In a recent study, researchers found that the drug methotrexate may increase the risk for skin cancer as well as other adverse side effects such as gastrointestinal complications and lung problems.
What is methotrexate?
Methotrexate-based drugs are immunosuppressants that help treat various medical conditions such as rheumatoid arthritis rheumatoid arthritis, and severe psoriasis. It functions by interfering with the growth of rapidly dividing cells, such as cancer cells, and by modulating the immune system, reducing inflammation and immune response.
Methotrexate is classified as an antimetabolite and antifolate drug, and it is administered in various forms, including oral tablets and injectable solutions. Due to its potent effects, methotrexate is typically used under close medical supervision to monitor for potential side effects and ensure its efficacy in managing the specific condition it is prescribed for.
Regular monitoring is essential, especially for long-term users, to manage risks such as liver toxicity, bone marrow suppression, and increased susceptibility to infections.
The Johns Hopkins Arthritis Center estimates that about 60 percent of rheumatoid arthritis patients are currently using or have used these medications. Methotrexate-based brands include Otrexup, Trexall, and Xatmep.
What does methotrexate treat?
In addition to RA, methotrexate is utilized to treat psoriasis, which causes skin inflammation. It does this by slowing skin cell growth to prevent scale formation. Methotrexate is also used to treat various cancers including lung cancer, breast cancer, certain head and neck cancers, certain kinds of lymphoma, and leukemia. It treats cancer by slowing cancer cell growth.
How is it administered? What is the right dose?
Methotrexate can come in either the form of a 2.5-milligram pill, tablet, liquid, or an injection. The recommended dose is once a week. The typical dosage ranges from 3 to 10 pills. However, the individual dose may be split into two or more to avoid side effects and facilitate absorption. Methotrexate may sometimes be administered through escalating doses. For instance, one may take three tablets once a week for a two-week period and increase the dosage to four tablets starting in the third week.
The correct dosage of methotrexate varies widely depending on the condition being treated, the patient’s age, weight, and overall health. For cancer treatment, doses are typically higher and may be administered weekly or in cycles, while for autoimmune diseases like rheumatoid arthritis or psoriasis, lower doses are usually taken once a week.
Dosage adjustments and close monitoring by a healthcare provider are essential to ensure safety and efficacy, as methotrexate can have significant side effects, including liver toxicity and bone marrow suppression. Always follow the prescribing physician’s instructions and undergo regular medical supervision while on methotrexate therapy.
What are some of methotrexates’ side effects?
These are some of methotrexate’s side effects:
Common Side Effects
- Gastrointestinal Issues: Nausea, vomiting, and diarrhea are frequent, particularly when starting treatment.
- Mucositis: Inflammation and ulceration of the mucous membranes, including the mouth, which can lead to sores and discomfort.
- Fatigue: A general feeling of tiredness or weakness is common.
- Skin Reactions: Rash and increased sensitivity to sunlight.
- Elevated Liver Enzymes: Methotrexate can affect liver function, which may be monitored through regular blood tests.
Moderate Side Effects
- Blood Cell Changes: Methotrexate can cause reductions in white blood cells, which fight infection, red blood cells, which can lead to a host of problems with anemia and platelets.
- Pulmonary Symptoms: Cough or shortness of breath; it can rarely cause pulmonary fibrosis.
- Hair Thinning or Loss: Thankfully, this is typically reversible.
Severe Side Effects
- Liver Damage: Long-term use can lead to fibrosis or cirrhosis, necessitating regular monitoring of liver health.
- Kidney Damage: Methotrexate can affect kidney function, which is also monitored via blood tests.
- Neurological Effects: Severe neurological effects are rare but can include seizures or stroke-like symptoms.
- Immunosuppression: Increased susceptibility to infections, sometimes severe.
- Teratogenic Effects: Methotrexate can cause birth defects and is contraindicated during pregnancy and in men planning to father a child.
Patients taking methotrexate are typically monitored closely by their healthcare providers to manage these side effects effectively. Regular blood tests are a crucial part of this monitoring to detect early signs of complications. If any severe symptoms are noticed, such as sudden vision changes, severe breathing problems, or signs of infection, immediate medical attention should be sought.
Does Methotrexate Cause Skin Cancer?
