Side Effects Of Methotrexate Research Articles

A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology.

Methotrexate (MTX) is a folate analog widely used against a range of diseases including malignancies and autoimmune disorders. Its high effectiveness-price ratio also won extensive application in ophthalmology. On the other hand, although MTX has an excellent pharmacological efficacy, MTX associated side effects in clinical use, which vary from patient to patient, are nonnegligible. There is no comparatively systematic review on MTX associated side effects and its risk factors. This review aimed to reveal novel clinical approaches of MTX and its adverse effects in order to provide a reference for ophthalmic scholars in clinical application of MTX.

SAT0150 CHANGES IN PATIENT-REPORTED OUTCOME (PRO) SCORES FOR NAUSEA AND FATIGUE FOLLOWING WEEKLY METHOTREXATE DOSE IN A REAL-WORLD SAMPLE OF RA AND PSA PATIENTS IN THE ARTHRITISPOWER REGISTRY

Background:Methotrexate (MTX) is frequently used in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) because of its beneficial effects in both populations1-3. Despite the well-known benefits of MTX, it is associated with a number of potential side effects4-6These include nausea and fatigue, are often temporally related to the timing of weekly MTX administration, and can be severe. The combined patient-reported side effects, along with potential of long-term toxicity, may make use of MTX more burdensome. Currently, there is a gap in patient-centered studies that focus on patients’ experience with MTX.Objectives:Examine patient temporal experience of fatigue and nausea relating to oral MTX therapy for the treatment of RA and PsA.Methods:Adult US patients in the ArthritisPower registry with self-reported RA or PsA taking MTX for less than 10 years were invited to participate in the study via email invitation. Participants (pts) completed a screener and brief online survey. In an ancillary study to the ArthritisPower registry and using a self-controlled case series study design where pts serve as their own control to avoid between-person confounding, pts were asked to complete a set of up to 8 assessments within 6-36 hours (‘risk’) and 96-144 hours (‘control’) after taking their oral dose of MTX each week, for up to 4 weeks. Risk and control windows were selected based on the expected temporal relationship between MTX use and peak onset of these symptoms. Assessments included PROMIS short forms for same-day Fatigue, same-day Nausea/Vomiting, and Patient Global. Descriptive statistics were conducted using paired t-tests two-way comparisons. Within-person change in PROMIS scores between the risk (1-2 days after MTX) and control (4-6 days after MTX) windows were analyzed using mixed models for repeated measures, stratified on whether pts reported fatigue or nausea with MTX at baseline. Recruitment for this study is ongoing.Results:As of December 2019, 91 pts had participated, of whom 76.9% were living with RA and 28.6% with PsA, with mean baseline PROMIS Patient Global score (SD) of 39.5 (7.1). Mean age (SD) was 50.9 (12.0) years, 84.6% female, 92.3% White, with mean BMI 33.7 (8.8). Mean duration of MTX treatment among current users was 2.1 (2.8) years. Among pts, 41.8% were on a biologic DMARD and 58.2% on non-biologic DMARDs only. Among pts reporting baseline nausea (n=30, 33.0%) where paired within-week measures were observed (n=64 observations among 20 pts), the mean increase in the PROMIS Nausea score was 4.5 units (adjusted p=0.003). Among those reporting MTX-associated fatigue (n=39, 42.9%) as a side effect of MTX on their baseline survey where paired within-week measures were observed (n=96 observations among 28 pts), the mean increase in PROMIS Fatigue was 4.7 (adjusted p=0.004) units. In those pts, the proportion of pts with worsened nausea and fatigue with minimally important difference of >5 units7-8was 40.0% (nausea), and 60.7% (fatigue) [Figures 1 and 2].Conclusion:People taking MTX to manage RA or PsA commonly experience bothersome side effects, notably fatigue and nausea, that are temporally related to weekly MTX dosing. In this sample, one-third or more of pts were bothered by nausea or fatigue shortly after MTX dosing, many of them with clinically meaningful symptoms.

Ethanolic extract of Iris songarica rhizome attenuates methotrexate-induced liver and kidney damages in rats.

