

Efficacy and Tolerability of Methotrexate in the Treatment of Severe Paediatric Alopecia Areata

Introduction: Alopecia areata (AA) is a chronic, autoimmune condition affecting hair follicles, and its occurrence in the paediatric population is associated with poorer prognosis and limited treatment options compared to adults. Treatment with oral methotrexate (MTX) has been documented in adults, but there is a paucity of data for its use in the paediatric population. We aimed to study the efficacy and tolerability of MTX in severe paediatric AA. Methods: We performed a retrospective review on paediatric patients with severe AA who were treated with MTX in our centre from January 2019 to December 2020. Results: Thirteen patients were included (6 boys and 7 girls) aged between 4 and 16 years at the initiation of MTX (mean age of 8.8 years). The interval from diagnosis of AA to commencement of MTX was between 8 months and 9 years (mean duration of 3.3 years). Oral MTX was administered once weekly with a mean maximal dose of 0.4 mg/kg/dose. Out of 12 assessable patients, 5 were considered treatment success as they had more than 50% regrowth, while the other 7 were treatment failures. No serious side effects were reported. Conclusion: MTX was shown to have variable efficacy for the treatment of paediatric AA with overall good tolerability. MTX can be considered in the treatment of severe refractory AA for children.

Efficacy and tolerability of methotrexate at a dose of 15 mg/week and 10 mg/week in patients with pulmonary sarcoidosis

The objective of this study is to conduct a comparative study of the efficacy and safety of methotrexate (MT) at a dose of 10 mg/week and 15 mg/week in patients with pulmonary sarcoidosis having contraindications to GCS therapy. Material and Methods. The study involved 44 patients with stage II pulmonary sarcoidosis (26 females and 18 males aged 24 to 70) with contraindications to the appointment of therapy glucocorticosteroid (GCS). In group 1 (28 patients), methotrexate was prescribed at a dose of 10 mg/week, in group 2 (16 patients), methotrexate was prescribed at a dose of 15 mg/week. The diagnosis and assessment of the dynamics of sarcoidosis were carried out taking into account clinical symptoms based on the results of high-resolution computed tomography and body plethysmography. The significance of differences in indicators was determined using the Student's t-test and Fisher's exact test. The number of cases of clinical treatment without residual changes of a fibrous nature in the lung parenchyma in patients after treatment with methotrexate at a dose of 15 mg/week significantly increased compared to the same indicator in the group of patients after treatment at a dose of 10 mg/week (81.3% and 42.4% respectively, p=0.025). An increase in the therapeutic dose of methotrexate from 10 mg/week to 15 mg/week leads to a decrease in the time to achieve a clinical cure (10.1±0.5 months and 12.8±0.8 months respectively, р˂0.02), indicating an accelerating rate of regression of sarcoidosis. Immunosuppressive therapy of patients with pulmonary sarcoidosis using the drug at doses of 10 and 15 mg/week is characterized by satisfactory tolerability.

P024 Efficacy and tolerance of methotrexate in patients with Juvenile Idiopathic Arthritis

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease for children. The therapeutic management depends on several factors and is based on different treatments including methotrexate (MTX). The aim of our study was to determine the efficacy and safety of MTX in JIA. Methods This is a monocentric retrospective study of 37 patients followed for JIA according to the 2001 International League of Association of Rheumatology (ILAR) criteria and treated with MTX. Socio-demographic, clinical, paraclinical and therapeutic data were collected. Disease activity was assessed by the JADAS score. Highly active JIA was defined as JADAS superior to 25. Results There were 25 boys (67.5%) and 12 girls (32.4%) with a median age of 6.3 years [4–13]. The average duration of the rheumatic disease was 2.7 years [2.5–5.3]. The type of JIA was: oligoarticular in 22 cases (59.4%), polyarticular in 10 cases (27%), arthritis related to enthesitis in 3 cases (8.1%) and systemic in 2 cases (5.4%). Twenty patients (54%) received oral corticosteroid therapy for a mean period of 1.7 years [0.6–3] with a mean daily dose of 10 mg/day of prednisone or equivalent. Oral MTX was prescribed to all patients with a mean weekly dose of 10 mg/m2 body surface [10–15]. MTX was initiated after a mean period of 6.2 months [3.1–11.4] from diagnosis. The mean treatment duration was 50 months [34–66]. Observance of MTX was 80.5%. Remission with MTX was achieved in 28 patients (75.6%) after a mean treatment duration of 7.5 months [5–11], with a mean JADAS of 5.1 [3.5–10]. Despite good observance of MTX, eight patients (21.6%) continued to have high disease activity with a mean JADAS score of 32 [25–40]. Tolerance to oral MTX was good, with side effects occurring only with 5 patients (13.5%), such as epigastralgia in 2 cases (which disappeared after switching to the intramuscular administration), a skin reaction in one case, and hepatic cytolysis reversible when stopping the treatment in 2 other cases. Conclusion MTX still has a place in the therapeutic management of JIA and appears to be a well-tolerated and effective treatment.

