Methotrexate For Psoriasis Research Articles

Use of cyclosporine and methotrexate in psoriasis

Use of cyclosporine and methotrexate in psoriasis

Unlocking the role of the B7-H4 polymorphism in psoriasis: Insights into methotrexate treatment outcomes: A prospective cohort study.

B7-H4 is a recently discovered member of B7 family that negatively regulates T-cell immunity, specifically Th1 and Th17 cell responses. However, its role in the pathogenesis of psoriasis has yet to be determined. This study aims to investigate the effect of B7-H4 polymorphism on the efficacy of methotrexate (MTX) and its mechanism in psoriasis. Four single nucleotide polymorphisms of B7-H4 were genotyped in 310 psoriatic patients who received 12-week MTX. The protein expression of B7-H4 in platelets was characterized using immunofluorescence staining, confocal laser scanning microscopy, and flow cytometry techniques. We found that GG genotype carriers of B7-H4 rs1935780 had a lower Psoriasis Area and Severity Index (PASI) 75 response rate and higher weight (p = 0.0245) and body mass index (p = 0.0185) than AA and AG genotype carriers. Multiple regression analysis showed that the PASI score at baseline (p = 0.01) and age at disease onset (p = 0.003) were positively correlated with PASI 75 response rate, while weight (p = 0.005) and the rs1935780 genotype (p = 0.003) were negatively associated with PASI 75 response rate. B7-H4 was expressed in the platelet plasma membrane and cytoplasm. Furthermore, the expression of B7-H4 protein in platelets was lower in good responders than in non-responders and was upregulated considerably after 12-week MTX or in vitro MTX stimulation in good responders. Collectively, these results demonstrate that psoriatic patients with GG genotype of B7-H4 rs1935780 had a poorer response to MTX. Low expression of B7-H4 protein in platelets correlated with better clinical outcomes of MTX in psoriasis.

Assessment of the Effect of Psoriasis and Methotrexate Treatment on Liver Stiffness by ARFI Imaging

Objective: To investigate whether psoriasis and methotrexate used in its treatment cause liver fibrosis and eventually to evaluate the safety of methotrexate in treatment.
 Method: 44 cases were included in the study. Methotrexate-using (group 1, n=14) and methotrexate-not-using (group 2, n=13) psoriasis patients were compared retrospectively with a healthy control group (group 3, n=17) according to mean shear wave rates obtained from sonoelastographic examinations with ARFI technique. 
 Results: Mean shear wave velocities were calculated as 2.57 ± 1.13 m/sec in the patients using methotrexate, 2.31 ± 1.16 m/sec in the patients who did not use methotrexate, and 1.56 ± 0.62 m/sec in the healthy control group. While the average shear wave velocity of the 3rd group was found to be significantly lower than that of the 1st and 2nd groups (p=0.032; p=0.012), no significant difference was observed between the 1st and 2nd groups (p=0.755).
 Conclusion: We think that the increase in liver tissue stiffness in patients using methotrexate for psoriasis is secondary to the inflammatory process caused by psoriasis itself rather than methotrexate, and methotrexate is safe for the liver in treatment.

Association of the characteristics of the blood metabolome and gut microbiome with the outcome of methotrexate therapy in psoriasis

Metabolic status and gut microecology are implicated in psoriasis. Methotrexate (MTX) is usually the first-line treatment for this disease. However, the relationship between MTX and host metabolic status and the gut microbiota is unclear. This study aimed to characterize the features of blood metabolome and gut microbiome in patients with psoriasis after treatment with MTX. Serum and stool samples were collected from 15 patients with psoriasis. Untargeted liquid chromatography–mass spectrometry and metagenomics sequencing were applied to profile the blood metabolome and gut microbiome, respectively. We found that the response to MTX varied according to metabolomic and metagenomic features at baseline; for example, patients who had high levels of serum nutrient molecular and more enriched gut microbiota had a poor response. After 16 weeks of MTX, we observed a reduction in microbial activity pathways, and patients with a good response showed more microbial activity and less biosynthesis of serum fatty acid. We also found an association between the serum metabolome and the gut microbiome before intervention with MTX. Carbohydrate metabolism, transporter systems, and protein synthesis within microbes were associated with host metabolic clusters of lipids, benzenoids, and organic acids. These findings suggest that the metabolic status of the blood and the gut microbiome is involved in the effectiveness of MTX in psoriasis, and that inhibition of symbiotic intestinal microbiota may be one of the mechanisms of action of MTX. Prospective studies in larger sample sizes are needed to confirm these findings.