The long-term sequelae of methotrexate (MTX) remain the major cause of concern for both patients and therapists. Therefore, new approaches to decrease MTX side effects are needed. The study was carried out to evaluate the effects of Iris songarica Schrenk (IS) rhizome extract against MTX-induced hepatic and renal injuries in rats. Forty male Wistar rats were randomly divided into five groups (n=8) including control, MTX, IS50, IS150 and IS300. Control and MTX groups were only treated orally with saline; whereas, IS50, IS150 and IS300 groups were treated with IS extract at three different doses (50, 150, and 300 mg/kg, respectively). Besides, the MTX and experimental groups were received a single dose of MTX (20 mg/kg) intraperitoneally on day 4. On the ninth day, animals were sacrificed, blood transaminases, urea and creatinine were assessed and the concentration of malondialdehyde (MDA) and the activity of super-oxide dismutase (SOD) were determined in both liver and kidney tissues. Moreover, hepatic and renal damages were evaluated histopathologically. MTX by increasing oxidative stress (MDA) and decreasing antioxidant capacity (SOD) induced hepatic and renal damages as confirmed by biochemical and histological parameters analyses. However, treatment with IS caused significant improvements in hepatic and renal histological architectures and SOD activity (p<0.01) along with reducing liver enzymes, urea, creatinine and MDA (p<0.01). The results of the present study showed that IS extract through antioxidant and probably anti-inflammatory activities, could effectively limit MTX-induced hepatic and renal injuries in rats.

Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats

Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.

Replacing Methotrexate with Letrozole in Cases of Early Ectopic Pregnancy as an Innovative Therapy - A Short Communication

In cases of early ectopic pregnancy the only medical therapy advocated till now has been single or multiple dose methotrexates with some preconditions. Here the role of an aromatase inhibitor, letrozole is discussed as a novel drug that possibly can be considered for replacement of methotrexate in view of its simplicity of use, cheap, relatively free of side effects associated with methotrexate, not having many contraindications other than the haemodynamic stability, size of mass, ruptured ectopic pregnancy. Currently letrozole is being utilized commonly for the treatment of hormone sensitive breast cancer, besides as a drug for ovulation induction in cases of poly cystic ovarian syndrome (PCOS). Only more randomized controlled trials (RCTs) are needed before one can safely utilize it in routine clinical practice without fear of any haematological side effects of methotrexate.

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes.

Rheumatoid arthritis (RA), a common inflammatory disorder of the joints characterized by synovitis and pannus formation, often results in irreversible joint erosion and disability. Methotrexate (MTX) is the first-line drug against RA, but the therapeutic effects are sub-optimal due to its poor retention at the target sites and systemic side effects. Multifunctional nanoparticles are highly promising agents for minimally invasive, traceable and effective targeted therapy.Methods: This study developed iRGD peptide-functionalized echogenic liposomes (iELPs) which encapsulates MTX and indocyanine green (ICG) fluorescent probe through the thin film-hydration method.Results: The resulting iELPs showed high affinity for endothelial cells overexpressing αvβ3 integrin, favorable acoustic response and fluorescence tracking properties. Also, near-infrared (NIR) fluorescence imaging of iELPs and ultrasound-triggered drug release of MTX were proved in a mouse RA model, greatly improving the therapeutic efficacy and reducing MTX side effects. Histological assessment of the articular tissues further revealed significantly lower inflammatory cell infiltration and angiogenesis in the iELPs-treated and sonicated mice.Conclusion: Our study provides a promising nanoplatform for integrating ultrasound-controlled drug release and NIR fluorescence imaging for RA treatment.

Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?

Nitrous oxide (N2 O) is frequently used for short anesthesia/analgesia in children undergoing painful or repetitive procedures. Children with acute lymphoblastic leukemia (ALL) require repeated lumbar punctures with direct instillation of intrathecal chemotherapy, usually the anti-folate agent methotrexate, during their treatment. These procedures are frequently performed under anesthesia. Concerns have been intermittently raised about a drug interaction between methotrexate and N2 O that may potentiate the undesirable side effects of methotrexate, including neurotoxicity. However, the clinical evidence consists mainly of isolated case reports leading to a lack of consensus among pediatric anesthetists about the relative risk benefits of using N2 O in children with ALL. In this article, we review the biochemical basis and scientific observations that suggest a significant interaction between N2 O and methotrexate due to their dual inhibition of the key enzyme methionine synthase. The possible role of this interaction in potentiating neurotoxicity in children with cancer is discussed, and arguments and counterarguments about the clinical significance of this largely theoretical relationship are explored. Following comprehensive review of all the available data, we make the case for the circumstantial evidence being sufficiently compelling to prompt a review of practice by pediatric anesthetists and call for a precautionary approach by avoiding the use of N2 O in children receiving concurrent methotrexate.

