To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting.
Multicentric, nationwide, registry-based, ambispective, ...observational study.
Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017.
Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional-hazards model (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events.
Drug retention rate and DRT.
A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence.
Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.
To characterize and describe clinical experience with childhood-onset non-infectious uveitis.
A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 ...hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared.
IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae 28%, cataracts 16%, band keratopathy 14%, ocular hypertension 11% and cystoid macular edema 10%) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (
< 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae 31% and cataracts 9.6%) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use.
Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.
IMPACT-III and IMPACT-III-P are health-related quality of life (HRQoL) questionnaires for patients with pediatric inflammatory bowel disease (p-IBD) and their parents/caregivers. We aimed to perform ...a transcultural adaptation and validation for the Spanish context. Translation, back-translation, and evaluation of the questionnaires were performed by an expert committee and 12 p-IBD families. We recruited p-IBD patients aged 10-17 and their parents/caregivers. Utility, content, and face validity were considered. Validation was performed with Cronbach's alpha coefficient and varimax rotation. We confirmed the adequacy of the factor analysis using Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity tests. A confirmatory factor analysis was performed using the following goodness indexes: chi-square, Normed Fit Index (NFI), Root Mean Square Error of Approximation index (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI). The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed. We included 370 patients and 356 parents/caregivers (37 hospitals). Both questionnaires had good content and face validity and were considered user-friendly. The KMO measure (0.8998 and 0.9228, respectively) and Bartlett's sphericity test (p-value < 0.001 for both) confirmed the adequacy of the factor analysis. The 4-factor model, complying with Kaiser's criterion, explained 89.19% and 88.87% of the variance. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The CFA showed an adequate fit (NFI 0.941 and 0.918, RMSEA 0.048 and 0.053, SRMR 0.037 and 0.044, and CFI 0.879 and 0.913). The correlation coefficient was excellent (0.92).
The SEGHNP versions of IMPACT-III and IMPACT-III-P are valid and reliable instruments for Spanish p-IBD families.
• IMPACT-III and parent-proxy IMPACT-III (IMPACT-III-P) are useful questionnaires for assessing health-related quality of life (HRQoL) in pediatric inflammatory bowel disease (p-IBD) patients and their parents/caregivers and have been translated and validated in several countries. • To date, no transcultural adaptation and validation of these questionnaires have been published for Spanish patients with p-IBD and their families.
• This is the first transcultural adaptation and validation of IMPACT-III and IMPACT-III-P for Spanish p-IBD families. • These are valid and reliable instruments for assessing HRQoL in Spanish families of patients with p-IBD.
Abstract
Background
IMPACT-III and IMPACT-III-P are Health-Related Quality of Life (HRQoL) questionnaires for pediatric Inflammatory Bowel Disease (p-IBD) patients and their parents/caregivers. They ...consist of 35 items answered with a 1-5 points Likert scale that evaluate six domains. Higher scores indicate better HRQoL. IMPACT-III has been translated into over 70 languages and validated in several countries. However, the existing IMPACT-III Spanish translation showed room for improvement and none of the tools had been validated in our population. We aimed to perform a transcultural adaptation and validation of the Spanish versions.
Methods
With permission from the questionnaires’ authors, we performed the translation and back-translation by professional translators, followed by evaluation by an expert committee and a small group of p-IBD families (n=12). Members of the SEGHNP (Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition) were invited to recruit p-IBD patients aged 10-18 and their families (February’21-November’22) to complete the questionnaires. Demographical and clinical data of the p-IBD participants were analyzed. Validation was performed with the Cronbach's alpha coefficient (considering 0.8-0.9 a good internal consistency) and a confirmatory factorial analysis with Varimax rotation (desirable values >0.5). The Kaiser Meyer Olkin (KMO) measure (>0.5 good correlation) and the Bartlett’s sphericity test (p<0.05) were calculated to confirm the adequacy of the factor analysis. The utility (method and completion time) was considered. The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed. Data were collected and analyzed with REDCap and Stata 16.
Results
We included 370 patients and 356 parents/guardians from 37 hospitals. Descriptive statistics of the participants are shown in table 1. The KMO measure (0.8998 and 0.9228, respectively) and the Bartlett's sphericity test (p-value <0.001 for both) confirmed the factor analysis’ adequacy. The factorial model with four factors, complying with Kaiser’s criterion, explained 89.19% and 88.87% of the variance in the model. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The use of a Likert scoring system and the completion median time of 10 minutes for both tools was considered optimal. The correlation coefficient was 0.92, which was considered excellent.
Conclusion
The SEGHNP versions of the IMPACT-III and IMPACT-III-P are valid and reliable to use with Spanish p-IBD families. Our findings suggest a 4-factor scores in both questionnaires, although the optimal factor structure should be further examined. In our sample, parents/caregivers were good proxies for rating their p-IBD children overall HRQoL.
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