Lymphangioma of the gallbladder

A 47-year-old woman, who was taking methotrexate for psoriasis, underwent routine liver function tests (LFTs) as part of her dermatology follow-up. It was noted that she had deranged LFTs, with an alanine transaminase of 124 and aspartate transaminase of 68, but normal inflammatory markers.

MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate in Psoriasis

AimsTo assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population.MethodsThis prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed.ResultsThe rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04).ConclusionsThis study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation.

Drug survival and predictor factors for discontinuation of methotrexate in psoriasis: a real-life multicenter study.

Drug survival is useful to evaluate long-term drug performance in daily practice. The aim of this study was to evaluate drug survival for methotrexate (MTX) monotherapy in patients with plaque-type psoriasis. We reviewed 3,512 follow-up charts of patients with psoriasis at five tertiary referral centers between January 2012 and January 2020. We analyzed baseline data and treatment outcomes of patients under MTX monotherapy. Drug survival was analyzed using Kaplan-Meier and Cox regression analyses. Patients with psoriasis who were treated with MTX monotherapy were enrolled (N=649). The median duration of drug survival was 15months (95% CI: 13.2-16.8). The overall drug survival rate was 54.7%, 17.4%, and 8% after 1, 3, and 5years, respectively. The main reasons for discontinuation were adverse effects (n=209, 32.2%) and inefficacy (n=105, 15.6%). Based on multivariate Cox regression analysis, the presence of nausea/vomiting (HR: 2.01, 95% CI: 1.49-2.71; P<0.001) was observed as a statistically significant risk factor for drug discontinuation. Age over 50years (HR: 0.68, 95% CI: 0.48-0.97; P=0.03) and using MTX dose ≥15mg/weekly were positive predictors for drug survival (HR: 0.72, 95% CI: 0.54-0.95; P=0.02). The average drug survival of MTX was 15months. MTX is still the first-line treatment of moderate-to-severe plaque psoriasis, as highlighted in guidelines. To prevent premature discontinuation, physicians need to look at the response time of at least 16-24weeks, especially when a stepwise dose increment is used. The presence of nausea/vomiting seemed to be associated with an approximately twofold risk of discontinuation.

Patch Testing During Immunosuppressive Therapy: A Systematic Review.

Patch testing, used in the assessment of allergic contact dermatitis, is ideally avoided in patients receiving immunosuppressive therapy because of concerns with reductions in accuracy; however, this is not well characterized in the literature. This systematic review summarizes patch testing results in patients receiving immunosuppressive therapy. We identified 16 studies, comprising 195 patients with dermatitis or psoriasis, who were patch tested while receiving immunosuppressants. Of these, 7 studies, comprising 85 patients with dermatitis, patch tests were performed before and during immunosuppression. Overall, 67.9% (n = 19) of the dermatitis patients receiving dupilumab maintained positive reactions to an allergen that previously graded as a 2+/3+ reaction. Several immunosuppressants were also associated with positive patch test results for various allergens. These include dupilumab, cyclosporine, and low-dose prednisone (≤10 mg/d) for dermatitis, and tumor necrosis factor α inhibitors, ustekinumab, and methotrexate for psoriasis. Ideally, it is preferable to patch test when patients are not receiving oral immunosuppressants or immunomodulators. However, clinicians may choose to assess the risks and benefits of patch testing for each patient given the impact of allergic contact dermatitis on patient quality of life.

16644 Utilizing Fibrosis-4 Score to assess risk for hepatic fibrosis in patients with psoriasis on methotrexate

Introduction: Methotrexate (MTX) is a valuable treatment for psoriasis. Guidelines recommend monitoring liver function tests (LFTs) every 1-3 months, although liver biopsy remains gold standard. Two novel tests, the Fibrosis-4 (Fib-4) score and Fibroscan, have been introduced to assess liver fibrosis noninvasively. This study highlights use of these tools in identifying patients treated with MTX for psoriasis at risk for hepatic fibrosis.