Immunomodulatory Effect of Carica Papaya and Actinidia Delicosa on Methotrexate Induced Immunosuppression in Male Rats

This study was carried out to explore the effects of alcoholic extract of Carica papaya fruit (C. papya) and Actinidia delicosa (Kiwi) fruit on some immunological, proinflammatory and anti-inflammatory biomarkers in methotrexate (MTX) treated rats. Forty adult male rats were weighted (130-160gm) and equally allocated into four groups and treated daily for 8weeks with orally as follow: Group G1: (control group) received tap water, G2: rats in this group were injected (20mg/kg /B.W) of MTX in 5thweek, G3: were orally received daily (400 mg/kg /B.W) of Carica papaya fruit alcoholic extract and injected (20mg/kg /B.W) of MTX in 5thweek , G4: were orally received daily (400mg/kg /B.W) of Actinidia delicosa fruit alcoholic extract and were injected (20mg/kg /B.W) of MTX in 5thweek. At the end of experiment, all animals were sacrificed and blood was drawn from median canthus of eye for measuring Serum immunoglobulin M, Serum immunoglobulin G, TNFα, interleukin-10 and C – reactive protein concentrations. Liver tissue collected in liquid nitrogen for Real Time PCR of IL1β and IL6 mRNA expression levels. Spleen tissue collected for histopathological examination and immunohistochemistry of TNFα expression levels. The results of the current study revealed A significant increase in serum serum IgM, IgG and IL10 as well as significant decrease in serum CRP concentrations and TNFα concentrations , mRNA expression levels of IL1β IL6 and immunohistochemical expression of TNFα were return to normal following extract administration comparing to the immune-suppression effect of MTX. Histopathological examination of spleen proved the protective effect of C.papaya and Kiwi fruit extract against necrosis and degenerative changes caused by MTX injection. Immunohistochemically, the expression level of TNFα in spleen tissue was decreased in Carica papaya fruit and Actinidia delicosa fruit groups when compared to MTX treated group. Conclusion, alcoholic extract of Carica papaya fruit and Actinidia delicosa fruit compete the side effects of MTX correlated with immune suppressive and pro-inflammatory effect.

Biologics in the treatment of juvenile idiopathic arthritis : A comparison of mono- and combination therapy with synthetic DMARDs

In polyarticular juvenile idiopathic arthritis, methotrexate (MTX) is still used as first-line treatment. In case of insufficient response or intolerance, anumber of biologics are now available. This faces physicians with challenging choices. Biologics are often combined with MTX, although in JIA there is little evidence and inconsistent results from various studies. In rheumatoid arthritis, combination therapy with tumor necrosis factor (TNF) inhibitors has been associated with higher efficacy. Tocilizumab appears to be highly effective as amonotherapy. MTX has aprotective effect on the formation of anti-drug antibodies, which is particularly important for the use of anti-TNF antibodies. This could also be observed in children. For golimumab, combination with MTX is mandatory according to its approval, as is the cause for abatacept. With regard to tolerability, apart from the classic side effects of MTX, there are no other significant differences concerning the combination of MTX and biologics. In case of MTX intolerance, leflunomide may be considered as an (unapproved) alternative.

Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis

ObjectiveTo assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD). MethodsWe performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected. In structured workshops for discussion and assessment of each article, 6 could be meta-analyzed for the primary and secondary outcomes: achievement of American College of Rheumatology (ACR) 20 and its core set components; and change of serum C-reactive protein (CRP) levels, Health Assessment Questionnaire Disability Index (HAQ-Di), liver enzyme aspartate transaminase/alanine transaminase ratio, new gastrointestinal (GI) side effects and infections. ResultsA total of 1984 patients were included: 986 took leflunomide and 998 methotrexate. The probability of achieving ACR 20 had an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.74, 1.06) with a trend toward favoring methotrexate; reduction of the swollen joint count was greater for methotrexate: mean difference=0.82 (95%CI 0.24, 1.39); tender joint count, physician global assessment, HAQ-Di, and serum CRP levels revealed no significant difference between groups. Increased liver enzymes were more frequent in the leflunomide group, OR=0.38 (95%CI 0.27, 0.53), and new GI complaints were more common with methotrexate (OR=1.44; 95%CI 1.17, 1.79). There was no difference in the incidence of non-severe infections. ConclusionLeflunomide used as the first DMARD in RA seemed to be as efficacious as methotrexate; only the reduction of swollen joint count was more marked for methotrexate. Leflunomide was linked to a greater increase in liver enzymes, but there were fewer GI complaints.

Hesperidin Alleviates Methotrexate-Induced Memory Deficits via Hippocampal Neurogenesis in Adult Rats.

Methotrexate (MTX), a folic acid antagonist, is widely used in cancer treatment. However, treatment with MTX reduces hippocampal neurogenesis, leading to memory deficits. Hesperidin (Hsd) is a flavonoid glycoside that promotes anti-inflammation, acts as an antioxidant, and has neuroprotective properties. Consumption of Hsd enhances learning and memory. In the present study, we investigated the protective effects of Hsd against MTX-induced impairments of memory and neurogenesis; male Sprague Dawley rats were administered with a single dose of MTX (75 mg/kg) by intravenous (i.v.) injection on days 8 and 15 or Hsd (100 mg/kg) by oral gavage for 21 days. Memory was tested using novel object location (NOL) and novel object recognition (NOR) tasks. Immunofluorescence staining of Ki-67, bromodeoxyuridine (BrdU), and doublecortin (DCX) was performed to assess cell proliferation, survival, and immature neurons. The data showed that Hsd and MTX did not disable locomotor ability. The MTX animals exhibited memory deficits in both memory tests. There were significant decreases in the numbers of cell proliferation, survival, and immature neurons in the MTX animals. However, co-administration with MTX and Hsd alleviated memory loss and neurogenesis decline. These results revealed that Hsd could protect against MTX side effects in the animals in this study.

Protective Effects of Magnesium Glycyrrhizinate on Methotrexate-Induced Hepatotoxicity and Intestinal Toxicity May Be by Reducing COX-2.

Magnesium isoglycyrrhizinate (MgIG), which has been widely employed to treat chronic hepatitis, is synthesized from 18-β glycyrrhizic acid, a main component of traditional Chinese medicine Glycyrrhiza uralensis Fisch. Although the protective effects of MgIG on methotrexate (MTX)-induced liver toxicity have been well-documented, the underlying mechanism remains elusive. MTX was initially used to treat pediatric acute leukemia, and has been widely applied to psoriasis therapy. However, its clinical applications are limited due to hepatotoxicity and intestinal toxicity. Herein, prophylactic administration of MgIG (9 and 18 mg/kg/day) significantly reduced the levels of aspartate aminotransferase and alanine aminotransferase in the serum of rats receiving intravenous injection of MTX (20 mg/kg body weight). MgIG also attenuated MTX-induced hepatic fibrosis. Moreover, it better protected against MTX-induced hepatocyte apoptosis and decreased the serum level of malondialdehyde than reduced glutathione (80 mg/kg/day) did. Interestingly, MTX-induced cyclooxygenase-2 (COX-2) expression, intestinal permeability and inflammation were attenuated after MgIG administration. In addition, MgIG (9 and 18 mg/kg) reduced MTX-induced colocalization of zonula occludens-1 (ZO-1) and connexin 43 (Cx43) in intestinal villi. In conclusion, MgIG exerted beneficial effects on MTX-induced hepatotoxicity and intestinal damage, as a potentially eligible drug for alleviating the hepatic and intestinal side effects of MTX during chemotherapy.

Enoxaparin prevents fibrin accumulation in liver tissues and attenuates methotrexate-induced liver injury in rats.

