methotrexate

It discusses the evidence on pharmacologic treatments, including drugs used for symptomatic relief such as non-steroidal anti-inflammatory drugs, and those used to control the disease process; this last group comprises conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, leflunomide, and sulfasalazine, and biologic and targeted DMARDs, including anti-tumor necrosis factor (TNFα), anti-interleukin-17 (IL-17), anti-IL-12/23, and anti-IL-23 agents, as well as Janus kinase (JAK) inhibitors and phosphodiesterase 4 (PDE4) antagonists. Although these drugs are usually tailored to the clinical profile of the patient, biomarkers predictive of response to therapy are needed so that a more personalized approach can be followed.

A methotrexate (MTX)-loaded dual phosphate- and pH-responsive nanodrug (pHA@MOF-Au/MTX) is next engineered by integrating Fe-based metal-organic frameworks and gold nanoparticles for improved chemo/chemodynamic therapy of TNBC...Furthermore, sequential EGCG and pHA@MOF-Au/MTX treatment showed remarkable anti-tumor effects in a mouse model of TNBC, with a tumor growth inhibition rate of 79.9%, and a pulmonary metastasis rate of 96.8%. Altogether, the combination strategy developed in this study can improve the efficacy of chemo/chemodynamic therapy in TNBC and represents an innovative application of EGCG.

The docking results revealed strong binding affinities of 7-O-methyl-cyanidin-3-O-(2″-galloyl)-galactoside with Keap1 and amentoflavone with MAPK. These insights pave the way for future experimental validation and therapeutic development of sumac-based phytoconstituents against MTX-induced nephrotoxicity.

Venetoclax was given for 21 days with each cycle of mini-hyper-CVD (cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well-tolerated with promising efficacy. NCT03319901.

MTX-LPD can occur in the liver. Clinician should suspect hepatic MTX-LPD when a liver mass is detected in patient who had been treating with MTX for RA.

Dexamethasone (DXM) was used in average-risk 2 (AR2) T-ALL and B-ALL during induction, 10 and 6 mg/m2/day, respectively. Leucovorin rescue was delayed to 42 h instead of 36 h after initiation of high-dose methotrexate, and a postconsolidation MRD time point was added to stratify patients...The HR was 2.15 (99% CI: 0.67-6.85) for very low-risk but 0.34 (99% CI: 0.13-0.89) for AR2. The particularly favorable results observed in the T-ALLs and AR2 subgroups suggest the benefit of using DXM in specific patient groups and highlight the importance of risk stratification.

Adalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy and can be considered a lower target level for therapeutic drug monitoring of adalimumab therapy.

We applied targeted next-generation sequencing for detection of recurrent single nucleotide variants, copy number alterations and zygosity abnormalities in diagnostic specimens from 78 PCNSL patients treated with a standard methotrexate-based regimen, to identify prognostically significant molecular subgroups...These genomic aberrations identify a high-risk molecular subgroup that may inform risk stratification in PCNSL. Further elucidation of the mechanisms of therapeutic resistance associated with the high-risk genetic phenotype is requisite to facilitate precision medicine and progress in therapy.

EBV-associated T-cell lymphoma with haemophagocytic lymphohistiocytosis can affect not only children but also adolescents and young adults, highlighting the need for awareness of the high fatality risk.Early recognition of EBV-associated haemophagocytic lymphohistiocytosis (EBV-HLH) is crucial; when a patient presents with fever, pancytopaenia and hepatosplenomegaly.Future prospective studies are warranted to determine the treatment strategy and the optimal patient population that requires early bone marrow transplantation when initial treatment is inadequate.

He was administered alemtuzumab twice (at the time of initial treatment and relapse) and cyclophosphamide, vincristine, and hydrocortisone chemotherapy. Furthermore, novel therapeutic drugs (venetoclax and tofacitinib) were administered based on previous case reports...Consideration should be given to suspending treatment, adjusting the administration interval, or administering G-CSF if necessary. The treatment interval can be appropriately adjusted, making it a valuable treatment option for refractory T-PLL.

Here we examine the biochemical and cellular effects of a propargyl linked, non-classical antifolate that shows exceptional potency and resilience in the background of methotrexate resistance, UCP1162...Leucovorin suppressed the cellular effects of UCP1162, consistent with UCP1162 working as an antifolate...Long-term exposure to UCP1162 resulted in static culture expressing stem cell genes (CD34, ABCG2, ABCB1), adaptive genes (TCN2, CDKN1A), and genes that might serve as therapeutic targets (TPBG/5T4, TNFRSF10A, ACE). These findings suggest that UCP1162 is a unique tool for studying cellular responses to long-term antifolate treatment and holds promise as a lead compound capable of overcoming some forms of antifolate resistance.

