Other substances

Leflunomide

A dihydroorotate dehydrogenase inhibitor prodrug.

Phase of research

Potential treatment - clinical evidence

How it helps

Other treatment

Drug status

Used to treat other disease

Supporting references

Contradictory references

AI-suggested references

Clinical trials

General information

Leflunomide is a dihydroorotate dehydrogenase inhibitor prodrug. It has immunosuppressive and anti-inflammatory properties (NCIt). Leflunomide is used for treatment of rheumatoid and psoriatic arthritis (LiverTox).

Leflunomide on DrugBank
Leflunomide on PubChem
Leflunomide on Wikipedia

Marketed as

ARAVA

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Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Multi-omics study revealing tissue-dependent putative mechanisms of SARS-CoV-2 drug targets on viral infections and complex diseases Preprint	in silico			May/11/2020
Efficacy and Safety of Leflunomide for Refractory COVID-19: An Open-label Controlled Study Preprint Non-randomized controlled open trial	Patients		effective in enhancing SARS-CoV-2 clearance and hospital discharge in refractory COVID-19 patients	Jun/02/2020

AI-suggested references

Link	Publication date
Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds.	Feb/22/2022
Multiple sclerosis immunomodulatory therapies tested for effectiveness in COVID-19.	Oct/24/2020
Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2.	Aug/04/2020
Inhibition of porcine epidemic diarrhea virus (PEDV) replication by A77 1726 through targeting JAK and Src tyrosine kinases.	Jun/18/2020
A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab	Jun/19/2020
A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial	Jul/21/2020
Seroprevalence of SARS-CoV-2-specific antibodies and vaccination-related adverse events in systemic lupus erythematosus and rheumatoid arthritis	Mar/05/2022
Efficacy and Safety of Leflunomide for Refractory COVID-19: A Pilot Study	Jul/02/2021
Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases	Jul/01/2022

Clinical trials

ID	Title	Status	Phase	Start date	Completion date
NCT04532372	Leflunomide for the Treatment of Severe COVID-19 in Patients With a Concurrent Malignancy	Recruiting	Phase 1\|Phase 2	Oct/23/2020	Sep/18/2022
Alternative id - 20291\|NCI-2020-05746\|P30CA033572 Interventions - Other: Best Practice\|Drug: Leflunomide\|Drug: Placebo Administration Study type - Interventional Study results - No Results Available Locations - City of Hope Medical Center, Duarte, California, United States Study designs - Allocation: Randomized\|Intervention Model: Sequential Assignment\|Masking: Double (Participant, Investigator)\|Primary Purpose: Treatment Enrollment - 30 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Incidence of toxicity, graded according to the NCI CTCAE version 5\|Maximum tolerated dose (MTD) (Phase 1)\|Clinical activity (Response)(Phase 2)\|Time to Clinical activity (Response)\|Overall Survival\|Oxygen Saturation improvement\|SARS-CoV-2 resolution\|Hospitalization\|Mechanical Ventilation required\|Mechanical Ventilation duration\|Vital status (alive/dead)\|Vital status (cause of death)
NCT04361214	Leflunomide in Mild COVID-19 Patients	Recruiting	Phase 1	May/05/2020	Feb/01/2021
Alternative id - IRB20-0622 Interventions - Drug: Leflunomide Study type - Interventional Study results - No Results Available Locations - University of Chicago, Chicago, Illinois, United States Study designs - Allocation: N/A\|Intervention Model: Single Group Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 20 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Tolerability of high dose leflunomide as measured by leflunomide dose modifications\|Tolerability of high dose leflunomide as measured by discontinuation of leflunomide\|Tolerability of high dose leflunomide as measured by Adverse Events\|Time to defervescence as measured in days while on treatment protocol\|Resolution of other COVID-19 symptoms measured in days while on treatment protocol
NCT05007678	Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease	Active, not recruiting	Phase 3	Sep/16/2020	Jul/01/2022
Alternative id - 2020ZC01 Interventions - Drug: leflunomide Study type - Interventional Study results - No Results Available Locations - Ashford and St Peters Hospital NHS Foundation Trust, Chertsey, United Kingdom Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 178 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Time to clinical improvement\|Incidence of adverse events\|Changes in virological load over time

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