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DRUG:

leflunomide

i
Other names: HWA 486, SU 101, SU101, HWA486, SU-101, HWA-486
Associations
Company:
Generic mfg.
Drug class:
DHODH inhibitor
Associations
14d
NECESSITY: New Clinical End-points in Patients With Primary Sjögren's Syndrome (clinicaltrials.gov)
P2, N=300, Recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Feb 2024 --> Apr 2025
Trial completion date • Trial primary completion date
|
hydroxychloroquine • leflunomide
1m
New P2 trial
|
leflunomide
2ms
Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response (clinicaltrials.gov)
P3, N=400, Recruiting, University of Nebraska | Trial primary completion date: Mar 2026 --> Mar 2027
Trial primary completion date
|
CRP (C-reactive protein)
|
Rituxan (rituximab) • hydroxychloroquine • tofacitinib • Kevzara (sarilumab) • leflunomide
2ms
A randomized controlled trial of csDMARDs combined with Tripterygium glycoside tablets in the treatment of rheumatoid arthritis (ChiCTR2400088173)
P=N/A, N=188, Not yet recruiting, Dongzhimen Hospital, Beijing University of Chinese Medicine; Dongzhimen Hospital, Beijing University of Chinese Medicine
New trial
|
IL6 (Interleukin 6)
|
methotrexate • hydroxychloroquine • leflunomide
2ms
Leflunomide in Treating Patients with Steroid Dependent Chronic Graft Versus Host Disease (clinicaltrials.gov)
P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2024 --> Nov 2024
Trial completion date • Trial primary completion date • IO biomarker
|
leflunomide
3ms
Metabolic syndrome and psoriatic arthritis: the role of weight loss as a disease-modifying therapy. (PubMed, Ther Adv Musculoskelet Dis)
Leflunomide has been shown to reduce body weight but also increase blood pressure...Dietary and exercise modifications are the cornerstone of weight management but vary substantially across individuals. Novel therapies to treat weight loss, such as glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors, may prove useful alongside disease-modifying therapies for those with PsA and MetS and should be investigated as potential therapeutic adjuncts.
Review • Journal
|
IL17A (Interleukin 17A) • IL23A (Interleukin 23 Subunit Alpha)
|
leflunomide
3ms
The Effect of Cilostazol on Rheumatoid Arthritis Patients (clinicaltrials.gov)
P2/3, N=70, Active, not recruiting, Ain Shams University | Recruiting --> Active, not recruiting | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024
Enrollment closed • Trial completion date • Trial primary completion date
|
CRP (C-reactive protein)
|
leflunomide
3ms
Leflunomide, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
P2, N=29, Recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Feb 2027 | Trial primary completion date: Jun 2024 --> Feb 2027
Trial completion date • Trial primary completion date
|
pomalidomide • leflunomide
4ms
Comparison of disease-modifying anti-rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats. (PubMed, Clin Exp Pharmacol Physiol)
Some groups received HBOT, whereas others were given etanercept or leflunomide. The X-ray images revealed improvements in joint structure, and the histopathological analysis showed reduced inflammation and collagen abnormalities. Combining DMARD with HBOT had similar effects to individual therapies, suggesting a cost-effective and potentially safer approach for improving outcomes in rats with RA.
Clinical • Preclinical • Journal
|
IL1B (Interleukin 1, beta)
|
leflunomide
4ms
Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy (clinicaltrials.gov)
P1/2, N=2, Completed, City of Hope Medical Center | Terminated --> Completed
Trial completion
|
leflunomide
5ms
New P1 trial • Metastases
|
gemcitabine • leflunomide
6ms
Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients (clinicaltrials.gov)
P2, N=56, Recruiting, City of Hope Medical Center | N=20 --> 56 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Enrollment change • Trial completion date • Trial primary completion date
|
leflunomide
6ms
Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy (clinicaltrials.gov)
P1/2, N=2, Terminated, City of Hope Medical Center | Trial completion date: Jun 2024 --> Jun 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Jun 2023; Accrual rate is too slow.
