Recently, a patient asked, “I’ve heard that subcutaneous MTX is more effective than oral medication”. This study is the latest to be published in the leading rheumatology journal ARD. OBJECTIVE: To compare the safety, relative bioavailability, and tolerability of oral methotrexate (MTX) and subcutaneous MTX (autoinjector) for the treatment of rheumatoid arthritis (RA). METHODS: This was a randomized, multicenter, open, three-way crossover study in which adult RA patients >18 years of age received >3 months of MTX at 10 mg, 15 mg, 20 mg, and 25 mg weekly treatment, randomized to three treatment modalities: oral, subcutaneous abdominal, and subcutaneous thigh injections. Pharmacokinetic analysis and injection site assessment were performed after 24 hours of each treatment. RESULTS: A total of 47 patients completed the study. Systemic drug exposure to oral MTX stalled at doses greater than 15 mg/week. In contrast, subcutaneous systemic drug exposure to MTX increased linearly, with better subcutaneous than oral systemic drug exposure at the same dose. No serious adverse events were observed in each observation group. CONCLUSION: Unlike oral MTX, systemic drug exposure does not stagnate with subcutaneous MTX injections, especially at doses greater than 15 mg/week. In the present study, higher systemic MTX exposure was not associated with increased adverse events. Therefore, patients with RA may benefit better by switching to subcutaneous MTX when the clinical efficacy of oral MTX is poor. Commentary: This article is a recent study published in the leading rheumatology journal ARD that evaluated the efficacy and safety of oral MTX and subcutaneous MTX. The information we obtained from this literature was mainly that systemic exposure to subcutaneous injectable drugs was significantly better than oral MTX at >15 mg weekly MTX administration without an increase in clinical adverse events. Here, I would like to state my opinion: 1. What is drug systemic exposure? In order to better understand this study, it is important to talk to you a little about this pharmacokinetic concept. Pharmacokinetic exposure refers to the area under the drug concentration-time curve (AUC), which represents the total amount of absorption after a single dose and reflects the degree of absorption of the drug. 2. Is it applicable to current clinical practice and should patients be in a hurry to switch their medication method? Firstly, the subcutaneous injection used in this study is an automatic subcutaneous injector, which is very convenient for patients to self-administer after learning, which solves the trouble of going to the hospital for subcutaneous injection; secondly, the study shows that the systemic exposure of MTX is better than oral administration only at >15 mg. Usually the dose of MTX administered abroad for the treatment of RA is greater than that in China, while domestic RA patients usually receive MTX at a dose of about 10-15 mg; finally, the small sample size and limited observation time of this study also have limitations. Therefore, oral MTX is still a very safe and effective way to treat RA in China at present.