Title : Ultra-low-dose methotrexate combined with low-dose prednisolone in two distinct chronic disorders: A hypothesis-generating clinical comparison
Abstract:
Background: Prednisolone and methotrexate are established immunomodulatory agents, but methotrexate is conventionally used at weekly doses substantially higher than those described here. Long-term clinical observations prompted exploration of substantially reduced doses in selected chronic disorders.
Clinical observations: Two published cases representing markedly different disease contexts were compared. In a child with Rett syndrome and pharmaco-resistant epilepsy, prolonged treatment with low-dose prednisolone and ultra-low-dose methotrexate was associated with a progressive reduction in seizure generalization and modification of the epileptic pattern. The second case involved childhood-onset Takayasu arteritis with extensive vascular disease and more than four decades of follow-up. Intermittent prednisolone, predominantly at approximately 5 mg/day, and methotrexate initially up to 3.75 mg/week and subsequently reduced to 0.625–2.5 mg/week were used during the long-term course. Despite severe established vascular involvement, prolonged periods of clinical stability and preserved functional independence were observed.
Discussion: These observations involve fundamentally different disorders: a neurodevelopmental condition with neurological and potential neuroimmune components and a systemic large-vessel inflammatory disease. They do not demonstrate efficacy or establish causality. However, the clinical trajectories raise the hypothesis that immunomodulatory activity may persist at methotrexate doses substantially below conventional rheumatological regimens when used in combination with low-dose glucocorticoids.
Conclusion: These hypothesis-generating observations support systematic investigation of ultra-low-dose methotrexate combined with low-dose prednisolone, including dose-response relationships, immunological biomarkers, long-term safety, and reproducibility in defined patient populations.
