류마티스 관절염 환자에서 획득 후 엄격한 질병 활동 제어를 위한 부울 완화에 대한 시간 길이의 영향
May 28, 2024Scientific Reports 13권, 기사 번호: 13908(2023) 이 기사 인용
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류마티스 관절염(RA) 환자의 질병 활성도 조절, 일상 활동 및 삶의 질 유지에 대한 치료에서 표적 치료(T2T) 전략에 따른 개시부터 임상적 관해(TL) 획득까지의 기간의 임상적 중요성을 조사했습니다. 한 번 이상 불리언 완화를 달성한 환자의 경우, 시작 시 TL과 환자의 배경 데이터 간의 관계, TL과 평균 단순화된 질병 활동 점수(SDAI), 건강 평가 설문지 장애 지수(HAQ-DI) 점수, 통증 점수 간의 관계 첫 관해 이후의 시각적 아날로그 척도(PS-VAS), Sharp/van der Heijde 점수(SHS) 및 삶의 질 점수(QOLS)를 통계적으로 평가했습니다. 환자는 TL이 6개월 이내인지 여부에 따라 두 그룹으로 나뉘었습니다(G ≤ 6 및 G > 6). 두 그룹 간의 첫 번째 관해 후 매개변수의 변화와 불리언 관해율(BRR)을 통계적으로 비교했습니다. 465명의 환자에서 TL은 관해 후 SDAI 점수, HAQ 점수, PS-VAS, SHS 및 QOLS와 유의한 상관관계가 있었습니다. 관해 후 SDAI 점수와 BRR은 G > 6보다 G ≤ 6에서 훨씬 더 좋았습니다. TL은 T2T 치료에서 양호하고 안정적인 임상 과정을 보장하는 중요한 열쇠입니다.
류마티스 관절염(RA)1,2,3,4,5 치료의 초기 목표는 임상적 관해가 되어야 한다는 데 폭넓은 합의가 있습니다. 왜냐하면 대부분의 임상 실습 및 시험에서 방사선학적 손상 장애 및 질병에 대해 임상적 관해를 달성하는 이점이 보고되었기 때문입니다. 일일 활동 유지 관리6,7,8,9,10,11,12,13,14. 임상적 완화는 부울 기준, 단순화된 질병 활동 지수(SDAI) 점수10, 15, 16, 임상 질병 활동 지수(CDAI) 점수16 및 C 반응성 단백질(DAS28-CRP)을 사용한 28-관절 질병 활동 점수17로 지수화됩니다. 임상 실습에서 임상적 완화를 유지하는 것은 관절의 방사선학적 파괴, 일상 생활 활동(ADL) 및 삶의 질(QOL)을 개선하는 RA 환자의 치료 목표입니다18,19,20,21,22,23 . 이러한 환자의 경우 부울 완화 기준이 가장 엄격한 기준이 될 수 있으며, 이는 질병 활동과 방사선학적 진행 모두에 대해 더 나은 임상 결과를 보장할 것입니다21, 24,25,26.
이와는 대조적으로, 류마티스 전문의를 처음 방문한 후 3~6개월 이내에 RA의 임상적 관해가 달성되어야 한다는 EULAR(European League Against Rheumatism)의 강력한 권고에도 불구하고3,4,5 조기 임상적 관해 달성이 에 미치는 영향은 다음과 같습니다. 임상 결과가 충분히 논의되지 않았습니다. 문헌에서는 임상적 관해의 조기 획득이 엄격한 질병 관리의 결과로 더 나은 임상 결과를 얻을 수 있다고 제시하고 있지만27 이는 T2T(Training-to-target) 전략을 옹호하기 전에 보고되었습니다. 우리가 아는 한, T2T 전략에 따른 임상 관해의 조기 달성이 포괄적인 임상 과정에 미치는 영향을 보고한 연구는 없습니다.
따라서 우리는 소규모 코호트 데이터를 사용하여 이 문제를 조사했습니다. 부울 관해를 달성하기 위한 기간이 임상 결과에 미치는 영향을 통계적으로 평가하고 달성하는 데 3~6개월이 적절한 목표인 이유에 대해 논의했습니다.
