Related Experiment Video
Updated: Dec 28, 2025
06:24
Minimal Erythema Dose MED Testing
Published on: May 28, 2013
42.7K
Adverse Effects of Low-Dose Methotrexate: A Randomized Trial
Daniel H Solomon1, Robert J Glynn1, Elizabeth W Karlson1
1Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., R.J.G., E.W.K., F.L., C.C., J.C., C.X., J.M., N.B., P.F.D., B.M.E., A.D.P., S.P.H., M.M., D.A.R., S.Y.R., A.R., J.A.S., J.S., D.H.S., S.K.T., K.M.V., N.P.P., P.M.R.).
Annals of Internal Medicine
|February 18, 2020
Summary
Low-dose methotrexate (LD-MTX) use in patients with cardiovascular disease showed increased risks for gastrointestinal, pulmonary, infectious, and hematologic adverse events (AEs). However, renal AEs were decreased, and skin cancer risk was elevated.
Area of Science:
- Rheumatology and Pharmacology
- Cardiovascular Disease Research
- Clinical Trial Analysis
Background:
- Low-dose methotrexate (LD-MTX) is a primary treatment for systemic rheumatic diseases, including rheumatoid arthritis.
- Despite widespread use, robust data on adverse event (AE) rates from placebo-controlled trials are limited.
- Understanding LD-MTX risks is crucial for patient safety and treatment optimization.
Purpose of the Study:
- To quantify and compare adverse event (AE) rates and risks between LD-MTX and placebo.
- To identify specific AE profiles associated with LD-MTX in a high-risk population.
- To provide evidence-based insights into the safety of LD-MTX.
Main Methods:
- A double-blind, placebo-controlled, randomized trial (ClinicalTrials.gov: NCT01594333) was conducted in North America.
- Adult participants with cardiovascular disease and diabetes or metabolic syndrome were randomized to LD-MTX (≤20 mg/wk) or placebo, with all receiving folic acid.
- Adverse events were assessed through blinded adjudication, comparing risks between groups over a median follow-up of 23 months.
Main Results:
- Of 4786 participants, 87.0% on LD-MTX and 81.5% on placebo experienced an AE of interest.
- LD-MTX was associated with elevated risks for gastrointestinal (HR, 1.91), pulmonary (HR, 1.52), infectious (HR, 1.15), and hematologic (HR, 1.15) AEs.
- Increased skin cancer risk (HR, 2.05) was observed with LD-MTX, while renal AEs were reduced (HR, 0.85).
Conclusions:
- LD-MTX use in patients without rheumatic disease but with cardiovascular risk factors is linked to increased risks of certain AEs.
- The study highlights a need for careful monitoring of gastrointestinal, pulmonary, infectious, hematologic, and skin adverse events.
- Reduced renal AE risk with LD-MTX suggests potential benefits in specific patient populations, warranting further investigation.
More Related Videos
Related Concept Videos
01:29Therapeutic Drug Monitoring: Affecting Factors
138
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
138
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
403
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
403
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
196
Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
196
01:15Bioavailability Study Design: Healthy Subjects Versus Patients
92
Bioavailability studies are essential for evaluating a drug's therapeutic efficacy and understanding its absorption patterns under various physiological conditions. Conducting such studies on target patient populations provides more relevant data by simulating real-world disease states. However, practical challenges often necessitate the use of young, healthy adult volunteers as study subjects.Patients may exhibit altered drug absorption patterns due to the effects of the disease itself,...
92
01:17Phase II Reactions: Methylation Reactions
615
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
615
01:16Therapeutic Drug Monitoring: Overview and Classification
212
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
212