Trial completion date • Trial termination • Trial primary completion date
|
leflunomide
7ms
Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma (clinicaltrials.gov)
P1, N=1, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date
|
leflunomide
8ms
Leflunomide in Treating Patients With Steroid Dependent Chronic Graft Versus Host Disease (clinicaltrials.gov)
P1, N=18, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting
Enrollment closed
|
leflunomide
8ms
Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases. (PubMed, Vaccines (Basel))
Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination...In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments.
Review • Journal • Immunomodulating
|
IL6 (Interleukin 6)
|
Rituxan (rituximab) • methotrexate • leflunomide
8ms
Efficacy and safety of pharmacological treatment of psoriatic arthritis: a systematic literature research informing the 2023 update of the EULAR recommendations for the management of psoriatic arthritis. (PubMed, Ann Rheum Dis)
The results of this SLR informed the task force responsible for the 2023 update of the European Alliance of Associations for Rheumatology recommendations for pharmacological management of PsA.
Journal
|
IL17A (Interleukin 17A) • IL23A (Interleukin 23 Subunit Alpha)
|
methotrexate • tofacitinib • Cosentyx (secukinumab) • Ilumya (tildrakizumab-asmn) • leflunomide
9ms
Leflunomide induced cardiac injury in adult male mice and bioinformatic approach identifying Nrf2/NF-κB signaling interplay. (PubMed, Toxicol Mech Methods)
Histopathological results confirmed the dose-dependent effects of LFND on cardiac muscle structure in the form of cytoplasmic, nuclear and vascular changes in addition to increased collagen deposits and apoptosis which were increased compared to controls especially with LFND 10 mg/kg. The current study elicits the dose-dependent cardiac injury induced by LFND administration with and highlighted, for the first time, dysregulation in Nrf2/NF-κB signaling.
Preclinical • Journal
|
TNFA (Tumor Necrosis Factor-Alpha) • BAX (BCL2-associated X protein)
|
BAX expression
|
leflunomide
9ms
Leflunomide in Mild COVID-19 Patients (clinicaltrials.gov)
P1, N=11, Terminated, University of Chicago | N=20 --> 11 | Recruiting --> Terminated; Terminated by PI
Enrollment change • Trial termination
|
leflunomide
10ms
New P2 trial
|
KRAS (KRAS proto-oncogene GTPase)
|
Avastin (bevacizumab) • hydroxychloroquine • leflunomide
10ms
Effectiveness of Tofacitinib in Patients Initiating Therapy for Psoriatic Arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. (PubMed, Rheumatol Ther)
This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias.
Journal
|
TNFA (Tumor Necrosis Factor-Alpha) • IL17A (Interleukin 17A)
|
methotrexate • tofacitinib • leflunomide
11ms
Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response (clinicaltrials.gov)
P3, N=400, Recruiting, University of Nebraska | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2025 --> Mar 2026
Trial completion date • Trial primary completion date
|
CRP (C-reactive protein)
|
Rituxan (rituximab) • hydroxychloroquine • tofacitinib • Kevzara (sarilumab) • leflunomide • minocycline
11ms
Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy (clinicaltrials.gov)
P1/2, N=2, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024
Trial completion date • Trial primary completion date
|
leflunomide
11ms
Leflunomide in Patients With PTEN-null Advanced Solid Malignancies (clinicaltrials.gov)
P1, N=24, Recruiting, Deborah Doroshow | Phase classification: P1a/1b --> P1
Phase classification • Metastases
|
PTEN (Phosphatase and tensin homolog)
|
PTEN expression
|
leflunomide
11ms
Effectiveness of tofacitinib combined with iguratimod in the treatment of difficult-to-treat moderate-to-severe rheumatoid arthritis (PubMed, Beijing Da Xue Xue Bao Yi Xue Ban)
Iguratimod combined with tofacitinib in the treatment of difficult-to-treat moderate-to-severe RA may have efficacy. The machanism was improving the patients' recent clinical symptoms by reducing inflammatory indexes. This combination treatment regimen with iguratimod and tofacitinib has a good safety profile.