Methotrexate (MTX) is a widely used drug for treatment of many malignant, rheumatic, and autoimmune diseases. However, hepatotoxicity remains one of the most serious side effects of MTX. The extrinsic coagulation pathway is activated after tissue injury through the release of tissue factor (TF) which activates a cascade of clotting factors including prothrombin and fibrinogen. Liver sinusoidal endothelial cells express endothelial nitric oxide synthase (eNOS) as a source for nitric oxide (NO) that serves as vasodilator and antithrombotic factor. In the current study, we tested the possible role of coagulation system activation in MTX-induced hepatotoxicity. Our results showed that single-dose administration of MTX significantly altered rat liver functions with concurrent turbulence in redox status. Immunofluorescence staining showed accumulation of fibrin in the periportal hepatocytes and downregulation of eNOS expression in hepatic endothelial and sinusoidal cells following MTX treatment. Moreover, MTX administration increased the expression of inducible nitric oxide synthase (iNOS) and NOSTRIN (eNOS traffic inducer) in the hepatic sinusoids. On the other hand, pre-treatment with enoxaparin rescued against MTX-induced liver injury with subsequent amelioration of liver redox status. Furthermore, it significantly prevented the effect of MTX on the expression of fibrin, iNOS, eNOS, and NOSTRIN. We concluded that liver tissue aggregation of the coagulation product, fibrin, may play a crucial role in the pathogenesis of MTX-induced liver injury.

Protective effects of Cornus mas fruit extract on methotrexate-induced alterations in mice testicular tissue: Evidences for histochemical and histomorphometrical changes in an animal model study.

Methotrexate (MTX) as a chemotherapeutic agent, has adverse effects on reproductive organs by enhancing oxidative stress. In this study, the protective effects of Cornus mas fruit extract (CMFE) against MTX side effects were evaluated. Forty-eight mature male NMRI mice were divided into six groups: group 1 (control) received 0.10 mL per day of normal saline intraperitoneally (IP), group 2 received MTX (20.00 mg kg-1 per week, IP), group 3 received MTX along with CMFE 250 mg kg-1 per day by oral gavage, group 4 received MTX along with CMFE 500 mg kg-1 per day by oral gavage, group 5 received MTX plus 1000 mg kg-1 per day of CMFE by oral gavage, and group 6 received 1000 mg kg-1 per day of CMFE extract, orally. All animals were treated for 35 consecutive days. Thickness of testicular capsule and germinal epithelium and diameter of seminiferous tubules were measured. Intra-cytoplasmic levels of carbohydrate, unsaturated fatty acid (UFA) and alkaline phosphatase were assessed. Serum level of testosterone and testicular total antioxidant capacity (TAC) were also evaluated. The results demonstrated that MTX administration caused morphometrical parameters except the thickness of testicular capsule were significantly different in comparison to control group and decreased cytoplasmic concentration of carbohydrate in the first three layers of germinal epithelium and increased the UFA levels. Contrarily, CMFE ameliorates the condition. Moreover, CMFE increased testosterone level and increased the MTX-reduced TAC level. In conclusion, it was revealed that CMFE decreased the cellular atrophy by controlling the energy substrate utilization based on lipids and carbohydrates via provoking the testicular antioxidant status.

Methotrexate and mucositis: A merry-go-round for oncologists

AbstractHigh-dose methotrexate is the backbone of various regimens for treating lymphoid malignancies. Mucositis is a well-known, dose-related side effect of methotrexate. Prophylactic measures such as folinic acid rescue are useful but do not prevent mucositis in all the cases. Once severe mucositis (WHO Grade IV) sets in, mortality is very high. The index case highlights the natural course of methotrexate-induced mucositis and the need for swift and preemptive intervention.

