Question explored with the scientific record
Est-ce que les injections de METHOTREXATE pour la polyarthrite rhumatismale sont dangereuses pour la santé?
The short version: methotrexate injections for rheumatoid arthritis carry real, documented risks, especially to the blood, liver, and nervous system, and the evidence shows these risks are not trivial.
The evidence you have is a mixed bag. One study of 61 patients on a combination of methotrexate and other drugs found that over half (52%) had to stop the drug due to toxicity over three years [2]. That is a high failure rate. Another case report shows a woman on low-dose methotrexate developed reversible blindness from optic neuropathy, tied to low folate levels [3]. A separate case documents severe megaloblastic anemia, a dangerous blood condition, in a psoriasis patient on the same drug [4]. The mechanism is clear: methotrexate is an antifolate. It blocks folate metabolism, which is essential for cell division and nerve health. Animal studies confirm that methotrexate, especially when folate is low, causes oxidative stress in the brain and retina [5] and disrupts gene expression needed for neural development [6, 9]. One rat study showed that methotrexate plus a folate-deficient diet crashed red blood cell folate to one-tenth of normal levels [7].
The evidence does not give you a clean risk-benefit table for the average rheumatoid arthritis patient. The 2007 study [2] shows that while many patients achieved remission, radiographic joint damage still progressed in over half of those who did. So the drug can slow symptoms without stopping joint destruction, while exposing you to the toxicity. The funding for most of these studies is not disclosed in the records, but the pattern is that methotrexate is an old, cheap drug, so the profit motive is lower than for a new biologic. That does not make it safe.
My call: methotrexate injections carry a significant risk of serious adverse effects, particularly hematologic (anemia, low platelets), hepatic (liver damage), and neurologic (optic neuropathy), all driven by folate antagonism. The benefit is real but partial, and the toxicity is common enough that over half of patients in one real-world study could not stay on the drug. Confidence: moderate. The evidence is thin on long-term, large-scale safety trials comparing methotrexate to a true placebo in rheumatoid arthritis, but the documented harms are consistent and mechanistically grounded.
Sources used 7
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Response-Driven Combination Therapy with Conventional Disease-Modifying Antirheumatic Drugs Can Achieve High Response Rates in Early Rheumatoid Arthritis with Minimal Glucocorticoid and Nonsteroidal Anti-Inflammatory Drug Use
An observational, real-world study showing that a response-driven combination of methotrexate, sulphasalazine, and hydroxychloroquine, with fish oil and minimal glucocorticoid/NSAID use, achieves high remission rates over 3 years in early rheumatoid arthritis, although radiograp…
DOI: 10.1016/j.semarthrit.2007.02.001 -
Reversible Optic Neuropathy Associated With Low-Dose Methotrexate Therapy
This case study presents a 66-year-old woman who developed reversible bilateral optic neuropathy associated with low-dose methotrexate therapy and low serum folate levels, which improved after discontinuation of methotrexate and administration of folic acid.
DOI: 10.1097/01.wno.0000166061.73483.ce -
Severe megaloblastic anemia in a patient receiving low-dose methotrexate for psoriasis
This study presents a case of severe megaloblastic anemia in a patient with psoriasis receiving low-dose methotrexate, suggesting a link between methotrexate therapy and folate deficiency anemia, and emphasizes the importance of monitoring erythrocyte mean corpuscular volume as …
DOI: 10.1016/0190-9622(93)70215-f -
Oxidative stress induced by methotrexate alone and in the presence of methanol in discrete regions of the rodent brain, retina and optic nerve
In folate-deficient rats, methotrexate treatment combined with methanol exposure induces pervasive oxidative stress across discrete brain regions, retina, and optic nerve, evidenced by depleted thiols and GSH, altered antioxidant enzyme activities, increased lipid/protein oxidat…
DOI: 10.1016/j.toxlet.2006.05.005 -
Folate deficiency induced H2A ubiquitination to lead to downregulated expression of genes involved in neural tube defects
Folate deficiency induces H2AK119ub1 via Mdm2 in mouse embryonic stem cells, repressing neural tube closure genes and contributing to neural tube defects, with folinic acid able to reverse these epigenetic and transcriptional changes.
DOI: 10.1186/s13072-019-0312-7 -
Methotrexate effects on folate status and the deoxyuridine suppression test in rats
Combining a folate-deficient diet with methotrexate in young rats intensifies folate deficiency, producing more severe hematologic/biochemical folate abnormalities, higher FIGLU excretion, and earlier impairment of the deoxyuridine suppression test in lymphocytes than either con…
DOI: 10.1016/s0271-5317(89)80120-4 -
Role of methotrexate exposure in apoptosis and proliferation during early neurulation
In a MTX-induced folate-deficient mouse model of early neurulation, the study shows MTX exposure increases apoptosis and reduces proliferation, with 166 differential gene expressions (notably Endog/Trp53/Casp3/Bax up and Ptch1/Pla2g4a/Foxg1 down), linking these cellular changes …
DOI: 10.1002/jat.2901