Journal
|
CRP (C-reactive protein)
|
methotrexate • tofacitinib • leflunomide
11ms
Telitacicept Study in Chinese Subjects With Systemic Lupus Erythematosus (clinicaltrials.gov)
P1, N=92, Completed, RemeGen Co., Ltd. | Recruiting --> Completed
Trial completion • Trial completion date • Trial primary completion date
|
cyclophosphamide • leflunomide
12ms
An injectable subcutaneous colon-specific immune niche for the treatment of ulcerative colitis. (PubMed, Nat Biomed Eng)
Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix and nanofibres functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth factor-beta 1, and the immunosuppressive small-molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals' lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive T cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon's lamina propria, promoting the recovery of epithelial damage. The bioengineered niche also prevented colitis-associated colorectal cancer and eliminated immune-related colitis triggered by kinase inhibitors and immune checkpoint blockade.
Journal
|
PD-L1 (Programmed death ligand 1) • TGFB1 (Transforming Growth Factor Beta 1) • CD86 (CD86 Molecule)
|
leflunomide
12ms
Leflunomide for the Treatment of Relapsed or Refractory CD30+ Lymphoproliferative Disorders (clinicaltrials.gov)
P2, N=1, Completed, City of Hope Medical Center | Active, not recruiting --> Completed
Trial completion
|
TNFRSF8 (TNF Receptor Superfamily Member 8)
|
leflunomide
12ms
Severe Psoriatic Arthritis - Early intervEntion to Control Disease: the SPEED Trial (clinicaltrials.gov)
P4, N=315, Recruiting, University of Oxford | Trial completion date: Aug 2023 --> Feb 2025 | Trial primary completion date: Aug 2023 --> Aug 2024
Trial completion date • Trial primary completion date
|
leflunomide
12ms
Effect of acupuncture on arthritic pathological injury in rats with type Ⅱ collagen-induced rheumatoid arthritis. (PubMed, Zhen Ci Yan Jiu)
Acupuncture stimulation can improve the degree of joint inflammation and swelling in CIA rats, which may be related to its effects in inhibiting the overexpression of immunoinflammatory factors in serum and regulating expression of mt-p53, NF-κB p65, PPARγ mRNAs and proteins in the synovial tissue.
Preclinical • Journal
|
TP53 (Tumor protein P53) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL17A (Interleukin 17A) • PPARG (Peroxisome Proliferator Activated Receptor Gamma)
|
TP53 expression • IL6 expression
|
leflunomide
12ms
Network-Based In Silico Analysis of New Combinations of Modern Drug Targets with Methotrexate for Response-Based Treatment of Rheumatoid Arthritis. (PubMed, J Pers Med)
New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy.
Review • Journal
|
TYMS (Thymidylate Synthetase) • SYK (Spleen tyrosine kinase) • NLRP3 (NLR Family Pyrin Domain Containing 3)
|
Rituxan (rituximab) • methotrexate • hydroxychloroquine • Actemra IV (tocilizumab) • fenebrutinib (RG7845) • leflunomide • mavrilimumab (KPL-301)
1year
CD19/BCMA CAR-T Cell Therapy for Refractory Systemic Lupus Erythematosus - Safety and Preliminary Efficacy Data from a Phase I Clinical Study (ASH 2023)
After lymphodepleting chemotherapy with cyclophosphamide/fludarabine (D-4 to D-2), patients receive a single infusion of 1-2x106 CD19 CAR-T cells and BCMA CAR-T cells per kilogram of body weight at D0...All patients had active severe SLE and had received glucocorticoids, hydroxychloroquine, tacrolimus, total glucosides of paeony, merti-macrolide, leflunomide, azathioprine, methotrexate, cyclophosphamide, immunoglobulin, rituximab, belimumab, and Tetracycline before treatment with CAR-T cells, which were standard treatments that were either ineffective or difficult to withdraw.3 patients received 1x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells, and 9 patients received 2x10^6/kg of each of CD19 CAR-T cells and BCMA CAR-T cells 2x10^6/kg... These data suggest that CD19/BCMA CAR-T cell therapy is well tolerated and can induce rapid and durable remission in severe refractory SLE.
