L'impatto della durata del tempo sulla remissione booleana per uno stretto controllo dell'attività della malattia dopo l'acquisizione nei pazienti con artrite reumatoide
May 28, 2024Rapporti scientifici volume 13, numero articolo: 13908 (2023) Citare questo articolo
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È stata studiata l’importanza clinica del periodo di tempo dall’inizio della strategia Treat-to-Target (T2T) all’acquisizione della remissione clinica (TL) nel trattamento di pazienti con artrite reumatoide (RA) sul controllo dell’attività della malattia, sulle attività quotidiane e sul mantenimento della qualità della vita. Nei pazienti che hanno ottenuto una remissione booleana una o più volte, relazione tra TL e dati di base del paziente all'inizio e relazione tra TL e punteggio medio dell'attività di malattia semplificata (SDAI), punteggio HAQ-DI (Health Assessment Questionnaire Disability Index), punteggio del dolore con la scala analogica visiva (PS-VAS), il punteggio Sharp/van der Heijde (SHS) e il punteggio della qualità della vita (QOLS) alla prima remissione e successivamente sono stati valutati statisticamente. I pazienti sono stati divisi in due gruppi indipendentemente dal fatto che il TL fosse entro 6 mesi o più (G ≤ 6 e G > 6). La variazione dei parametri e il tasso di remissione booleano (BRR) dopo la prima remissione tra i due gruppi sono stati confrontati statisticamente. In 465 pazienti, il TL correlava significativamente con il punteggio SDAI, il punteggio HAQ, PS-VAS, SHS e QOLS dopo la remissione. Il punteggio SDAI e il BRR dopo la remissione erano significativamente migliori nei G ≤ 6 rispetto ai G > 6. Il TL è una chiave importante per garantire un decorso clinico buono e stabile nel trattamento in T2T.
Esiste un ampio consenso sul fatto che la remissione clinica dovrebbe essere l'obiettivo iniziale per il trattamento dell'artrite reumatoide (RA)1,2,3,4,5, poiché la maggior parte delle pratiche cliniche e degli studi clinici hanno riportato il beneficio del raggiungimento della remissione clinica sui disturbi del danno radiografico e mantenimento dell'attività quotidiana6,7,8,9,10,11,12,13,14. La remissione clinica è indicizzata con criteri booleani, punteggio dell'indice di attività della malattia semplificato (SDAI)10, 15, 16, punteggio dell'indice di attività della malattia clinica (CDAI)16 e punteggio dell'attività di malattia di 28 articolazioni utilizzando la proteina C-reattiva (DAS28-CRP)17. Nella pratica clinica, il mantenimento della remissione clinica è l'obiettivo del trattamento per i pazienti con artrite reumatoide che migliorerebbe la distruzione radiografica delle articolazioni, le attività quotidiane della vita (ADL) e la qualità della vita (QOL)18,19,20,21,22,23 . Per questi pazienti, i criteri booleani di remissione potrebbero essere i criteri più rigorosi e garantirebbero risultati clinici migliori sia per l'attività della malattia che per la progressione radiografica21, 24,25,26.
Al contrario, nonostante la forte raccomandazione della Lega Europea contro il Reumatismo (EULAR) secondo cui la remissione clinica nell’artrite reumatoide dovrebbe essere raggiunta entro 3-6 mesi dalla prima visita dal reumatologo3,4,5, l’impatto del raggiungimento precoce della remissione clinica sulla i risultati clinici non sono discussi abbastanza. Sebbene in letteratura si suggerisca che l’acquisizione precoce della remissione clinica possa ottenere risultati clinici migliori come risultato di uno stretto controllo della malattia27, ciò è stato riportato prima di sostenere la strategia Treat-to-Target (T2T). Per quanto ne sappiamo, nessuno studio ha riportato l’impatto del raggiungimento precoce della remissione clinica nell’ambito della strategia T2T su corsi clinici completi.
Pertanto, abbiamo studiato questo problema utilizzando dati di piccola coorte; l'impatto del tempo necessario per ottenere la remissione booleana sull'esito clinico è stato valutato statisticamente e si è discusso del motivo per cui 3-6 mesi per il raggiungimento rappresentano un obiettivo appropriato.
Sono stati reclutati un totale di 685 pazienti con AR. Di questi, 465 pazienti avevano raggiunto una o più remissioni booleane. Su 465 pazienti, le donne erano 343 (73,7%) e l'età media era di 67,8 anni (da 21 a 95 anni). Questi pazienti sono stati analizzati nello studio. La durata media della malattia alla prima visita è stata di 6,1 anni (intervallo da 1 mese a 45 anni) e non vi è stato alcun caso che abbia dimostrato una remissione booleana alla prima visita. Il titolo medio degli anticorpi anti-peptide citrullinato ciclico (ACPA) era 197,4 U/L e 336 (72,3%) pazienti erano positivi per ACPA, mentre il titolo medio RF era 95,2 IU/ml e 350 (75,3%) pazienti erano positivi per RF. La durata media del follow-up è stata di 71,5 mesi (range 36-122 mesi; mediana 85 mesi) e la durata media del tempo dalla prima visita alla prima remissione booleana è stata di 8,1 mesi (range 1-111 mesi; mediana 4 mesi). Il punteggio SDAI medio, il punteggio HAQ-DI (Health Assessment Questionnaire Disability Index), il punteggio del dolore utilizzando una scala analogica visiva (PS-VAS), il punteggio Sharp/van der Heijde (SHS) e il punteggio della qualità della vita (QOLS) a la prima visita sono stati mostrati nella Tabella 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>
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