Abstract: BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disease characterized by joint pain, swelling, and dysfunction. Acupuncture, as a traditional medical treatment, has proved its effectiveness and safety in many diseases. However, the efficacy of acupuncture in the treatment of rheumatoid arthritis remains controversial. Therefore, the purpose of this study is to evaluate and explore the effect of Tiaodu Tongmai acupuncture in the treatment of preclinical rheumatoid arthritis of different ages through the generalized estimating equation, and to provide a basis for the application of acupuncture in rheumatoid arthritis.
OBJECTIVE: To investigate the effect of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis (pre-RA) patients at different ages based on generalized estimating equation. 
METHODS: A total of 123 patients with preclinical rheumatoid arthritis treated from January to September 2023 were selected as the study objects and divided into study group (n=64) and control group (n=59) according to different treatment methods. The study group was given Tiaodu Tongmai acupuncture treatment, and the control group was given acetaminophen tablets. The baseline balance was adjusted by propensity score matching method. The clinical efficacy and cytokine levels before and after treatment between the two groups were compared. The generalized estimating equation model was established to evaluate the efficacy of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis patients at different ages.
RESULTS AND CONCLUSION: (1) After 0 days of treatment, there were significant differences in joint pain and C-reactive protein expression between study and control groups (P < 0.05). After 4 weeks of treatment, there were significant differences in visual analogue scale scores, joint pain, C-reactive protein and erythrocyte sedimentation rate between the two groups (P < 0.05). After 8 weeks of treatment, there were significant differences in visual analogue scale scores, C-reactive protein and erythrocyte sedimentation rate between the two groups (P < 0.05). After 12 weeks of treatment, there were significant differences in visual analogue scale scores, C-reactive protein and erythrocyte sedimentation rate between the two groups (P < 0.05). (2) The total effective rate of the study group was 93.75%, while that of the control group was 79.17%. The clinical efficacy of the study group was significantly better than that of the control group (P < 0.05). (3) There were significant differences in interleukin-6, interferon-γ, macrophage migration inhibitory factor, rheumatoid factor IgA, rheumatoid factor IgM, metallomatrix proteinase 3, metallomatrix proteinase 9, and anti-cyclic citrulline antibody in the study group before and after treatment (P < 0.05). The levels of interleukin-6, interferon-γ, rheumatoid factor IgA, rheumatoid factor IgM, metallomatrix proteinase 3, metallomatrix proteinase 9, and anti-cyclic citrulline antibody in the control group after treatment were significantly different from those before treatment (P < 0.05). There were significant differences in interleukin-6, interferon-γ, macrophage migration inhibitory factor, rheumatoid factor IgA, rheumatoid factor IgM, metallomatrix proteinase 3, and anti-cyclic citrulline antibody between the two groups after treatment (P < 0.05). (4) After 12 weeks of treatment, the comprehensive efficacy of patients of all ages in the study group was better than that of the control group (P < 0.05). After 8 weeks of treatment, the comprehensive efficacy of patients aged 23-35, 36-50, and 51-60 years old in the study group was better than that of the control group (P < 0.05), and the comprehensive efficacy of patients aged 18-22 years old was comparable between the two groups. After 4 weeks of treatment, the comprehensive efficacy of patients aged 36-50 and 51-60 years old in the study group was better than that of the control group (P < 0.05), and the comprehensive efficacy was comparable between the two groups of patients aged 18-22 and 23-35 years. Overall, Tiaodu Tongmai acupuncture therapy has advantages in treating preclinical rheumatoid arthritis patients aged 36-50 and 51-60 years.

Key words: generalized estimating equation, acupuncture, Tiaodu Tongmai acupuncture therapy, rheumatoid arthritis, preclinical rheumatoid arthritis, age grading, therapeutic effect