Clinical • P1 data • CAR T-Cell Therapy
|
Rituxan (rituximab) • cyclophosphamide • methotrexate • hydroxychloroquine • fludarabine IV • CD19/BCMA targeted CAR T-cells • leflunomide
1year
Leflunomide in Treating Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
P1/2, N=12, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | N=39 --> 12
Trial completion • Enrollment change
|
leflunomide
1year
Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy (clinicaltrials.gov)
P1/2, N=2, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2023 --> Dec 2023 | Trial primary completion date: Sep 2023 --> Dec 2023
Trial completion date • Trial primary completion date
|
leflunomide
1year
Leflunomide in Patients With PTEN-null Advanced Solid Malignancies (clinicaltrials.gov)
P1a/1b, N=24, Recruiting, Deborah Doroshow | Trial primary completion date: Sep 2023 --> Sep 2026
Trial primary completion date • Metastases
|
PTEN (Phosphatase and tensin homolog)
|
PTEN expression
|
leflunomide
over1year
Solid Lipid Nanoparticles Embedded Hydrogels as a Promising Carrier for Retarding Irritation of Leflunomide. (PubMed, Gels)
To assess the skin safety of fabricated lipidic formulation, irritation potential was performed employing the HET-CAM technique. In conclusion, the findings of this investigation demonstrated that LEF-SLN hydrogel is capable of enhancing the photostability of the entrapped drug while reducing its skin irritation with improved topical delivery characteristics.
Journal
|
leflunomide
over1year
Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma (clinicaltrials.gov)
P1, N=1, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Jun 2023 --> Dec 2023
Trial completion date • Trial primary completion date
|
leflunomide
over1year
Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies (clinicaltrials.gov)
P1, N=18, Recruiting, City of Hope Medical Center | Trial completion date: Oct 2023 --> Jul 2025 | Trial primary completion date: Oct 2023 --> Jul 2025
Trial completion date • Trial primary completion date • Combination therapy
|
leflunomide
over1year
Leflunomide in Previously Treated Metastatic Triple Negative Cancers (clinicaltrials.gov)
P1/2, N=54, Recruiting, Joseph Sparano | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2023 --> Oct 2025
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
|
ER positive • HER-2 negative • PIK3CA mutation
|
leflunomide
over1year
Arterial wall fibrosis in Takayasu arteritis and its potential for therapeutic modulation. (PubMed, Front Immunol)
The Th17 and Th1 lymphocytes in TAK demonstrate an activation of mammalian target organ of rapamycin 1 (mTORC1) driven by Notch-1 upregulation. In vitro experiments suggest the potential to target arterial wall fibrosis in TAK with leflunomide, tofacitinib, baricitinib, or mTORC1 inhibitors. Since arterial wall inflammation is followed by fibrosis, a strategy of combining immunosuppressive agents with drugs that have an antifibrotic effect merits exploration in future clinical trials of TAK.
Review • Journal
|
NOTCH1 (Notch 1) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TGFB1 (Transforming Growth Factor Beta 1) • GPNMB (Glycoprotein Nmb) • IL17A (Interleukin 17A)
|
sirolimus • tofacitinib • leflunomide
over1year
Lysyl oxidase-like 3 restrains mitochondrial ferroptosis to promote liver cancer chemoresistance by stabilizing dihydroorotate dehydrogenase. (PubMed, Nat Commun)
CRISPR-Cas9-mediated site-mutation of mouse LOXL3-S704 to D704 causes a reduction in lipid peroxidation. Using an advanced liver cancer mouse model, we further reveal that low-dose Oxaliplatin in combination with the DHODH-inhibitor Leflunomide effectively inhibit liver cancer progression by inducing ferroptosis, with increased chemotherapy sensitivity and decreased chemotherapy toxicity.
Journal
|
oxaliplatin • leflunomide