-
1.
Brief Update on Dermatologic Uses of Methotrexate.
Shah, RA, Nwannunu, CE, Limmer, AL, Patel, RR, Mui, UN, Tyring, SK
Skin therapy letter. 2019;(6):5-8
Abstract
Methotrexate (MTX), an agent originally intended for anti-neoplastic use, has been successfully employed in the treatment of a variety of dermatologic conditions. In addition to its multiple clinical indications, variable dosing and modes of administration make it a viable option for patients of all ages and most comorbidities. MTX is a folate analog that antagonizes dihydrofolate reductase, thus inhibiting thymidylate synthesis and, ultimately, the production of pyrimidine. Depending on dosage, MTX can function as an anti-inflammatory agent, immunomodulator, or antimetabolite. Patients suffering from psoriasis have benefited from MTX in addition to those with atopic dermatitis, chronic urticaria, pemphigus vulgaris, bullous pemphigoid, cutaneous lupus erythematosus, cutaneous sarcoidosis, and mycosis fungoides. Although patients with these conditions can benefit from MTX treatment, the drug can cause adverse sequelae, including hematologic, pulmonary, gastrointestinal, and hepatic side effects. Therefore, the drug should be administered under careful physician supervision.
-
2.
Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting.
Ferrara, G, Mastrangelo, G, Barone, P, La Torre, F, Martino, S, Pappagallo, G, Ravelli, A, Taddio, A, Zulian, F, Cimaz, R, et al
Pediatric rheumatology online journal. 2018;(1):46
Abstract
BACKGROUND Conventional pharmacological therapies for the treatment of juvenile idiopathic arthritis (JIA) consist of non-biological, disease-modifying antirheumatic drugs, among which methotrexate (MTX) is the most commonly prescribed. However, there is a lack of consensus-based clinical and therapeutic recommendations for the use of MTX in the management of patients with JIA. Therefore, the Methotrexate Advice and RecommendAtions on Juvenile Idiopathic Arthritis (MARAJIA) Expert Meeting was convened to develop evidence-based recommendations for the use of MTX in the treatment of JIA. METHODS The preliminary executive committee identified a total of 9 key clinical issues according to the population, intervention, comparator, outcome (PICO) approach, and performed an evidence-based, systematic, literature review. During the subsequent Expert Meeting, the relevant evidence was assessed and graded, and 10 recommendations were made. RESULTS Recommendations relating to the efficacy, optimal dosing and route of administration and duration of treatment with MTX in JIA, and to the issue of folic acid supplementation to prevent MTX side effects, use of MTX in the treatment of chronic JIA-associated uveitis, combination treatment with biologic agents, and the use of vaccinations in patients with JIA were developed. The selected topics were considered to represent clinically important issues facing clinicians caring for patients with JIA. Evidence was insufficient to formulate recommendations for the use of biomarkers predictive of treatment response. CONCLUSIONS These consensus recommendations provide balanced and evidence-based recommendations designed to have broad value for physicians and healthcare clinicians involved in the clinical management of patients with JIA.
-
3.
A systemic review and meta-analysis of the clinical efficacy and safety of total glucosides of peony combined with methotrexate in rheumatoid arthritis.
Feng, ZT, Xu, J, He, GC, Cai, SJ, Li, J, Mei, ZG
Clinical rheumatology. 2018;(1):35-42
-
-
Free full text
-
Abstract
To assess the efficacy and safety of the combination of total glucoside of peony (TGP) and methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). Randomized controlled trial (RCT) data on the traditional Chinese active component TGP combined with MTX vs. MTX alone for the treatment of RA was collected by searching the Pubmed, Embase, Cochrane Library, CNKI, VIP Journals database, and Wanfang database up to February 2017. Study selection, data extraction, data synthesis, and data analyses were performed according to the Cochrane standards. A total of eight RCTs involving 522 participants were included in this meta-analysis. Compared with MTX alone, the use of TGP combined with MTX exhibited better therapeutic effects for the treatment of RA (P = 0.004). In addition, TGP combined with MTX caused a more significant decrease in erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC) (P < 0.00001). However, no significant differences were found in C-reactive protein (CRP) (P = 0.19), duration of morning stiffness (DMS) (P = 0.32), or tender joint count (TJC) (P = 0.23) between the two groups. In addition, adverse events were more frequently reported in the MTX monotherapy group than in the TGP and MTX combination group (P = 0.0007). Our study demonstrates that TGP combined with MTX is more effective than MTX alone for the treatment of RA. Nevertheless, the adverse effects of the combination of TGP and MTX need to be further assessed. Due to the poor methodological quality of included trials, well-designed, multi-center, and large-scale RCTs are necessary to draw a more definitive conclusion.