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P3, N=847, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

P3, N=182, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

The combination of MTX and resveratrol effectively attenuated pro-inflammatory activity in THP-1 cells, as evidenced by the downregulation of mRNA and chemokine expression. These findings suggest that the synergistic effects of MTX and resveratrol hold promise for enhancing cancer therapeutics.

Six cycles of the dose-dense methotrexate, vinblastine, adriamycin, and cisplatin-combined chemotherapy were completed after an ultrasound-guided percutaneous biopsy of the renal tumor. After chemotherapy, the size of the original tumor in the right kidney had decreased in size, as well as the other metastatic lesions.

We recently demonstrated that INO can be added safely to a non-myeloablative conditioning of bendamustine, fludarabine, and rituximab in patients with indolent lymphoid malignancies who required an allogeneic hematopoietic transplantation (HCT) (Am J Hematol 2024)...Patients who received transplants from MUDs received an additional dose of methotrexate 5 mg/m2 on day +11 and 1 mg/kg of rabbit anti-thymocyte globulin IV on days -1 and -2 before HCT...The patient who was in CR2 at transplant had Ph+ ALL and was maintained on ponatinib after HCT. Key prior therapies in ALL patients included blinatumomab (n=5) and INO (n=5)... Our conclusions are limited by the small number of patients due to slow accrual. However, our data suggest that INO is safe when combined with a melphalan plus fludarabine HCT conditioning regimen. The survival outcomes are encouraging and need to be validated in a larger number of patients.

Chemotherapy, consisting of doxorubicin, cisplatin and methotrexate (MAP) increased the 5-year osteosarcoma survival rate from 20% to approximately 60% by the 1980s...Patients whose disease fails to respond to MAP receive second-line treatments such as etoposide and, in more recent years, the kinase inhibitor regorafenib...Importantly, we found that inhibition of MCL-1 with the BH3-mimetic S63845 combined with regorafenib significantly prolonged the survival of mice bearing pulmonary osteosarcoma metastases. Together, our results highlight the importance of MCL-1 in osteosarcoma cell survival and present a potential therapeutic avenue that may improve metastatic osteosarcoma patient outcomes.

Their conjugation with the drugs Irinotecan, Imatinib, and Methotrexate was also confirmed using UV-Vis, FTIR, and Dynamic light scattering (DLS). The result of the methylthiazol tetrazolium (MTT) assay showed that conjugated AgNPs and AuNPs with Irinotecan had a higher toxic effect on the A549 cancer cell line than AgNPs and AuNPs conjugated with Imatinib. This study provides a promising avenue for further investigation and development of nanoparticle-drug conjugates as a potential cancer immunotherapy strategy.

Additionally, NOP58 was linked to drug responses, including Methotrexate, Rapamycin, Sorafenib, and Vorinostat. Its expression level serves as a reliable prognostic biomarker and an actionable therapeutic target, advancing precision medicine for prostate cancer. Targeting NOP58 may enhance therapeutic efficacy and improve outcomes in oncology.

HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.

P2, N=300, Suspended, National Cancer Institute (NCI) | N=550 --> 300

ERβ activation was found to reduce the expression of GULP1 as a direct downstream target in bladder cancer cells, resulting in the induction of cisplatin resistance.

If a daily prednisone dose of >10 mg is required for >6 months to maintain remission, it is best to use a second-line drug such as methotrexate or azathioprine. Anti-tumor necrosis factor agents, such as infliximab or adalimumab, may be used to treat inflammatory disease that persists on combination treatment with glucocorticoids and a second-line agent.

P1, N=24, Recruiting, City of Hope Medical Center | Active, not recruiting --> Recruiting | Trial completion date: Aug 2025 --> Feb 2026 | Trial primary completion date: Aug 2025 --> Feb 2026

P2, N=50, Active, not recruiting, Yancheng First People's Hospital | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jun 2023 --> Dec 2023

A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin...CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.

With respect to immunosuppressive treatment used to control RA, it was observed that glucocorticoids (especially high-dose usage) and Rituximab (RTX) predispose the patients to poor SARS-CoV-2 outcomes, as opposed to Baricitinib and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) inhibitors. COVID-19 vaccination has proven effective and generally safe for RA patients in some studies, although therapies with Methotrexate (MTX), Abatacept (ABA), and RTX have been associated with impaired vaccine immune response. This systematic literature review brings updated and thorough information with respect to the immunological, clinical, and management of a complex immune-mediated inflammatory disease (IMID) like RA in the setting of COVID-19 and underlines the challenges faced by this group of patients. The lessons learned can be extended beyond the pandemic in shaping a more informed and compassionate healthcare system and offering long-term medical care for patients with RA.

