Oral methotrexate

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Patient’s experience with subcutaneous and oral methotrexate for the treatment of rheumatoid arthritis

Patient’s experience with subcutaneous and oral methotrexate for the treatment of rheumatoid arthritis

This study is among the few that assessed the frequency of patient symptoms and side effects associated with ini- tiation of SQ and oral methotrexate in a real-world set- ting. We found several significant differences in the frequency of several of these compared to biologic ther- apy. For example, between one-third and one-half of pa- tients receiving either formulation of MTX reported malaise and between half and three-quarters reported fa- tigue, a much greater proportion than in the biologic users (22 %). At least some hair loss was reported by ap- proximately 30 % of patients in both MTX arms. The patient-reported prevalence of diarrhea was lower among patients receiving SQ MTX than among those receiving oral MTX, although nausea was more frequent with SQ MTX. Rates of mental fog and hair loss also were highest among patients receiving SQ MTX, and the greater prevalence of these symptoms may possibly reflect higher drug levels. Both the incidence and the magnitude of injection pain associated with SQ MTX was significantly lower than that associated with etaner- cept and adalimumab.

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Review on oral methotrexate in medical management of ectopic pregnancy: a 2 years experience in hospital Shah Alam

Review on oral methotrexate in medical management of ectopic pregnancy: a 2 years experience in hospital Shah Alam

Results: 29 patients were successfully treated with oral methotrexate 60 mg (82.8%). Another 6 patients had to undergo laparoscopic surgery with confirmed leaking, ruptured tubal pregnancy. 4 patients needed second dose of Methotrexate due to rising HCG level and all of them were successfully treated after the second dose. The side effects of oral methotrexate were tolerated well by all patients. There are numbers of predictors for success which are the level of HCG <4000 iu/litre, size of mass <4cm, no abdominal pain during early presentation and decrease of HCG level in between day 4 to day 7 after oral methotrexate.

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A New Regimen in the Treatment of Psoriasis Using Oral Methotrexate

A New Regimen in the Treatment of Psoriasis Using Oral Methotrexate

Background: Methotrexate is a well-known standard therapy for psoriasis. The standard regimen is using six (2.5 mg) tablets/week that might be with many side effects. Objective: Finding a new regimen for oral methotrexate aiming to decrease side effects and increase its effectiveness. Patients and Methods: This therapeutic, comparative study done at the Center of Derma- tology, Medical city, from October 2017 to October 2018. Fifty-three patients with moderate to severe psoriasis completed the study. They were divided into: Group (A) (27) patients were treated with the new oral regimen and Group (B) (26) patients were treated with the six tablets/week. Investigations including CBC, LFT and RFT were done. PASI score, BSA and side effects especially gastrointestinal ones were recorded. Results: They were 29 males and 24 females. Age ranged from 18 - 67 years. Disease duration ranged from 1 - 30 years. BSA involved ranged from 20% - 79%. The PASI score ranged from 10.2 - 45.7. After 8 weeks of treatment, there was statistically significant difference (p-value > 0.001) regarding PASI score and gastrointestinal side effects being less in Group (A). Group A patients were more satisfied. Con- clusion: The new regimen used in the present study has lower gastrointestin- al side effects and more efficacy.

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COMPARATIVE STUDY OF ORAL METHOTREXATE, NARROW-BANDULTAVIOLET-B AND COMBINATION OF BOTH ORAL METHOTREXATE AND NARROW-BAND ULTRAVIOLET-B IN CHRONIC PLAQUE PSORIASIS

COMPARATIVE STUDY OF ORAL METHOTREXATE, NARROW-BANDULTAVIOLET-B AND COMBINATION OF BOTH ORAL METHOTREXATE AND NARROW-BAND ULTRAVIOLET-B IN CHRONIC PLAQUE PSORIASIS

Ninety patients were consecutively selected and allocated into three groups, thirtyeach Viz group A. B and C. Exhibited to Oral methotrexate, NBUVB, combination of both Oral methotrexate and NBUVB. In group A, initial dose of 7.5 mg per week was given in 3 equal devided doses spaced at 12 hours apart and dose was gradually increased by 2.5 mg/week to a maximum of 15 mg/week, till PASI achieves 75 or for 12weeks whichever was first. Liver biopsy was not done in these cases, because of normal liver chemistry, history and physical examination and the total cumulative dose of 1.5 gm was not given in these cases.

