関節リウマチ患者における感染後の疾患活動性の厳密な制御に対するブール寛解までの期間の影響

May 28, 2024

Scientific Reports volume 13、記事番号: 13908 (2023) この記事を引用

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関節リウマチ（RA）患者の治療において、Treat-to-target（T2T）戦略での開始から臨床的寛解（TL）獲得までの期間が、疾患活動性の制御、日常生活活動、生活の質の維持に関して臨床的に重要であることが調査された。 1 回以上ブール寛解を達成した患者において、TL と開始時の患者の背景データとの関係、および TL と平均単純化疾患活動性スコア (SDAI)、健康評価アンケート障害指数 (HAQ-DI) スコア、痛みスコアとの関係初回寛解時およびその後の視覚的アナログスケール（PS-VAS）、シャープ/ファンデルハイデスコア（SHS）および生活の質スコア（QOLS）を統計的に評価した。患者は、TL が 6 か月以内かそれ以上かどうかに応じて 2 つのグループに分けられました (G ≤ 6 および G > 6)。 2 つのグループ間の最初の寛解後のパラメーターの変化とブール寛解率 (BRR) を統計的に比較しました。 465人の患者において、TLは寛解後のSDAIスコア、HAQスコア、PS-VAS、SHS、およびQOLSと有意に相関した。寛解後の SDAI スコアと BRR は、G > 6 よりも G ≦ 6 の方が有意に優れていました。TL は、T2T での治療において良好で安定した臨床経過を保証する重要な鍵です。

関節リウマチ (RA) の治療の最初の目標は臨床的寛解であるべきであるという広範なコンセンサスがあります 1,2,3,4,5。なぜなら、臨床実践や試験の大部分が、X 線損傷障害および臨床的寛解を達成することの利点を報告しているからです。日常活動の維持6、7、8、9、10、11、12、13、14。臨床的寛解は、ブール基準、簡易疾患活動性指数 (SDAI) スコア 10、15、16、臨床疾患活動性指数 (CDAI) スコア 16、および C 反応性タンパク質 (DAS28-CRP) を使用した 28 関節疾患活動性スコア 17 によって指標付けされます。臨床現場では、臨床的寛解を維持することが RA 患者の治療目標であり、X 線撮影による関節破壊、日常生活活動 (ADL)、および生活の質 (QOL) を改善します 18,19,20,21,22,23。。これらの患者にとって、ブール寛解基準は最も厳しい基準となる可能性があり、疾患活動性と X 線撮影による進行の両方についてより良い臨床転帰が保証されるでしょう 21、24、25、26。

対照的に、欧州リウマチ連盟 (EULAR) は、関節リウマチの臨床的寛解はリウマチ専門医の初診から 3 ～ 6 か月以内に達成されるべきであると強く推奨しているにもかかわらず 3,4,5、早期に臨床的寛解を達成することの影響は、臨床転帰については十分に議論されていません。文献では、臨床的寛解を早期に獲得すると、厳格な疾患管理の結果としてより良い臨床転帰を達成できることが示唆されていますが 27 、これは治療対標的 (T2T) 戦略を提唱する前に報告されたものです。私たちの知る限り、T2T 戦略に基づく早期の臨床寛解達成が包括的な臨床経過に及ぼす影響を報告した研究はありません。

したがって、私たちは小規模なコホートデータを使用してこの問題を調査しました。ブール寛解を達成するまでの期間が臨床転帰に及ぼす影響が統計的に評価され、達成までに 3 ～ 6 か月が適切な目標である理由が議論されました。

合計 685 人の RA 患者が募集されました。これらのうち、465 人の患者が 1 回以上ブール寛解を達成しました。患者465名のうち女性は343名（73.7％）で、平均年齢は67.8歳（21～95歳の範囲）であった。研究ではこれらの患者が分析されました。初回来院時の平均罹患期間は6.1年(1ヶ月から45年の範囲)であり、初回来院時にブール寛解を示した症例はなかった。抗環状シトルリン化ペプチド抗体 (ACPA) の平均力価は 197.4 U/L で、336 人 (72.3%) の患者が ACPA 陽性であったのに対し、平均 RF 力価は 95.2 IU/mL で、350 人 (75.3%) の患者が陽性でした。 RF用。平均追跡調査期間は71.5か月（範囲36～122か月、中央値85か月）、初回来院から最初のブール寛解までの平均期間は8.1か月（範囲1～111か月、中央値4か月）でした。平均SDAIスコア、健康評価アンケート障害指数（HAQ-DI）スコア、視覚的アナログスケールを使用した疼痛スコア（PS-VAS）、シャープ/ファンデルハイデスコア（SHS）、および生活の質スコア（QOLS）最初の訪問を表 1 に示します。

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>

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