Here, in this study, we investigated the detrimental impact of an 8-week chronic unpredictable stress (CUS) protocol on the progression of arthritis and psoriasis using collagen-induced arthritis (CIA) and imiquimod (IMQ)-induced psoriasis rat models, respectively. Moreover, the therapeutic efficacy of MTX was notably reduced in stressed rats compared to non-stressed, underscoring the detrimental effects of chronic stress on treatment outcomes. Taken together, our results emphasize the importance of considering chronic stress as a critical factor in the management of autoimmune diseases.

Our results indicate that there is a statistically significant correlation between the rs1131596 SLC19A1 polymorphism and the development of MTX-induced hepatotoxicity (p = 0.03), but there is no significant association between any of the studied polymorphisms and mucositis or other side effects, such as nausea, emesis, diarrhea, neutropenia, skin rash and infections. In addition, when genotype TT of rs1131596 and genotype AA of rs56292801 are both present in a patient then there is a higher risk of developing severe hepatotoxicity (p = 0.0104).

Methods SD rats were randomized into normal control, model, methotrexate (MTX) and HQGP groups, with 6 rats in each group...In myocardial tissue, the expression of GAS5 increased significantly, the expression of miR-21 decreased significantly, the release of LDH, the mRNA and protein levels of TLR4, NF-κB p65, caspase-1 and NLRP3 decreased significantly, and the mRNA expression of GSDMD reduced while the protein level significantly reduced. Conclusion HQGP improves myocardial injury in AA rats by inhibiting miR-21/TLR4 signalling through up-regulation of lncRNA GAS5, inhibiting pyroptosis, and reducing pro-inflammatory cytokine expression.

P2, N=72, Completed, Astellas Pharma Inc | Phase classification: P2a --> P2

Data on the use of zoledronic acid (ZA) in juvenile CRMO are scarce...The patient's condition stayed stable while taking naproxen (20 mg/kg/day) and methotrexate (10 mg/week) for 1.5 years until he experienced right elbow pain, swelling, no overlying skin erythema, and a restricted range of motion...Non-steroidal anti-inflammatory drugs and methotrexate were initially effective in treating our patient's condition, but a recurrence necessitated treatment modification. To the best of our knowledge, this case is the first documented instance of the use of ZA in CRMO in Iraq and Arab nations.

Apart from methotrexate (MTX) and biologics such as tumor necrosis factor (TNFi), interleukin-12/23 (IL-12/23i), and IL-17 inhibitors (IL-17i), traditionally used for the treatment of PsA, recently biologics such as IL-23i and targeted synthetic agents like JAK inhibitors (JAKi) have been introduced in the daily clinical practice for the treatment of this disease...While IL-23i has not been shown to increase the risk for common or opportunistic infections, a well-established association of JAKi with herpes zoster warrants the attention of rheumatologists. In this narrative review, we summarize the infectious complications of available treatment options by drug class in patients with PsA.

Various therapies have been discovered for psoriasis, including topical treatments, phototherapy, conventional systemic agents such as methotrexate, retinoids and ciclosporine, as well as biologics...Ruxolitinib cream has been investigated in various dermatologic diseases, including atopic dermatitis, vitiligo, psoriasis, and alopecia areata. However, there is limited data on the efficacy of oral ruxolitinib in patients with psoriasis vulgaris. Here, we report a patient diagnosed with myelofibrosis coexisting with psoriasis vulgaris, successfully treated with oral ruxolitinib.

P2, N=379, Completed, Astellas Pharma Inc | Phase classification: P2b --> P2

And the use of methotrexate (MTX) can restore the heterochromatin state altered by LAP2α depletion...These results indicate the important role of LAP2α in regulating ALT activity and offer insights into the interplay between lamina-associated proteins and telomeres in maintaining telomere length. Importantly, our findings may help identify a more appropriate target population for the osteosarcoma therapeutic drug, MTX.

In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

P4, N=182, Recruiting, Medical University of Vienna

LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.

P4, N=44, Not yet recruiting, Tanta University

P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2028 | Initiation date: Oct 2024 --> Jan 2025 | Trial primary completion date: Dec 2027 --> Dec 2028