The Wonderful DMARD with Multiple Toxicities

Methotrexate is a type of disease-modifying anti-rheumatic drug (DMARD). It is used to reduce activity of the immune system for people who have certain conditions. Methotrexate is a chemotherapy agent and immune system suppressant. Its use may be limited by concerns regarding its adverse reactions. The occurrence of adverse drug reactions in some cases leads to the therapy discontinuation. Although adverse drug reactions (ADR) of methotrexate generally do not pose a serious threat to the health of patients and a reduction in the dose of methotrexate leads to their elimination, in some cases severe toxicities of the drug occur unpredictably. These facts explain the need for close monitoring of the patient’s condition and the identification of potential risk factors for drug toxicity on the part of different organs and functional systems. The purpose of this review is to detail about safety and tolerability of methotrexate.

Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma.

Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

Efficacy and Tolerability of Methotrexate and Methylprednisolone in a Comparative Assessment of the Primary and Long-Term Outcomes in Patients with Pulmonary Sarcoidosis.

Background: There is insufficient information in the literature on the comparative efficacy and tolerability of methotrexate (MTX) and methylprednisolone (MP) in patients with pulmonary sarcoidosis in assessing primary outcomes and the relapse rate. Purpose: The aim of our study was to evaluate primary and long-term outcomes of using MTX and MP in patients with pulmonary sarcoidosis. Methods: A total of 143 patients with newly diagnosed pulmonary sarcoidosis, verified by high-resolution computed tomography (CT) data, were examined. Corticosteroid (CS) therapy was used in 97 patients using MP at a dose of 0.4 mg/kg body weight for 4 weeks, followed by a dose reduction to 0.1 mg/kg by the end of the sixth month. The total duration of CS therapy was 12 months on average. Forty-six patients were treated with MTX at a dose of 10 mg/week (28) and 15 mg/week (18) per os for 6 to 12 months. The study of the relapse rate was conducted within 12 months after the CT data normalization in 60 patients after CS therapy and in 24 after MTX treatment. Results: MP treatment was successfully completed in 68 (70.1%), and MTX in 29 (60.4%) patients. In five MP patients (5.2%) and in five (10.9%) MTX, treatment was discontinued due to serious side effects. In seven (7.2%) MP patients and ten (21.7%) MTX patients, treatment required additional therapy due to the lack of efficacy. Progression with MP treatment (17–17.5%) was more common than with MTX (2–4.3%; Chi square = 4.703, p = 0.031). Relapses after MP therapy were observed in 26 (43.3%) patients, and after MTX therapy in 2 (8.3%; Chi square = 9.450, p = 0.003). Conclusion: In patients with pulmonary sarcoidosis, MTX monotherapy does not differ significantly from MP monotherapy in terms of the level of efficacy and the rate of serious side effects. Increasing the MTX dose from 10 to 15 mg/week accelerates the rate of regression of sarcoidosis, improves treatment efficacy, and does not affect the rate of serious side effects. When using MTX, there is a significant decrease in the incidence of treatment resistance and the relapse rate.

Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study

BackgroundTreatment of pulmonary sarcoidosis is recommended in case of significant symptoms, impaired or deteriorating lung function. Evidence-based treatment recommendations are limited and largely based on expert opinion. Prednisone is currently the first-choice therapy and leads to short-term improvement of lung function. Unfortunately, prednisone often has side-effects and may be associated with impaired quality of life. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects.ObjectiveThe primary objective of this trial is to investigate the effectiveness and tolerability of methotrexate as first-line therapy in patients with pulmonary sarcoidosis compared with prednisone. The primary endpoint of this study will be the change in hospital-measured Forced Vital Capacity (FVC) between baseline and 24 weeks. Secondary objectives are to gain more insights in response to therapy in individual patients by home spirometry and patient-reported outcomes. Blood biomarkers will be examined to find predictors of response to therapy, disease progression and chronicity, and to improve our understanding of the underlying disease mechanism.Methods/designIn this prospective, randomized, non-blinded, multi-center, non-inferiority trial, we plan to randomize 138 treatment-naïve patients with pulmonary sarcoidosis who are about to start treatment. Patients will be randomized in a 1:1 ratio to receive either prednisone or methotrexate in a predefined schedule for 24 weeks, after which they will be followed up in regular care for up to 2 years. Regular hospital visits will include pulmonary function assessment, completion of patient-reported outcomes, and blood withdrawal. Additionally, patients will be asked to perform weekly home spirometry, and record symptoms and side-effects via a home monitoring application for 24 weeks.DiscussionThis study will be the first randomized controlled trial comparing first-line treatment of prednisone and methotrexate and provide valuable data on efficacy, safety, quality of life and biomarkers. If this study confirms the hypothesis that methotrexate is as effective as prednisone as first-line treatment for sarcoidosis but with fewer side-effects, this will lead to improvement in care and initiate a change in practice. Furthermore, insights into the immunological mechanisms underlying sarcoidosis pathology might reveal new therapeutic targets.Trial registrationThe study was registered on the 19th of March 2020 in the International Clinical Trial Registry, www.clinicaltrials.gov; ID NCT04314193.

What do we know about the possibility of predicting the potential efficacy and safety of methotrexate, by measuring the concentration of its metabolites in rheumatoid arthritis?

Rheumatoid arthritis (RA) is characterized by a progressive course with the formation of joint deformities and the development of severe functional disorders. The most favorable conditions for changing the course of the disease emerge in the first months after its onset. Methotrexate (MTX) occupies a leading position in the treatment of RA. There is a need to develop tools that will be able to predict the efficacy and tolerability of MTX at the earliest stages of RA treatment. The concentration of active metabolites of MTX is considered as a potential biomarker that enables one to predict what response to therapy with this drug will be.The paper analyzes the most relevant works devoted to the study of the concentration of active MTX metabolites polyglutamates (MTX PGs) in patients with RA. It is shown that the presented studies do not cover all the possibilities of therapeutic drug monitoring, in particular the determination of the levels of MTX PGs in mononuclear cells over time. Further investigation is needed to develop an objective approach to prescribing MTX in RA patients.

Effectiveness and tolerability of methotrexate in pulmonary sarcoidosis: A single center real-world study.

Pulmonary sarcoidosis patients who get disease progression despite corticosteroid treatment or can't tolerate corticosteroid required second-line drug. Methotrexate (MTX) is the most widely used in our clinical practice. Data on its safety and efficacy at different doses are still limited, especially for those without folic acid supplements. To report effectiveness of different MTX dosages and tolerability of MTX in pulmonary sarcoidosis without folic acid supplements. A retrospective study on pulmonary sarcoidosis patients receiving MTX therapy with various dose ≥3 months was conducted. The primary outcome was change in high-resolution computed tomography (HRCT) before and after MTX therapy. Other efficacy parameters included SGRQ score, prednisone dose change, discontinuation and relapse-free survival. Response-linked factors and safety outcomes were also analyzed. Overall, 49 patients (81.7%) were assessed as MTX responders by HRCT and there was no significant difference in clinical response rate among three groups with different doses. The health-related quality of life (HRQL) of the responders improved obviously, which was evidenced by SGRQ score declining from 16.7(IQR: 7.9-26.4) to 10.7(IQR: 4.8-19.3) (P=0.029). The corticosteroids sparing effect was confirmed in "responders" group (P<0.001). When MTX was discontinued in 11 responders with complete improvement, 2 patients experienced relapses within 15.5 (range: 1-30) months (mean follow-up time of these 11 responders: 13.5±13.0 months). No clinical characteristics were found related to MTX effectiveness. Adverse events occurred in 31.7% of the patients, with gastrointestinal-related being the commonest. Drug discontinuation owing to adverse events occupied 6.7% of the subjects. Nearly 80% of the sarcoidosis subjects had well response to MTX. Its effectiveness was irrelevant to the treatment dosages and baseline characteristics. A quite low relapse rate was witnessed in those complete responders discontinuing MTX therapies. The steroid-sparing effect, well drug tolerability and low drug withdrawal rate were observed in these patients even without folic acid supplements in clinical practice.

Effectiveness, Safety and Tolerance of Methotrexate in Vietnamese Psoriatic Arthritis Patients

AIM:To access the effectiveness, safety and tolerance of methotrexate (MTX) in psoriatic arthritis (PsA) treatment.METHODS:We recruit 37 patients, admitted at HCMC Hospital of Dermato-Venereology from 1/2016 to 3/2017, with MTX dosage ranging from 10 mg to 15 mg per week.RESULTS:Skin lesion response after 12 weeks improved PASI 50: 40.5%, PASI 75: 24.3%. Disease activity score decreased after 12 weeks with ∆DAS28 = -1.43 + 0.79, 37.8% PsA achieved complete remission. Nausea and vomiting were 8.1%. These symptoms were mild and transient. We did not stop MTX usage. The rate of elevating SGPT 2-3 times as much as the upper limit of the normal range was 2.7%.CONCLUSION:We finally demonstrated that the rate of treatment response in Vietnam is the same as demonstrated by foreign authors in other countries.

Tolerance of methotrexate in a daily practice cohort of adults with atopic dermatitis.

Tolerance of methotrexate in a daily practice cohort of adults with atopic dermatitis.

Methotrexate use in allergic contact dermatitis: a retrospective study.

Methotrexate, a folate antimetabolite, is used to treat atopic dermatitis and psoriasis. Although methotrexate's therapeutic efficacy has been noted in the literature, there are few data on the efficacy of methotrexate treatment for allergic contact dermatitis. To evaluate the efficacy and tolerability of methotrexate in treating allergic contact dermatitis at a single institution, and also to assess methotrexate efficacy in patients with chronic, unavoidable allergen exposure. We performed a retrospective chart review of 32 patients diagnosed with allergic contact dermatitis by positive patch test reactions, and who received treatment with methotrexate from November 2010 to November 2014. Demographic and treatment-associated data were collected from electronic medical records. Ten patients were identified as allergen non-avoiders secondary to their occupation, and were subgrouped as such. Seventy-eight per cent (25/32) of patients showed either a partial or a complete response. Methotrexate had a comparable efficacy rate in the allergen non-avoiders subset, at 10 of 10. Of the 32 patients, 23% (5/22) had complete clearance of their dermatitis, and 1/10 of allergen non-avoiders had complete clearance of their dermatitis. Methotrexate is a well-tolerated and effective treatment for allergic contact dermatitis, and shows comparable efficacy to immunomodulatory agents such as cyclosporine and azathioprine, with robust efficacy despite persistent allergen exposure in patients with allergic contact dermatitis.

The efficacy of methotrexate in the treatment of en coup de sabre (linear morphea subtype)

Background: En coup de sabre is a rare subtype of linear morphea, located on the forehead or frontoparietal scalp. Systemic treatment of localised morphea with methotrexate has been reported in a few clinical reports. However, there are no case series using methotrexate treatment for En coup de sabre.Objective: To evaluate the efficacy and tolerability of methotrexate in the treatment of en coup de sabre linear morphea subtype.Method: A retrospective chart review was performed for paediatric and the adult patients with en coup de sabre evaluated in the Dermatology Clinic at Wake Forest University School of Medicine treated with methotrexate.Results: There were 7 patients who met criteria for inclusion in the study. The mean age at the onset of disease was 11.8 years (ranging from 4 to 38 years). The mean duration of disease before receiving methotrexate therapy was 9.4 months (ranging from 3 to 24 months). Seven (100%) patients improved with methotrexate therapy, in an average of 2 months to disease inactivity, and 16 months to discontinuation of methotrexate.Conclusions: Methotrexate appeared to be an effective and safe therapy for en coup de sabre patients.

Efficacy and tolerance of methotrexate in maintenance of remission in 49 patients with Crohn′s disease

Objective To analyze the efficacy and tolerance of methotrexate(MTX) in remission maintenance of Crohn′s disease (CD). Methods From June 2012 to August 2015, 49 CD patients who received MTX as mainly treatment medication to maintain remission were enrolled. The pre-medication history, efficacy, dosage and side effects of MTX were analyzed. The effects of inducing strategy on disease recurrence were analyzed. Chi-square test and t test were used for statistical analysis. Results Among the 49 patients, 34 (69.4%) received steroids for remission inducing, nine (18.4%) received infliximab for remission inducing and six (12.2%) achieved remission after operation. In the 44 patients treated with azathioprine (AZA) before, the median treatment time was one month and the dosage for withdrawal of AZA was (42.0±14.8) mg/d. The most common reason was leucopenia (81.8%, 36/44). Till the time point of follow-up, 46 of the 49 CD patients still took MTX orally with a median treatment time of 16 months, and the weekly dosage was (12.7±2.0) mg. Thirty-one cases (67.4%) achieved clinical stability, while 15 cases (32.6%) underwent clinical recurrence. The median Crohn′s disease activity index (CDAI) was 123.5±66.6. The weekly dosage of clinical stability group was (12.5±2.1) mg, and that of clinical recurrence group was (13.0±1.7) mg, there was no statistically significant difference between the two groups (t=0.802, P=0.426). The recurrence rate of steroids-induced remission group was 41.2% (14/34), which was higher than that of infliximab and surgery-induced remission group (1/15), and the differnce was statistically significant (χ2 =5.177, P=0.023). The common side effects were gastrointestinal reaction (26.5%, 13/49), impaired liver function (20.4%, 10/49) and leukopenia (12.2%, 6/49). Only three cases could not tolerate the side effects and underwent medication withdrawal. Conclusions As a second-line immunosuppressant for maintanence remission in CD, MTX is effective and well-tolerated in patients. So it can be an important option during the long course of CD. Key words: Methotrexate; Crohn disease; Maintenance of remission; Efficacy; Tolerability

Methotrexate is effective for the treatment of neuromyelitis optica spectrum disorders in Asian patients

AbstractBackgroundImmunosuppression is effective in the secondary prevention of neuromyelitis optica spectrum disorder (NMOSD) relapse. However, some of the newer immunosuppressive agents are costly or unavailable in resource‐poor countries; older immunosuppressive agents might be just as effective. We aimed to evaluate the efficacy and tolerability of methotrexate in treating NMOSD in an Asian cohort.MethodsWe retrospectively reviewed all patients with NMOSD treated with methotrexate at the National Neuroscience Institute, Singapore, between 1992 and September 2012. We compared the annualized relapse rates and disability as measured by the Expanded Disability Status Scale before and after methotrexate treatment.ResultsEight of 180 patients with central nervous system demyelinating diseases fulfilled the inclusion criteria. At median follow up of 53 months (range 42–70 months), the median post‐treatment annualized relapse rate was significantly lower than the pretreatment rate (0.00 [range 0.00–3.09] vs 0.97 [range 0.08–10.14] relapses). The median Expanded Disability Status Scale remained stable (pretreatment 6.5 [range 3.0–8.0] vs post‐treatment 6.0 [range 2.0–8.0], P = 0.238); 75% of our cohort remained relapse‐free on treatment. None of our patients were intolerant of methotrexate.ConclusionsMethotrexate is well‐tolerated in our NMOSD patients, and appears to be effective in decreasing relapse rates and preventing disability progression. It is widely available and less costly than newer immunomodulatory agents. As such, it can be recommended as a therapeutic option for NMOSD in patients who fail first‐line therapy.

Methotrexate in the treatment of rheumatic disease

The paper reviews the literature on the use of methotrexate (MT) in rheumatoid arthritis (RA) and other rheumatic diseases. The efficacy and tolerability of MT are evaluated. The findings permit its consideration as the gold standard treatment for RA. The main adverse reactions of MT, which are given in the literature and have been observed by us for 28 years of its use in patients with RA, are described.