-
4.
Pharmacogenomics of Methotrexate: Current Status and Future Outlook.
Cao, M, Guo, M, Wu, DQ, Meng, L
Current drug metabolism. 2018;(14):1182-1187
Abstract
BACKGROUND Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients. OBJECTIVE The present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and points out future development directions of individualized MTX therapy. METHODS Details regarding the pharmacogenetics and pharmacogenomics of MTX are obtained from PubMed literatures. CONCLUSION The influences of single nucleotide polymorphisms (SNPs) in genes involved in MTX pathway are controversial. Many pharmacogenetic associations are disease specific and race specific. Present studies have almost limited to some certain ethnic groups and diseases. The data from these studies are not convincing enough to draw far-reaching conclusions about the applicability of MTX pharmacogenetics in clinical practice. Studies with large scale and multiple centers are needed in the future. MTX-PG inhibits folic metabolism through three mechanisms. TS, MTHFR and ATIC are the rate-limiting enzymes separately. The function of SNPs in these genes is often onesided. Works focusing on the analysis of polymorphism in MTX transporters should be more efficient and meaningful.
-
5.
Morphea and Eosinophilic Fasciitis: An Update.
Mertens, JS, Seyger, MMB, Thurlings, RM, Radstake, TRDJ, de Jong, EMGJ
American journal of clinical dermatology. 2017;(4):491-512
-
-
Free full text
-
Abstract
Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.
-
6.
[Nonadherence and ineffective methotrexate treatment of inflammatory arthritis].
Batko, B
Wiadomosci lekarskie (Warsaw, Poland : 1960). 2017;(4):812-819
Abstract
Failure to comply with treatment recommendations in chronic diseases, including inflammatory arthritis, is one of the main reasons why patients do not achieve health benefits. It is widely recognized that effective pharmacotherapy requires a conviction to undertake and continue. In case of methotrexate therapy failure, it is necessary to consider the possibility and cause for non adherence to treatment. In order to achieve chosen therapy goals, cooperation of patient and physician is essential. A review of medical literature brings up a necessity to consider the differences in understanding and definition of both compliance and adherence, and whether the failure in treatment is tied to pharmacology, or inadequate patient knowledge. Patient education should entail thorough understanding of therapy goals, the mainstay role of methotrexate in current strategies and the benefits of consistent treatment. Attention should be paid to the role of methotrexate polyglutamates in monitoring therapy effectiveness, and the choice between subcutaneous and oral administration. A joint consideration of the dosing regimen, convenient methods of administration and dispelling any doubts over adverse events are milestones that will translate into better adherence.
-
7.
[Management of systemic lupus erythematosus].
Aringer, M, Schneider, M
Der Internist. 2016;(11):1052-1059
Abstract
In the last few decades a number of small, often largely unrecognized steps have fundamentally changed the management of systemic lupus erythematosus (SLE). The current goal is to stop all disease activity without long-term use of more than 5 mg prednisolone per day. Remission, i.e. absence of activity in the SLE activity score of choice, is the defined target in the treat to target approach. The essential basic measures include life-long hydroxychloroquine as well as protection from sunlight (UV) and vitamin D substitution. Patients suffering from SLE need more vaccinations than the healthy population and control of risk factors for atherosclerosis is critical for long-term survival. Methotrexate is on par with azathioprine. If disease activity cannot be controlled in this way, belimumab is an approved therapeutic option. Cyclophosphamide is still used but only in life-threatening situations, such as lupus nephritis or central nervous system (CNS) vasculitis and in drastically reduced doses. Alternatively, off-label mycophenolate mofetil (MMF) can be used particularly for lupus nephritis and off-label rituximab in refractory disease courses. Numerous novel approaches are being tested in controlled trials and it is hoped that new drugs will be available for SLE patients within a few years.
-
8.
Low-Dose Methotrexate (LD-MTX) in Rheumatology Practice - A Most Widely Misunderstood Drug.
