This study is the first real-world head-to-head study on the subject of "comparison of efficacy between tofatib and baretinib". The results showed that in patients with RA, the safety of baretinib was equivalent to that of tofatib, but the clinical efficacy of baretinib was better.
In addition, drug resistance was associated with high HAQ-DI score at baseline, the use of multiple bdmards and the use of tofatib. The drug resistance of patients in the tofatib group was related to the use of multiple bdmards, while the drug resistance of patients in the baretinib group was not related to this.
Finally, the authors point out that the efficacy of tofatib may be poor in RA patients who have used multiple bdmards.
Tofatib and barretinib are two core members of Janus kinase inhibitor (jaki), which have been widely used in the treatment of rheumatoid arthritis (RA) in many countries and regions. For RA patients with poor response to anti rheumatic drugs (DMARDs) such as methotrexate and biological agents, the efficacy of tofatib and barretinib has been confirmed. But is there any difference between jaki and jaki?
In this context, Japanese scholars conducted a real-world head-to-head study to compare the clinical efficacy of tofatib and barretinib, and to explore the factors related to drug resistance. The results were recently published in the journal Ann Rheum dis. (impact factor 16.102).
Research Introduction
The efficacy and safety of tofatib group (156 RA patients) and barretinib group (138 RA patients) were compared. The follow-up time was ≥ 6 months. The inverse probability of treatment weighting (iptw) was used to analyze the data to reduce bias. Gaussian mixture model (GMM) was used to analyze the clinical disease activity index (CDAI) trajectories of the two groups. Related adverse events were evaluated according to common adverse event evaluation criteria (CTCAE). The primary end point was the improvement of the two groups at 24 weeks (remission: CDAI ≤ 2.8; low disease activity [LDA]: CDAI ≤ 10.0).
Research results
➤Comparison of effectiveness and safety
In terms of efficacy, the proportion of patients with LDA in tofatib group was significantly lower than that in baretinib group (69.2% vs 81.2%, P = 0.02); The average CDAI of patients in tofatib group was significantly higher than that in barretinib group (8.2 vs 6.2, P = 0.04). There was no significant difference in the proportion of patients who achieved remission between the two groups.
The 24 week follow-up data showed that there was no significant difference in drug retention between the two groups (P = 0.31). In terms of safety, the incidence of grade ≤ 2 adverse events in baretinib group was significantly lower than that in tofatib group (P = 0.04), and there was no significant difference in the incidence of serious adverse events such as severe infection between the two groups (P = 0.15).
➤ Comparison of effectiveness and safety after iptw correction
Iptw was used to correct patient characteristics such as gender, age and course of disease. The data showed that after jaki treatment, the levels of CDAI and C-reactive protein in the two groups were significantly improved. At 24 weeks, the proportion of patients with remission and LDA in baretinib group was significantly higher than that in tofatib group.
After adjustment, there was no significant difference in drug retention rate between the two groups at 24 weeks (P = 0.22); There was no significant difference in the incidence of adverse events leading to jaki discontinuation between the two groups.
➤ The change trajectory of CDAI in the two groups was analyzed by GMM
Based on GMM, all patients were divided into three groups: group 1 (patients with moderate disease activity showed improvement immediately after jaki treatment and reached LDA at 24 weeks), group 2 (patients with high disease activity showed improvement immediately after jaki treatment and reached LDA at 24 weeks) and group 3 (treatment resistant group: showed partial response to jaki treatment and did not reach LDA at 24 weeks).
Comparing the proportion of patients in three groups between tofatib group and barretinib group, the proportion of patients with drug resistance in barretinib group was significantly lower than that in tofatib group (P = 0.02); There was no significant difference between group 1 and group 2.
Among all patients, the possible factors for drug resistance included high HAQ-DI score at baseline (P = 0.02), use of multiple bdmards (P = 0.002) and use of tofatib (P = 0.03). The analysis of single treatment group showed that the drug resistance of patients in tofatib group was related to the use of multiple bdmards (P < 0.001); There were no factors related to drug resistance in barretinib group.
Research conclusion
This study is the first real-world study to compare the clinical efficacy of barretinib and tofatib head-to-head. The data show that the safety of baretinib is equivalent to that of tofatib, and the clinical efficacy of baretinib is better. The study corrected patient characteristics through iptw to reduce or eliminate bias as much as possible, but there may still be some unknown confounding factors. In addition, due to the limitations such as study sample size and regional restrictions, the conclusions of the study still need to be confirmed by more studies. Based on GMM, it is found that patients are less likely to be resistant to baretinib than tofatib, and patients who have used multiple bdmards may be more likely to be resistant to tofatib.
