O impacto do tempo de remissão booleana para o controle rígido da atividade da doença após a aquisição em pacientes com artrite reumatóide
May 28, 2024Scientific Reports volume 13, Artigo número: 13908 (2023) Citar este artigo
54 acessos
Detalhes das métricas
A importância clínica do tempo desde o início da estratégia de tratamento até o alvo (T2T) até a aquisição da remissão clínica (TL) no tratamento de pacientes com artrite reumatóide (AR) no controle da atividade da doença, atividades diárias e manutenção da qualidade de vida foi investigada. Em pacientes que alcançaram remissão booleana uma ou mais, relação entre TL e dados de base dos pacientes no início, e relação entre TL e pontuação média simplificada de atividade da doença (SDAI), pontuação do Índice de Incapacidade do Questionário de Avaliação de Saúde (HAQ-DI), pontuação de dor com escala visual analógica (PS-VAS), escore de Sharp/van der Heijde (SHS) e escore de qualidade de vida (QVL) na primeira remissão e posteriormente foram avaliados estatisticamente. Os pacientes foram divididos em dois grupos, independentemente de a LT ter ocorrido dentro de 6 meses ou mais (G ≤ 6 e G > 6). A mudança dos parâmetros e a taxa de remissão booleana (BRR) após a primeira remissão entre os dois grupos foram comparadas estatisticamente. Em 465 pacientes, o TL correlacionou-se significativamente com o escore SDAI, o escore HAQ, PS-VAS, SHS e a QVL após a remissão. O escore SDAI e o BRR após a remissão foram significativamente melhores no G ≤ 6 do que no G > 6. O TL é uma chave importante para garantir uma evolução clínica boa e estável no tratamento sob T2T.
Há um amplo consenso de que a remissão clínica deve ser o objetivo inicial para o tratamento da artrite reumatóide (AR)1,2,3,4,5, porque a maioria das práticas clínicas e ensaios relataram o benefício de atingir a remissão clínica no distúrbio do dano radiográfico e manutenção das atividades diárias6,7,8,9,10,11,12,13,14. A remissão clínica é indexada com critérios booleanos, pontuação do índice simplificado de atividade da doença (SDAI)10, 15, 16, pontuação do índice de atividade clínica da doença (CDAI)16 e pontuação da atividade da doença em 28 articulações usando proteína C reativa (DAS28-CRP)17. Na prática clínica, manter a remissão clínica é o objetivo do tratamento para pacientes com AR que melhoraria a destruição radiográfica das articulações, as atividades diárias da vida (AVD) e a qualidade de vida (QV)18,19,20,21,22,23 . Para esses pacientes, os critérios de remissão booleanos podem ser os critérios mais rigorosos e garantiriam melhores resultados clínicos tanto para a atividade da doença quanto para a progressão radiográfica21, 24,25,26.
Em contraste, apesar da forte recomendação da Liga Europeia Contra o Reumatismo (EULAR) de que a remissão clínica na AR deve ser alcançada dentro de 3-6 meses a partir da primeira visita a um reumatologista3,4,5, o impacto da obtenção precoce da remissão clínica na os resultados clínicos não são discutidos o suficiente. Embora na literatura seja sugerido que a aquisição precoce da remissão clínica possa alcançar melhores resultados clínicos como resultado do controle rígido da doença27, isso foi relatado antes de defender a estratégia de tratamento para o alvo (T2T). Até onde sabemos, nenhum estudo relatou o impacto da obtenção precoce da remissão clínica sob a estratégia T2T em cursos clínicos abrangentes.
Portanto, investigamos esse problema usando pequenos dados de coorte; o impacto do tempo para alcançar a remissão booleana no resultado clínico foi avaliado estatisticamente e discutido por que 3 a 6 meses para atingir é uma meta apropriada.
Um total de 685 pacientes com AR foram recrutados. Destes, 465 pacientes alcançaram a remissão booleana uma ou mais vezes. Dos 465 pacientes, 343 (73,7%) eram do sexo feminino e a média de idade foi de 67,8 anos (variando de 21 a 95 anos). Esses pacientes foram analisados no estudo. A duração média da doença na primeira consulta foi de 6,1 anos (variação de 1 mês a 45 anos), e não houve nenhum caso que demonstrasse remissão booleana na primeira consulta. O título médio de anticorpos antipeptídeo citrulinado cíclico (ACPA) foi de 197,4 U/L, e 336 (72,3%) pacientes foram positivos para ACPA, enquanto o título médio de FR foi de 95,2 UI/mL, e 350 (75,3%) pacientes foram positivos. para RF. O tempo médio de acompanhamento foi de 71,5 meses (variação de 36 a 122 meses; mediana de 85 meses) e o tempo médio desde a primeira visita até a primeira remissão booleana foi de 8,1 meses (variação de 1 a 111 meses; mediana de 4 meses). A pontuação média do SDAI, a pontuação do Índice de Incapacidade do Questionário de Avaliação de Saúde (HAQ-DI), a pontuação de dor usando uma escala visual analógica (PS-VAS), a pontuação de Sharp/van der Heijde (SHS) e a pontuação de qualidade de vida (QOLS) em a primeira visita foram mostradas na Tabela 1.
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>
English
Français
Deutsch
Español
Italiano
日本語
한국어
Русский
