Clinical research on three traditional Chinese medicine formulas for the prevention and treatment of rheumatoid arthritis

Background Rheumatoid arthritis (RA) is a prevalent autoimmune disorder characterized by chronic inflammation, progressive joint damage, and a high rate of disability. In China, the early diagnosis rate of RA remains low, leading to delayed treatment initiation and suboptimal disease management. Consequently, many patients experience persistent disease activity and frequent relapses, significantly impacting their quality of life. Objective To evaluate the efficacy and safety of three Traditional Chinese Medicine (TCM) formulations in the treatment of RA with different TCM syndromes. Methods The research team conducted three single-center, self-controlled clinical trials. Formula A Trial: This trial enrolled adult participants who tested positive for anti-CCP antibodies or rheumatoid factor (RF) but did not meet the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA). Participants either presented with no arthralgia or experienced arthralgia without synovitis. None of the participants had previously received disease-modifying antirheumatic drug (DMARD) therapy. All participants underwent 12 weeks of treatment with Formula A. The primary outcome was the Disease Activity Score 28 using C-reactive protein (DAS28-CRP), while secondary outcomes included the number of tender and swollen joints (28-joint count), patient-reported resting pain intensity, and duration of morning stiffness. Formula B and C Trials: These trials included adult participants diagnosed with RA according to the 2010 ACR/EULAR classification criteria, exhibiting low to moderate disease activity (DAS28-CRP between 2.6 and 5.1). Participants were either DMARD-naïve or had discontinued DMARD therapy for over one month. Both trials administered either Formula B or Formula C for 12 weeks. The primary outcome was DAS28-CRP, with secondary outcomes encompassing the number of tender and swollen joints (28-joint count), patient-reported resting pain intensity, and duration of morning stiffness. Results Treatment with Formula A demonstrated a significant reduction in morning stiffness duration in RA patients at weeks 4 and 12 ( P = 0.003 and P = 0.001, respectively), compared with baseline. In contrast, Formula B and Formula C showed a downward trend in morning stiffness duration, but the differences were not statistically significant ( P = 0.085 and P = 0.289, respectively). Additionally, Formula C significantly improved the TJC score at week 12 ( P = 0.028), whereas Formula A and B showed no statistically significant changes over time ( P = 0.99 and P = 0.459, respectively). DAS28-CRP scores exhibited a decreasing trend in all three groups at week 12, but the changes were not statistically significant ( P = 0.367, P = 0.441, and P = 0.581, respectively). Furthermore, levels of hs-CRP, RF, and anti-CCP showed fluctuations in each group but without statistical significance. Notably, no clinically meaningful improvements were observed in PhGADA, PAGADA, HAQ, or rest pain across groups. Importantly, no severe adverse events or deaths were reported in any group. Mild to moderate adverse events occurred in 33.33% of patients in the Formula A group, 23.08% in the Formula B group, and 36.36% in the Formula C group. Most commonly reported events included gastrointestinal symptoms, abnormal urine routine, and mild elevation of blood urea nitrogen. All events resolved with symptomatic management, and follow-up assessments returned to normal. No patient discontinued due to adverse events. Conclusion Formula A and C were well-tolerated and showed potential in alleviating RA-related symptoms after 12 weeks of treatment, particularly in morning stiffness and joint tenderness.