Hypereosinophilia as a Rare Side Effect of Methotrexate in a Patient with Erythrodermic Psoriasis: The First Case Report

Methotrexate (MTX) has been approved for the treatment of psoriasis and is considered to be effective and relatively safe. This drug was widely used for treatment of psoriasis in Vietnam for many years. Life-threatening MTX toxicity is rare but may rapidly develop when the drug is administered. In line with the interface dermatitis and a remarked eosinophilic infiltration in the cutaneous lesion, the diagnosis of hypereosinophilia as an adverse reaction in our patient was supported by the dramatic improvement of symptoms and decreased eosinophils after withdrawal of MTX. To the best of our knowledge, this is the first case that showed isolated hypereosinophilia as an adverse reaction of MTX in psoriasis treatment that may challenge in early recognition. Awareness and prompt recognition of this severe adverse reaction can result in life-saving discontinuation of MTX.

Efficacy of High-Dose Methotrexate in Pediatric Non-Infectious Uveitis

ABSTRACTPurpose: To analyze the efficacy of high dose (≥ 15mg/m2/week) methotrexate (MTX) versus low dose (<15mg/m2/week) MTX in relation to time to remission on medication.Methods: Retrospective observational cohort study of pediatric patients with auto-immune uveitis with or without underlying systemic disease treated with MTX at the University Medical Center Groningen (the Netherlands) between 1990 and 2014. Primary outcome was time to remission on medication, which was defined as an observable inactive disease in the affected eye for longer than 3 months without the use of systemic corticosteroids.Results: A total of 42 patients were included. Mean age at uveitis diagnosis was 6.5 years (range 1.7 – 14.4), and 22 (52.4%) patients were male. Bilateral disease was found in 33 patients. Most patients (n=25) had anterior uveitis. JIA was the underlying systemic disease in 21 patients. Overall, 28 (66.7%) patients reached remission on medication in (median) 22.5 months (IQR 10.4- 45). Time to remission on medication in the low dose group (median 35.2, IQR 20.5 – 72.1 months) was significantly longer than in the high dose group (median 16.6, IQR 7.8 – 22.5 months) (p= 0.01). No statistically significant differences in ocular complications, steroid-sparing effect, cumulative dosage and side effects of MTX were found between the high and low dose groups.Conclusion: In this retrospective study on pediatric auto-immune uveitis, high dose MTX was associated with a shorter time to remission on medication as compared to low dose MTX, while side effects were comparable in both groups.

Add-on Clarithromycin and Tacrolimus Treatment for Rheumatoid Arthritis

A 67-year-old woman suffering from rheumatoid arthritis (RA) presented with gradual exacerbation of arthralgia and/or articular swellings. She was diagnosed with RA at 62 years of age and successfully treated using methotrexate (MTX) in combination with loxonin (LOX). Three months after this treatment, cytopenia occurred as a side effect of MTX; therefore, MTX was stopped. Thereafter, RA had been largely controlled using salazosulfapyridine in combination with prednisolone and LOX for almost 4 years. On this visit, because RA became worse, clarithromycin (CAM) was added in expectation of its anti-inflammatory effects on RA. CAM treatment was effective for RA, to a certain extent; however, the RA activity was not sufficiently suppressed. In order to suppress the RA activity further, tacrolimus (TAC), an armament in the treatment for active RA in Japan, was added. Three months after initiating TAC treatment, the RA activity was considerably suppressed. This case shows that physicians should consider add-on CAM and TAC treatment when existing ant-rheumatic agents show little effects on RA.

The Influence of Race and Sex on the Side Effect Profile of Methotrexate in the Treatment of Uveitis

ABSTRACTPurpose: To detect any correlation between race and sex and the side effects of methotrexate in uveitis treatment.Methods: Retrospective review of patients seen at Northwestern Memorial Hospital between August 2012 and September 2014 with a history of MTX treatment for uveitis. Demographic, treatment, and side-effect data were collected for each patient.Results: Ninety-seven patients were included (25 males, 72 females). Twenty-eight patients reported African American race, 60 reported Caucasian race, and the remaining 9 reported Asian, Hispanic, or Arabic ethnicity. Males experienced more gastrointestinal upset than females (24% versus 13.8%). Caucasians had more gastrointestinal complaints (20% versus 8%) while African Americans developed more hair loss (14% versus 6.6%), although the numbers were too small to detect a statistical difference.Conclusion: While our sample was small, these findings suggest racial and gender disparities in the side effects experienced by patients treated with methotrexate. This information may be useful to clinicians counseling patients on risk profile.

Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis

To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.