There is evidence linking methotrexate to an increased risk of skin cancer, particularly non-melanoma skin cancers like basal cell carcinoma and squamous cell carcinoma. This risk is more pronounced in patients who are on long-term methotrexate therapy, such as those with rheumatoid arthritis or psoriasis.
Methotrexate’s immunosuppressive properties can reduce the skin’s ability to combat UV-induced damage, potentially leading to an increased risk of developing skin cancer. Patients using methotrexate are often advised to regularly monitor their skin for any changes or abnormalities and to maintain protective measures against UV exposure, such as using sunscreen and wearing protective clothing.
It’s important for patients on methotrexate to have regular dermatological check-ups to detect any early signs of skin cancer. If you or someone you know is concerned about the risk of skin cancer while using methotrexate, discussing these concerns with a healthcare provider is crucial for appropriate management and monitoring.
Methotrexate Study Results
The results of the study raising concerns about the safety of methotrexate were published in March 2020 in the Annals of Internal Medicine. The study was a randomized trial comprised of over 6,000 patients. Each of them had a prior history of heart disease or diabetes. The average age of the patients was 66 years. The researchers gave patients either a low-dose methotrexate or a placebo. All the patients also took a one-milligram dose of folic acid on a daily basis. The researchers tracked the test subjects for about 23 months.
The results showed that 87% of patients who received methotrexate-based drugs suffered an adverse health effect, compared to only 81% of patients who received a placebo. Compared to the placebo group, patients taking methotrexate showed a 50% higher risk for skin cancer, 91% for gastrointestinal issues, 50% for lung complications, and 15% for blood-related conditions. Interestingly, the researchers found that methotrexate reduced the risk of renal adverse effects. They also found no increased risk for other cancers.
2023 Methotrexate Study
Last year, a study titled “Use of methotrexate and risk of skin cancer: a nationwide case-control study” aimed to explore this same question – whether methotrexateis associated with an increased risk of skin cancers like basal cell carcinoma, cutaneous squamous cell carcinoma, and cutaneous malignant melanoma.
Researchers collected data from Danish health records from 2004 to 2018, identifying patients with these skin cancers and matching each with ten control subjects based on sex and birth year.
The analysis showed that the use of MTX was linked to a higher risk of all three types of skin cancers. The study concludes that there is a noticeable increase in the risk of basal cell carcinoma and squamous cell carcinoma associated with methotrexate usage, with the risk growing with higher doses. However, this link is less clear in patients with psoriasis, indicating that individual patient factors might influence cancer risk.
Institute for Safe Medication Practice Report
The Institute for Safe Medication Practice published a report in which researchers found that patient error when taking the wrong methotrexate dosages was very common. They found that six out of fourteen cases involving accidental daily use of methotrexate involved patient error.
The cases involved patients over the age of 65. Older individuals usually take medications daily and may struggle to properly read instructions found on labels. The researchers found that the instructions were confusing. This means a misread of the instructions can be dangerous. They note that the risk was worse if the directions that involve escalating doses. There was one such case of this confusion, which resulted in the patient being hospitalized with hypotension, pancytopenia, and septic shock within five days of taking the medication.
The report also noted that the methotrexate usage nearly doubled from about 560,000 to 1 million patients. This is concerning because more patients may experience these side effects. The study showed that individuals can easily take the wrong doses, which means that more individuals experience methotrexates’ harmful side effects.
Conclusion
There is no question that methotrexate can cause serious conditions like can have serious side effects, including bone marrow suppression, liver and kidney toxicity, pulmonary issues, and an increased risk of infections. Now there is a concern because methotrexate has been linked to an increased risk of skin cancer, particularly non-melanoma types like squamous cell carcinoma and basal cell carcinoma.
This association arises due to the drug’s immunosuppressive properties, which can reduce the body’s ability to repair DNA damage in skin cells, leading to carcinogenesis. Long-term use of methotrexate can thus make the skin more susceptible to cancerous changes.
Patients on methotrexate should undergo regular skin examinations and adopt protective measures against sun exposure to mitigate this risk. Healthcare providers should inform patients about the potential skin cancer risks associated with methotrexate and monitor them closely for any signs of skin abnormalities.
The results of these recent studies may signal tough times ahead for methotrexate drugs. Even smaller doses of methotrexate can increase adverse health effects. At a minimum, these results will probably lead to more in-depth studies about the link between methotrexate and skin cancer as well as other health conditions. This could, although I think it is unlikely, lead to future litigation.