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The Efficacy of Subcutaneous Versus Oral Methotrexate in Patients with Juvenile Idiopathic Arthritis

The Efficacy of Subcutaneous Versus Oral Methotrexate in Patients with Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood and is a significant cause of both short and long term disability 1 . The aim of modern treatment of JIA is rapid induction of disease control to prevent joint damage, to maximize physical function and to achieve a normal lifestyle 2 . Medications that slow the progression of Rheumatoid arthritis are called disease modifying anti Rheumatic drugs (DMARDs). American College of Rheumatology (ACR) recommends early use of DMARDs, so that they can slow or help inhibition of joint damage. Commonly used DMARD s are: methotrexate (MTX), sulfasalazine, hydroxychloroquine, leflunomide and cyclosporine. Over the years of clinical use, methotrexate has transformed the outlook of children

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Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study

Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study

Our cohort of patients with IP had a 2- and 5-year probability of remaining on MTX of 82% and 72%, respectively. For those who satisfied the 2010 ACR/ EULAR RA classification criteria the 2- and 5-year probability of remaining on MTX was higher at 85% and 77%, respectively. This is higher compared to previous studies of oral and subcutaneous (SC) MTX [8, 14, 15]. Mata et al. reported a 5-year MTX sur- vival of 45% in a cohort of 152 Spanish patients with RA. However, their cohort was recruited pre-2000 and included patients who had failed previous DMARD therapy. Edwards et al. studied participants from the UK General Practice Research Database pre- scribed MTX for any indication and reported a 57.1% 5-year probability of MTX persistence. Müller et al. investigated the persistence to SC MTX in patients who were DMARD- naïve and demonstrated much lower rates of persistence with only 53% remaining on SC MTX monotherapy at 2 years. The higher MTX persistence seen in the NOAR cohort may therefore be due to a more homogenous cohort of patients starting oral MTX as their first DMARD early within their disease onset. Toxicity remains a concern for patients commencing MTX therapy and high levels of concern are associated with reduced ad- herence to MTX [16]. In our cohort, 16% of partici- pants stopped MTX due to an adverse event. This is in concordance with previous results reported in the literature [17, 18]. Twenty per cent of patients stopped MTX because of a reported adverse event which could have been identified by routine blood test monitoring. Gastrointestinal side effects were the most frequent self-reported cause of MTX failure due to an adverse event.

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Though Methotrixate has a well-recognized side-effect of acute hypersensitivity pneumonitis in approximately 5% of patients, some authors have questioned whether this pulmonary toxicity is actually a reflection of progressive lung injury due to RA [30-32], but in our study there is no clinico-radiological evidence of pulmonary affection in patients who received methotrixate. A prospective study in UK, regarding chronic pulmonary effects of low-dose oral methotrexate in patients with RA by Dawson JK et al., found no evidence to suggest from clinical, HRCT assessment or serial pulmonary function tests that low-dose methotrexate is associated with chronic interstitial lung disease, thus supporting the finding in our study [31]. Similarly, Rojas-Serrano J et al., in their study also found that methotrixate is not negatively influencing the outcome of treatment in RA patients [33].

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Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

Notes: Significant improvement in disease control was observed following transition from oral to subcutaneous MTX (40 patients were switched because of inadequate efficacy; 63 were switched because of gastrointestinal side effects). Republished with permission of John Wiley and Sons Inc., from Hameed B, Jones H. Subcutaneous methotrexate is well tolerated and superior to oral methotrexate in the treatment of rheumatoid arthritis. Int J Rheum Dis. 2010;13(4):e83–e84.© 2010 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd, permission conveyed through Copyright Clearance Center, Inc. 56

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Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

the effect of methotrexate. Therefore, the total effect from the combination of biologics and methotrexate will be greater. For example, for infliximab plus methotrexate, the effect is esti- mated as a standardized mean difference of 1.04 (0.36 + 0.68), which is a large effect. For most agents, the total benefit is high-moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis. It is worthwhile pointing out that the scores did not decrease, with only two exceptions (one trial of infliximab and one of etan- ercept), suggesting that these agents slow progression rather than stop it. The results were not statistically different between agents, although infliximab was superior to the bottom four agents in each table. This should be interpreted with caution

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Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: a biomarker study of MOBILITY

Sarilumab plus methotrexate suppresses circulating biomarkers of bone resorption and synovial damage in patients with rheumatoid arthritis and inadequate response to methotrexate: a biomarker study of MOBILITY

ACR: American College of Rheumatology; ANOVA: Analysis of variance; C1M: Collagen type I matrix metalloproteinase-cleaved fragment; C2M: Collagen type II matrix metalloproteinase-cleaved fragment; C3M: Collagen type III matrix metalloproteinase-cleaved fragment; CRP: C- reactive protein; CRPM: C-reactive protein matrix metalloproteinase-derived fragment; CTX-1: Collagen type I matrix metalloproteinase-cleaved fragment C-telopeptide 1; DAS28-CRP: 28-joint disease activity score by C-reactive protein; ELISA: Enzyme-linked immunosorbent assay; ES: erosion score; FLS: Fibroblast-like synoviocytes; IL-6: Interleukin 6; IL- 6R: Interleukin 6 receptor; JSN: Joint space narrowing; LDA: Low disease activity; MMP: Matrix metalloproteinase; mTSS: van der Heijde modified total Sharp score; MTX: Methotrexate; MTX-IR: Inadequate response to methotrexate; OC: Osteocalcin; OPG: Osteoprotegerin; q2w: Every 2 weeks; RA: Rheumatoid arthritis; RANKL: Receptor activator of nuclear factor-kB ligand; sRANKL: Soluble receptor activator of nuclear factor-kB ligand; TNF: Tumor necrosis factor

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High Dose Methotrexate and Leucovorin Rescue Therapy in Childhood Malignancies: Experience in Resource-Limited Country

High Dose Methotrexate and Leucovorin Rescue Therapy in Childhood Malignancies: Experience in Resource-Limited Country

Results: We evaluated and compared toxicity of repeated courses of high dose methotrexate (HDMTX) in five groups of pediatric patients. Neutropenia was observed in 83.3% case and vomiting in 70% during chemotherapy. Diarrhoea 12.5%, oral mucositis in 56.20% patients were noted. Low hemoglobin level, was observed in 14.58%, thrombocytopenia in 20.80% patients. Vomiting and diarrhea was most frequent in cycle 2>1>3>4, whereas mucositis, fever was most frequent in Cycle 1>2>3>4 and raised serum transaminase in cycle 3>2>1>4. Two patients had <100 creatinine clearance. There was significant relationship between neutropenia with toxicities like vomiting and mucositis (p<0.05).

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Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature

Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature

Medical treatment began with 2 courses of pulsed IVMP 1 g over 3 days, followed by daily oral prednisol- one, initially at 2 mg/kg, and methotrexate 15 mg/m2. At week 2 she had her first dose of cyclophosphamide 500 mg/m2, monthly dosing for 5 doses, together with IVIG at 1 g/kg initially at fortnightly dosing. Her cyclo- phosphamide dose was decreased to 375 mg/m2 after 2 doses due to microscopic haematuria. Muscle strength began to improve but regressed again after a period of reduced access to physiotherapy due to chickenpox con- tact. Her medical treatment was subsequently escalated and, at week 16, she received her first dose of rituximab,

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Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone

Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone

These post hoc analyses of the DE019, PREMIER and OPTIMA studies found that significantly higher rates of CDC were observed following 1 year of treatment with Figure 3 Frequency of responders to each CDC criterion (SDAI≤3.3, HAQ-DI<0.5 and ΔmTSS≤0.5) at week 52 based on study treatments (A) DE019, ADA+MTX; (B) DE019, PBO+MTX; (C) PREMIER, ADA+MTX; (D) PREMIER, PBO+MTX; and (E) OPTIMA, open-label ADA+MTX (Rescue ADA arm). ADA, adalimumab; CDC, comprehensive disease control; HAQ-DI, Health Assessment Questionnaire Disability Index; IR, inadequate response; ΔmTSS, change in modified total Sharp score; MTX, methotrexate; PBO, placebo; SDAI, Simplified Disease Activity Index.

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Methotrexate-associated lymphoproliferative disorder in the stomach and duodenum: a case report

Methotrexate-associated lymphoproliferative disorder in the stomach and duodenum: a case report

Background: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) can present as a benign lymphoid proliferation or a malignant lymphoma in patients taking MTX. Almost 50% of MTX-LPD cases show spontaneous remission after withdrawal of MTX treatment. Studies have suggested that the hyper-immune state of rheumatoid arthritis, the immunosuppressive state associated with MTX, and the carcinogenicity of the Epstein-Barr virus might contribute to MTX-LPD development. Although most cases of MTX-LPD occur at extranodal sites, few cases of MTX- LPD affecting the stomach and duodenum have been reported. To our knowledge, no other study has reported on the endoscopic observations of dramatic withdrawal and appearance of multiple digestive tract lesions in a short period of time. Herein, we report the clinical course and imaging findings of our case, which may be useful for understanding the pathological condition of MTX-LPD.