총 685명의 RA 환자가 모집되었습니다. 이들 중 465명의 환자가 한 번 이상 부울 관해를 달성했습니다. 전체 환자 465명 중 여성은 343명(73.7%)이었고, 평균 연령은 67.8세(21~95세)였다. 이 환자들은 연구에서 분석되었습니다. 초진 시 평균 유병기간은 6.1년(1개월~45년)이었으며, 초진 시 불리언 관해를 보인 예는 없었다. 평균 항순환 시트룰린화 펩타이드 항체(ACPA) 역가는 197.4 U/L이었으며, 336명(72.3%)명의 환자가 ACPA 양성인 반면, 평균 RF 역가는 95.2 IU/mL, 350명(75.3%)명의 환자가 양성이었습니다. RF용. 평균 추적 기간은 71.5개월(범위 36~122개월, 중앙값 85개월)이었고, 첫 방문부터 첫 번째 불리언 완화까지의 평균 기간은 8.1개월(범위 1~111개월, 중앙값 4개월)이었습니다. 평균 SDAI 점수, 건강 평가 설문지 장애 지수(HAQ-DI) 점수, 시각적 아날로그 척도(PS-VAS)를 사용한 통증 점수, Sharp/van der Heijde 점수(SHS) 및 삶의 질 점수(QOLS) 첫 번째 방문은 표 1에 나와 있습니다.
6 groups revealed that the disease duration, HAQ-DI score, PS-VAS, and SHS at baseline in the G > 6 were significantly higher than that in the G ≤ 6 group, and QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group at baseline (Table 1). Similarly, the HAQ-DI score, SHS, and PS-VAS at the first Boolean remission in the G > 6 group were significantly higher than that in the G ≤ 6 group, whereas QOLS in the G ≤ 6 group demonstrated no significant difference compared with that in the G > 6 group. In summarize, the G > 6 group had different characteristics at baseline from the G ≤ 6 group had such as longer disease history, higher joint deformity, inferior pain, ALD, and QOL profile, yet no difference in disease activity between the two groups was shown. For treatment detail, mean MTX dosage and b/tsDMARD administration rate in the G > 6 group were significantly higher than those in the G ≤ 6 group at the first Boolean remission, despite there being no significant difference between the two groups at baseline. The other parameters showed no significant differences between the two groups (Table 4)./p> 6 group was significantly higher than that in the G ≤ 6 group. Similarly, the SDAI score, the HAQ-DI score, PS-VAS, and SHS after the first Boolean remission to the last observation in the G > 6 group were also significantly higher than those in the G ≤ 6 group, and the mean value of the QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group. The Boolean remission rate and SDAI remission rate after the first Boolean remission to the last observation were significantly higher in the G ≤ 6 group than those in the G > 6 group (Table 4). The change of the SDAI score from the first Boolean remission to after the remission was significantly lower in the G ≤ 6 group than that in the G > 6 group, whereas the changes in the HAQ-DI score, PS-VAS, SHS, and QOLS demonstrated no significant differences between the two groups (Table 5)./p> 6 group (p < 0.001), and QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group (p < 0.01). The change value of the SDAI score in the G ≤ 6 group was significantly lower than that in the G > 6 group at any moment from one to three years after the first Boolean remission (p < 0.001). The SDAI scores at one to three year after compared to that at the first Boolean remission were significantly higher in both groups (p < 0.001), whereas the PS-VAS after the first Boolean remission was significantly higher than that at the remission, and the p-values were < 0.05, < 0.05, and < 0.001 at one, two, and three years after, respectively. The QOLS three years after compared to that at the first remission was significantly lower in both groups, and the p-value was < 0.01 and < 0.05 in the G ≤ 6 group and G > 6 group, respectively (Fig. 2)./p> 6. Error bars that show standard deviation in each group were shown at each moment. Except for the SDAI score at the first Boolean remission, mean values of all parameters at any moment were significantly lower in the G ≤ 6 group than those in the G > 6 group (p < 0.001), and the QOLS was significantly higher at any moment in the G ≤ 6 group the those in the G > 6 group at any moment (p < 0.01). Change of mean SDAI score was significantly lower in the G ≤ 6 than in the G > 6 (p < 0.001), and change of the other parameters such as HAQ-DI, PS-VAS, SHS, and QOLS demonstrated no significant difference between the two groups. Statical significances of time change at each moment after the first Boolean remission (BL) for each parameter in the each group compared to the values at the BL were symbolized in the figure (*p < 0.5; **p < 0.01; ***p < 0.001)./p> 3 years, 465 (67.9%) showed Boolean remission once or more, it is realistic, because patients were picked up from various background. That is different from clinical trial study background. Therefore, it can be considered that such a high rate in both of G ≤ 6 and G > 6 groups are realistic given that the Boolean remission achievement rate after the first Boolean remission to the last observation was 62.0% and 43.4%, respectively. However, it is also a fact that some patients could not unfortunately achieve clinical remission, or Boolean remission for some reason such as the reason of patient's personal characteristics, or for some refractory disease status. These patients were excluded from the study./p> 6 months. These results showed that the group who achieved it within 6 months showed significantly better disease activity compared with the group that required > 6 months. The secondary endpoints of the HAQ-DI score, PS-VAS, SHS, and QOLS also showed significantly superior results. However, above all, these parameters were significantly superior in the group that achieved remission within 6 months even at