Methotrexate in Psoriasis and Psoriatic Arthritis.

Methotrexate (MTX) is the most commonly prescribed first-line therapy in psoriatic arthritis (PsA) internationally and is also commonly used in the treatment of psoriasis. However, data supporting its use in PsA are limited and significant toxicities can occur. This article summarizes a debate at the 2019 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting that focused on the use of MTX in psoriasis and PsA. Four clinicians and 1 patient research partner presented clinical study data and the patient experience summarizing the efficacy, tolerability, and toxicity of MTX for both skin and musculoskeletal manifestations. A survey of attending GRAPPA members collected data on current and planned future use of MTX across the world.

Topical methotrexate in dermatology: a review of the literature

Background Systemic methotrexate (MTX) is a useful treatment for many dermatologic conditions, however, the risk of adverse events prevents its use in patients with minimal or localized disease. Topical application of MTX may be an option to avoid the systemic adverse effects of oral MTX. Objective To assess what is known about the efficacy and safety of topical methotrexate. Methods A search on Pubmed was conducted. There were no limits on publication date. Results A total of 963 articles were discovered. Using our exclusion criteria, 916 articles were excluded; 47 articles were used for full text assessment. Topical MTX has been used primarily in psoriasis but also in mycosis fungoides, lymphomatoid papulosis, and oral precancerous lesions. Optimal delivery system and formulation for adequate penetration is still under investigation. Conclusion The quality of evidence for the utility of topical methotrexate in psoriasis is good, however, for other dermatologic diseases, the quality is poor. Topical MTX with improved delivery methods may be a viable tool against certain localized dermatologic conditions for patients who do not tolerate oral MTX. Further double-blinded randomized controled studies are needed to substantiate the utility of topical methotrexate.

Dermoscopy as a prognostic tool for the therapeutic response of phototherapy and methotrexate in psoriasis

Background Methotrexate and phototherapy are traditional treatments for psoriasis, but their prolonged use is associated with cumulative toxicity, so physicians are in a continuous need for tools to predict and monitor the progress of the disease.Objective To detect if there is any role for dermoscopy in determining the psoriatic patients’ response to phototherapy and methotrexate.Patients and methods A total of 70 patients with psoriasis were treated by methotrexate or phototherapy with narrow-band ultraviolet B for four months according to their local and general conditions. Psoriasis Area and Severity Index score calculation and dermoscopic examination were done at baseline, after 1 month, and after 4 months of starting treatment.Results A significant association was noted between changes in the vessel distribution in psoriatic lesions and the response to treatment according to Psoriasis Area and Severity Index score assessment along treatment visits, whereas presence of hemorrhagic dots was significantly associated with poor clinical response.Conclusion The use of dermoscopy in assessing vascular distribution and hemorrhagic dots may reflect the severity of psoriasis and can predict the clinical response to either methotrexate or phototherapy.

ORAL ULCERATIONS AS THE fiRST INDICATION OF FOLATE DEfiCIENCY SECONDARY TO METHOTREXATE THERAPY

Methotrexate is a commonly used drug for the treatment of psoriasis, arthritis, and many forms of cancer. Methotrexate inhibits cancer cells from multiplying and reduces inflammation in both psoriasis and rheumatoid arthritis. In cancer, methotrexate inhibits cells access to folate causing folate deficiencies in patients taking the drug. While the mechanism of action of methotrexate in psoriasis and rheumatoid arthritis is unknown, use in these conditions can also result in folate deficiency. We report a patient who was admitted to the hospital with painful oral and esophageal ulcers which ultimately was attributed to folate deficiency in the setting of methotrexate use. The patient was a 63-year-old male with RA who presented to the ED with a 3-week history of mouth and throat pain upon swallowing. He was unable to eat and reported a 12-pound weight loss. Intraoral exam revealed areas of erythema with diffuse ulcerations on the upper and lower left labial mucosa, soft palate and anterior maxillary gingiva. A CT scan of the head, neck, and brain, and upper EGD were all within normal limits. The presentation was consistent with vesiculobullous disease and we recommended ruling out a drug induced etiology. Upon evaluation of the patient's laboratory values, we found he had megaloblastic macrocytic anemia (red cell diameter 11.5-14.5), which is consistent with folate deficiency. The patient's folate level was measured at 6ng/ml. The normal reference range is 7.3-20 ng/ml. 6 is considered quite low. The patient was administered folic acid and methotrexate was discontinued temporarily. The patient's oral lesions resolved, and the patient was discharged. This case illustrates the importance of collaboration between the primary team and the oral healthcare professional as well as the recognition that while methotrexate can cause oral ulcers, in the setting of folate deficiency the severity of oral ulcers may be exacerbated.