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Turkish Compliance and Adaptation of EULAR 2013 Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: Expert Opinion of TLAR

Turkish Compliance and Adaptation of EULAR 2013 Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: Expert Opinion of TLAR

for classification of DMARDs so that they are now divided into two main classes: synthetic (sDMARDs) and biological DMARDs (bDMARDs). Synthetic DMARDs are then divided into two groups as conventional synthetic (csDMARD) and targeted synthetic (tsDMARD) DMARDs. Conventional sDMARDs comprise methotrexate (MTX), sulfasalazine and leflunomide. Tofacitinib is a newly developed synthetic DMARD which targets janus kinases, thus it is called as tsDMARD. Tumor necrosis factor (TNF) inhibitors [infliximab (IFX), etanercept (ETN), adalimumab (ADA), golimumab, and certolizumab pegol], abatacept (inhibitor of T cell costimulation), rituximab (the monoclonal antibody against CD20 of B cells), tocilizumab (TCZ) [monoclonal antibody of the interleukin 6 (IL-6) receptor], and anakinra (IL-1 inhibitor) are known as biologic originator (bo) molecules. Biosimilars are named as bsDMARDs (eg: bs-IFX). 2

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Management of tubal ectopic pregnancy in a tertiary care health center

Management of tubal ectopic pregnancy in a tertiary care health center

The woman was referred for surgical treatment in cases of tubal rupture and in patients whose serum β-hCG levels decreased by ≤15% or a plateau was reached without any decrease after two repeat doses of methotrexate. Patients not fit for medical management were managed surgically either by laparoscopy or by laparotomy. Follow up was done by sonography in both expectant and medical management modalities.

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In vitro inhibition of HUVECs by low dose methotrexate – insights into oral adverse events

In vitro inhibition of HUVECs by low dose methotrexate – insights into oral adverse events

key pattern in RA therapy as recommended [6]. Since more than two decades, low dose methotrexate (MTX, 5-25 mg/weekly) has been established as first-line thera- peutic agent [7] and has thus been widely used drug in RA therapy [8]. Currently, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have recommended even higher dosages [9,10]. Previous to low dose therapy in RA, MTX was used in oncology at higher dose as antineoplastic agent [11]. Most of our knowledge about mechanism of action, pharmacokinetics and side effects of MTX is derived from high dose therapy, whereas the precise mechanism of antirheumatic action has not yet been un- derstood in detail [12]. MTX and its metabolites (MTX glutaminated) inhibit the dihydrofolate reductase (DHFR), thymidylat synthase and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, which leads to accumulation of extracellular adenosine. This extracellular

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Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis

Clinical utility of the oral JAK inhibitor tofacitinib in the treatment of rheumatoid arthritis

with psoriasis; the effectiveness and safety of tofacitinib was tested in another Phase IIB, randomized, double-blind, placebo-controlled study conducted among patients with moderate-to-severe psoriasis. By considering this chronic, inflammatory skin disease with a significant impact on health- related quality of life, three tofacitinib dosage regimens and placebo were compared to characterize the efficacy and safety of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis. A total of 197 patients were randomized to tofacitinib 2 mg, 5 mg, 15 mg twice daily, or placebo for 12 weeks. Six different patient-reported outcome (PRO) ques- tionnaires were completed during the study. Treatment with tofacitinib resulted in significant, dose-dependent improve- ments in several PROs versus placebo from week 2 onwards. At week 12, the least squares mean change from baseline for the Dermatology Life Quality Index, Itch Severity Score, and Short Form-36 questionnaire version 2, mental component scores were significantly greater for all active drug arms versus placebo (P,0.05), and significantly greater for tofacitinib 5 mg and 15 mg for the Short Form-36 physical component scores versus placebo (P,0.05). At week 12, all dose groups had significantly greater numbers of patients reporting “Clear” or “Almost clear” on the Patient Global Assessment of psoria- sis versus placebo. Finally, in patients with moderate-to-severe chronic plaque psoriasis, short-term (12-week) treatment with oral twice-daily tofacitinib improved health-related quality of life outcomes and patient assessments of disease severity and symptoms, with an early onset of efficacy. 27

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Safety and efficacy of methotrexate in psoriasis : a meta analysis of published trials

Safety and efficacy of methotrexate in psoriasis : a meta analysis of published trials

Few would argue that methotrexate is as effective as modern biologics for the treatment of moderate to severe psoriasis. Its comparative inferiority has previously been summarised in an in-depth meta-analysis [1]. However, when trying to determine just how effective it is, or just how common side effects occur, we are confronted with a limited database. In terms of safety, the present analysis uncovers a systematic bias toward under-reporting of adverse effects in studies of small sample size (S4 File). This observation adds support to our inclusion of studies using the same dose range as used for psoriasis in similar indications (i.e. chronic inflamma- tory, non-cancer indications). If one were to restrict safety analysis to studies on psoriasis, many of the adverse effects clinically relevant for psoriasis patients simply would not be detect- able due to limiting cohort sizes. Moreover, one inherent overall limitation is the duration of published studies. In general, these are too short to detect delayed-onset adverse effects. Thus, only real-world data would be able to identify frequencies of late-onset adverse effects occur- ring with long-term dosing.

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Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score

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