Malaviya, AN
Current rheumatology reviews. 2016;(3):168-176
Abstract
Methotrexate (MTX) was synthesised as a folate antagonist for use in treating childhood leukaemia in 1940s. Gubner and colleagues in 1953 used several log-order lower doses of MTX that mimicked the anti-inflammatory properties of cortisone. They used it successfully in treating rheumatoid arthritis (RA). Their work was however overlooked because the Nobel Prize winning drug cortisone held sway in those days. With increasing awareness of the adverse effects of cortisone, interest was rekindled in discovering 'steroid-sparing' drugs. Hoffmeister and Willkens used low-dose MTX (LD-MTX) in treating RA patients in 1960s with impressive results. Pivotal trials in 1984-5 established the efficacy and safety of LD-MTX in treating RA that gained FDA approval in 1988. LD-MTX at doses <25-30 mg weekly as mini-pulses, is presently the standard-of-care for the treatment of RA. Its toxicities and adverse effects are rarely if ever life-threatening. This is in contrast to the high-dose methotrexate (HD-MTX) for treating malignancies at doses that are several log-orders higher and usually cause serious toxicities. While LD-MTX acts mainly as an anti-inflammatory drug by increasing tissue adenosine levels besides other mechanisms, HD-MTX has anti-proliferative cytotoxic action with different toxicity profile and adverse effects. In practical terms LD-MTX and HD-MTX are 2 different therapeutic agents. However, in developing countries like India the stigma attached to MTX as a cytotoxic 'cancer drug' still persists and most non-rheumatologists fear its use in RA. This review aims to allay such anxiety attached to LD-MTX so that they start using it in appropriate doses for treating RA.
-
9.
Overview and guidelines of off-label use of methotrexate in ectopic pregnancy: report by CNGOF.
Marret, H, Fauconnier, A, Dubernard, G, Misme, H, Lagarce, L, Lesavre, M, Fernandez, H, Mimoun, C, Tourette, C, Curinier, S, et al
European journal of obstetrics, gynecology, and reproductive biology. 2016;:105-9
Abstract
Our objective is to describe off-label use of methotrexate in ectopic pregnancy treatment using evidence based medicine. The patient group includes all women with a pregnancy outside the usual endometrium, or of unknown location. Method used was a Medline search on ectopic pregnancy managed using methotrexate treatment; evidence synthesis was done based on this current literature analysis. Level of evidence (LE) were given according to the centre for evidence base medicine rules. Grade was proposed for guidelines but no recommendation was possible as misoprostol is off label use for all the indications studied. In the absence of any contraindication, the protocol recommended for medical treatment of ectopic pregnancy is a single intramuscular injection of methotrexate (MTX) at a dosage of 1mg/kg or 50mg/m(2) (Grade A). It can be repeated once at the same dose should the hCG concentration not fall sufficiently. Pretreatment laboratory results must include a complete blood count and kidney and liver function tests (in accordance with its marketing authorization). MTX is an alternative to conservative treatment such as laparoscopic salpingotomy for uncomplicated tubal pregnancy (Grade A) with pretreatment hCG levels≤5000IU/l (Grade B). Expectant management is preferred for hCG levels<1000IU/l or in the process of spontaneous decreasing (Grade B). Intramuscular MTX is also recommended after the failure of surgical salpingotomy (Grade C) or immediately after surgery, if monitoring is not possible. Except in special circumstances, a local insitu ultrasound-guided MTX injection is not recommended for unruptured tubal pregnancies (Grade B). In situ MTX is an option for treating cervical, interstitial, or cesarean-scar pregnancies (Grade C). In pregnancies of unknown location persisting more than 10days in an asymptomatic woman who has an hCG level>2000IU/l, routine MTX treatment is an option. MTX is not indicated for combination with treatments such as mifepristone or potassium.
-
10.
Drug resistance in inflammatory bowel diseases.
Moreau, J, Mas, E
Current opinion in pharmacology. 2015;:56-61
Abstract
The management of patients with moderate to severe inflammatory bowel diseases, that is, Crohn's disease and ulcerative colitis, remains challenging. In recent years, therapeutic goal evolved from clinical remission to mucosal healing and deep remission. In order to achieve remission, it is important to appropriately choose and use available drugs. Therefore, anti-TNFα treatment should be rapidly used for severe and at-risk patients, sometimes in association with thiopurines or methotrexate. The monitoring of through levels and antibodies to anti-TNFα is relevant to optimize the treatment and to reduce drug inefficacy. However, the development of new drugs is required to offer alternative tools to severe and refractory patients.