Patient Diagnosed with Organizing Pneumonia after Using Methotrexate for Psoriasis

Patient Diagnosed with Organizing Pneumonia after Using Methotrexate for Psoriasis

Anti-psoriatic and toxicity evaluation of methotrexate loaded chitin nanogel in imiquimod induced mice model

Methotrexate loaded chitin nanogel (MCNG) was formulated for its topical use in psoriasis. MCNG was characterized by DLS, TEM and FTIR. The MCNG particles were spherical in shape with size of 196±14nm, having surface charge of +9.21±0.42 mv. MCNG exhibited greater swelling and drug release at acidic pH than neutral and alkaline conditions. The treatment with MCNG showed significant level of toxicity on HaCaT and THP-1 cells and was taken up well by HaCaT cells as revealed by fluorescent microscopy. MCNGs exhibited significant anti-inflammatory activity as revealed by the inhibitory effects observed on the activity of COX-2 and LOX-5 enzymes expressed in THP-1 cells. Skin permeation studies revealed an increased trasdermal flux of methotrexate from MCNG with loosened stratum corneum and other epidermal layers of skin in comparison with control methotrexate solution treated samples. Significant anti-psoriatic efficacy on imiquimod (IMQ) induced model of psoriasis without any dermal and systemic toxicities suggest that it as an ideal delivery platform for topical delivery of methotrexate in psoriasis. Thus it is expected to become a better alternative for the oral delivery of methotrexate in the selected disease.

Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis.

Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis. Of the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression. We observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment. Our results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.

Drug Utilization Evaluation of Methotrexate in Psoriasis in a Tertiary Care Teaching Hospital

Drug Utilization Evaluation of Methotrexate in Psoriasis in a Tertiary Care Teaching Hospital

Methotrexate treatment provokes apoptosis of proliferating keratinocyte in psoriasis patients.

Psoriasis is a chronic inflammatory skin disease characterized by hyper proliferation of keratinocytes. Recent data show that the epidermis thickening in psoriasis may be related to imbalance of homeostasis caused by abnormal apoptotic process. Maintenance of keratinocyte apoptotic process is very important in psoriasis. Methotrexate (MTX) has been used for many years to restore the normal skin in psoriasis condition. However, the exact mechanism of MTX in psoriasis condition is poorly understood. The aim of this study was to examine the role of MTX on keratinocyte apoptosis pathway in psoriasis patients. A total of 58 psoriasis vulgaris patients were recruited for this study. Nonlesional skin biopsies served as control. Skin biopsies of psoriatic patients were collected and analyzed for cytosolic, mitochondria and total cytochrome c by ELISA. Expression of caspase-9, NFκBp65, pAkt1 by western blot, real-time PCR and immunohistochemical analysis of c-FLIP protein was analyzed in nonlesional and lesional skin biopsies before (day 0) and after (at the end of 6 and 12weeks) MTX treatment. After MTX treatment, a significant increase in cytochrome c was observed when compared with before MTX treatment in psoriasis patients (p<0.001). Protein and gene expression of cleaved caspase-9 were significantly increased after MTX treatment, whereas the expression of Bcl-xL, c-FLIP, NFκBp65, pAkt1 significantly downregulated after MTX treatment. In conclusion, these results showed that intrinsic apoptotic pathway induced by MTX eventually adds the beneficial therapeutic role of MTX in psoriasis by controlling the acanthosis.

The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting.

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (<0.4mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti-inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4weeks, then every 3-6months and the liver/renal function test at 3months and then every 6months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to <20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre-conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti-tumour necrosis factor biologics.

Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials.

BackgroundMethotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse.ObjectiveIn order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods).ResultsIn terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time.LimitationsMeta-analyses for efficacy and safety, respectively, employed non-identical selection criteria.ConclusionsThese meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes.