Guide
Rheumatoid arthritis (RA) is an autoimmune disease that severely affects the quality of life of patients. In recent years, studies have found that people at high risk of RA can be identified by detecting anti-citrullinated protein antibody (ACPA) and rheumatoid factor in serum, as well as symptoms such as inflammatory joint pain, and early treatment intervention may help delay or prevent the occurrence of RA. At the same time, previous studies have shown that Brazil pro has some efficacy in the treatment of active RA, but its application in high-risk groups has not been fully studied. A randomized, double-blind, placebo-controlled phase 2b clinical trial (APIPPRA) published in the Lancet in 2024 evaluated the feasibility, efficacy, and tolerability of Brazil pro in people at high risk of RA and explored its role in preventing RA progression.
Study design
The APIPPRA study was conducted in 28 hospitals and Netherlands 3 clinics in United Kingdom and enrolled adults ≥ 18 years of age who were at risk for RA (positive for ACPA and rheumatoid factor and had inflammatory joint pain). Participants were randomly assigned (1:1) to either Brazil (125 mg subcutaneously weekly) or placebo for 12 months of treatment, followed by 12 months of follow-up.
≥The primary endpoint of the study was the time to clinical synovitis or progression to RA [according to the United States Society of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria] in 3 joints. Secondary endpoints include the number of swollen joints, the patient's global visual analogue score (VAS), pain VAS, health assessment questionnaire (HAQ), European five-dimensional health scale (EQ-5D), etc.
Findings:
The study ended up including 213 people, 110 who received Brazil platyl and 103 who received placebo.
1
Brazil significantly slows RA progression
The progression-free survival curve of Kaplan-Meier arthritis showed that the proportion of arthritis progression-free in the Brazil group after 24 months of treatment was better than that in the placebo group (p=0.044, see Figure 1). At 12 months, the proportion of arthritis progression was estimated at 92.8% in the Brazil group and 69.2% in the placebo group; At 24 months, 70.4% and 58.5% of arthritis progressed were free of arthritis (see Figure 1). Arthritis-free mean survival was 53 days at 12 months (95% CI 28–78; p<0.0001) and 99 days (95% CI 38–161; p=0.0016) at 24 months in the Brazil group compared with placebo.
Figure 1: Progression-free survival curves for Kaplan-Meier arthritis
At 12 months, the proportion of patients in the placebo group with ≥ number of swollen joints 1, 2, or 3 was higher than that in the Brazil group (Figure 2).
Figure 2: Number of swollen joints at 12 months: Brazil vs. placebo
2
Brazil pro significantly improves patient function and quality of life
Treatment with Brazil for 12 months significantly improved patients' function (see Fig. 3A), pain score (see Fig. 3B, 3D) and quality of life (Fig. 3C, 3D).
Figure 3: Mean change from baseline in secondary outcomes at 24 months
3
Brazil is safe
There were 7 and 11 serious adverse events in the Brazil and placebo groups, respectively, and one death was determined to be unrelated to treatment.
Research Discussion
Studies have shown that Brazil pro in adults at high risk of RA can significantly delay RA progression and improve function and quality of life. Even after discontinuation of treatment, the proportion of RA progression in the Brazil group was lower than that in the placebo group, suggesting that the efficacy could be maintained after discontinuation. On the other hand, studies have shown that Brazil may be treated for more than 12 months to maintain long-term efficacy.
The advantages of the APIPPRA study were the inclusion of ACPA-positive participants, fixed-cycle dosing, participant recruitment consistent with a real-world clinical setting, the adoption of a reliable primary endpoint confirmed by ultrasound, a lower dropout rate before the major event, and an assessment of the effect of the study drug on subclinical synovitis. Ultrasonography was able to identify study participants with no or only low levels of detectable subclinical synovitis, suggesting that the APIPPRA study cohort is representative of the population with minimal joint involvement.
Conclusions of the study
In summary, 12 months of treatment with Brazil Pro can delay the progression of RA in high-risk patients, and the efficacy is maintained for a period of time after the treatment period, and no new safety signals appear. APIPPRA studies have shown that therapeutic intervention during high-risk phases of RA is a viable option.
文献来源：Cope AP, Jasenecova M, Vasconcelos JC, et al. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial. Lancet. 2024; 403(10429):838-849. doi:10.1016/S0140-6736(23)02649-1