the baseline, and these differences were maintained throughout the treatment./p> 6 group./p> 6 group, despite these parameters demonstrated no significant difference between the two groups at baseline. This may be because the goal of Boolean remission resulted in the need for more intensive treatment compared with the G ≤ 6 group. However, the patient’s drug adherence was not considered in the study. There is a wide variability of drug adherence in patients, which strongly influences clinical results41. Previous treatment including b/tsDMARD administration at baseline did not influence on the time length. Like these, treatment initiation before disease activity gets high may have no influence on the time length because no disease activity difference at baseline was demonstrated between the two groups. The treatment protocol in the study was commonly designed under the T2T strategy, so every patient recruited in the study accepted shared decision-making and had been treated in targeted clinical remission. It seems to be clear that patient-related outcomes (PRO) such as PS-VAS and QOLS, are rather important for obtaining shorter time length. These parameters and the SHS score throughout treatment from baseline to after the first Boolean remission acquisition demonstrated a significant correlation with the time length. These results suggested that a patient who has good PROs from the baseline is well responsible for treatment when tight disease control is targeted./p> 6 group, and this trend persisted after the remission. The parameters improved until the acquisition of Boolean remission and progressively deteriorated after acquisition (Table 5). These parameters after the first remission were significantly correlated with the time length, as shown in Table 3, and parameters other than the SDAI score already showed the same trend at baseline. One confounding factor was mean disease duration at baseline because G > 6 was significantly longer than G ≤ 6. Duration of disease was significantly correlated with all parameters except QOLS (Table 7). This suggested that patients with a longer history obtained a Boolean remission but had a relatively worse clinical course than those with a shorter history./p> 3 years, in the observational study. The time length from the first visit to the first Boolean remission was calculated. The relationship between the time length and each of the background parameters at baseline such as sex, age, disease duration of RA, SHS at the first visit, ACPA, rheumatoid factor (RF), TJC, SJC, PGA, EGA, CRP, SDAI, HAQ-DI, PS-VAS, SHS, and QOLS were evaluated statistically using univariate linear regression analysis, and then multivariate linear regression analysis was performed to evaluate the relationship between the time length and the parameters that demonstrated significant correlation in the univariate model. All data were collected retrospectively from the medical record./p> 6 groups based on the time length for the achievement of first Boolean remission within two groups: G ≤ 6, a patient group who attained Boolean remission within 6 months from the first visit; G > 6, a patient group who attained Boolean remission more than 6 months from the first visit. The two groups were compared with regard to the SDAI score, the HAQ-DI score, PS-VAS, SHS, and QOLS at the first visit and at the time of first Boolean remission, and the values of these parameters at 1–3 years and the mean values of these parameters after the first Boolean remission were assessed using the Mann–Whitney U test. Repeated measures of ANOVA were used for statistical procedures to evaluate the change of these parameters between the moments. Methotrexate (MTX), biologic/targeted disease-modifying anti-rheumatic drug (b/tsDMARD), and glucocorticoid steroid (GCS) administration rate at the first visit were also compared between the two groups using Mann–Whitney U-test. Moreover, changes in these parameters from the first Boolean remission to thereafter between the two groups were also compared using the Mann–Whitney U test. Rates of treatment with mean doses of b/tsDMARD, MTX, and GCS administration rate and mean dose of administration at the first Boolean remission and thereafter between the two groups were also compared using the Mann–Whitney U and chi-square tests. The mean Boolean remission rate after the first remission, and SDAI remission rate at the first Boolean remission and thereafter were also compared between the two groups using the Mann–Whitney U test. The primary endpoint was the mean value of the SDAI score after the first Boolean remission to the last observation, and secondary endpoints included the mean values of the HAQ-DI score, PS-VAS, SHS, and QOLS after the first Boolean remission./p>3.0.CO;2-F" data-track-action="article reference" href="https://doi.org/10.1002%2F1529-0131%28199909%2942%3A9%3C1854%3A%3AAID-ANR9%3E3.0.CO%3B2-F" aria-label="Article reference 8" data-doi="10.1002/1529-0131(199909)42:93.0.CO;2-F"Article CAS PubMed Google Scholar /p>3.0.CO;2-L" data-track-action="article reference" href="https://doi.org/10.1002%2F1529-0131%28200109%2944%3A9%3C2009%3A%3AAID-ART349%3E3.0.CO%3B2-L" aria-label="Article reference 44" data-doi="10.1002/1529-0131(200109)44:93.0.CO;2-L"Article CAS PubMed Google Scholar /p>
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