Why carry out this study? |
To further strengthen and enlarge evidence on the effectiveness of adalimumab in pediatric patients with chronic non-infectious posterior uveitis and panuveitis. |
What was learned from the study? |
Adalimumab was efficacious and tolerated in reducing ocular inflammation, especially in the retina, and significantly improved long-term visual acuity in pediatric patients with chronic non-infectious posterior uveitis and panuveitis. |
Adalimumab demonstrated limited superiority over conventional adalimumab-free treatment in terms of reducing macular edema in pediatric patients with non-infectious posterior uveitis and panuveitis. |
Although it took a few weeks to regulate inflammation, adalimumab assured a high response rate of remission and long-term remission stability in pediatric patients with non-infectious posterior uveitis and panuveitis. |
Introduction
Methods
Patient Selection
Drug Use and Follow-up
Data Collection
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Visual acuity: The logarithm of the minimum angle of resolution (logMAR) was used to assess BCVA. The “counting finger/hand motion/light perception” was converted to a quantified visual acuity value [17].
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Intraocular inflammation: The Nussenblatt scale and Standardization of Uveitis Nomenclature Working Group schema were used to assess the degree of vitritis and anterior chamber inflammation, respectively [16]. The definition of alleviation of inflammation included patients who achieved either complete absence of inflammation or ≥ 2-step decrease in inflammation (anterior chamber score and vitreous haze score) or slight remnants (0.5 + anterior chamber cells). Relapse of uveitis was defined as a new flare or aggravation of uveitis, including a two-step increase in the inflammation level of anterior chamber cells and/or vitreous haze or an increase from grade 3 + to 4 + , retinal vasculitis, optic disc, or macular edema.
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CMT: CMT was defined as the average retinal thickness within a 1-mm-diameter region in the macular fovea measured using Cirrus High-Definition-OCT (Carl Zeiss AG, Jena, Germany).
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FA scores of posterior inflammation: oral or intravenous FA examination was performed at baseline and every half year following ADA administration. Angiography Scoring for Uveitis Working Group scoring was used to assess posterior inflammation in FA images [18]. To minimize errors, FA scores were evaluated by two specialists (TTY and YSZ). In the case of a dispute, the final decision was made by the senior specialist SWR.
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IMT reduction and GC-sparing effects: A corticosteroid-sparing effect was defined as complete withdrawal from systemic corticosteroid therapy while maintaining clinical stability.
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Systemic disorder: Routine blood examinations and liver and renal function tests were performed every 2 months.
Statistical Analysis
Results
Patient Characteristics Before Treatment Initiation
Demographics | CT (n = 21) | ADA (n = 48) | p value |
---|---|---|---|
Age at diagnosis of uveitis, mean ± SD | 12.76 ± 3.73 | 11.08 ± 3.32 | 0.085 |
Age at initial treatment, mean ± SD | 13.00 ± 3.69 | 12.23 ± 3.37 | 0.398 |
Female gender, n (%) | 16 (76.2) | 29 (60.4) | 0.206 |
Diopters (D), mean ± SD | − 0.80 ± 3.58 | − 0.45 ± 1.20 | 0.545 |
Time (month), mean ± SD | |||
Uveitis history before initial treatment | 5.55 ± 8.07 | 12.57 ± 16.46 | 0.074 |
Follow-up after initial treatment | 24.56 ± 12.48 | 25.64 ± 8.57 | 0.677 |
No previous treatment, n (%) | 6 (28.6) | 8 (16.7) | 0.332 |
Anatomic type of uveitis, n (%) | 1.000 | ||
Posterior uveitis | 4 (19.0) | 8 (16.7) | |
Panuveitis | 17 (81.0) | 40 (83.3) | |
Uveitides, n (%) | 0.503 | ||
BD | 14 (66.7) | 24 (50.0) | |
NIU | 6 (28.6) | 20 (41.7) | |
VKH | 1 (4.8) | 4 (8.3) |
CT (n = 42) | ADA (n = 96) | p value | |
---|---|---|---|
BCVA (LogMAR), mean ± SD | 0.50 ± 0.45 | 0.53 ± 0.47 | 0.697 |
Anterior chamber cells, n (%) | |||
≤ 0.5 | 15 (35.7) | 18 (18.8) | 0.032* |
1 | 14 (33.3) | 29 (30.2) | 0.715 |
2 | 7 (16.7) | 41 (42.7) | 0.003* |
3 | 10 (23.8) | 20 (20.8) | 0.697 |
4 | 0 (0.0) | 4 (4.2) | 0.314 |
Vitreous cells, n (%) | |||
≤ 0.5 | 6 (15.8) | 3 (3.2) | 0.027* |
1 | 17 (44.7) | 42 (44.7) | 0.995 |
2 | 10 (26.3) | 30 (31.9) | 0.526 |
3 | 4 (19.0) | 17 (18.1) | 0.282 |
4 | 1 (2.6) | 2 (2.1) | 1.000 |
CMT, median [IQR] µm | 240 (210, 625) | 220 (200, 288) | 0.102 |
FA score, median [IQR] | 17.23 ± 6.59 | 15.64 ± 6.30 | 0.276 |
Ophthalmic complications, n (%) | |||
Central band keratopathy | 3 (7.1) | 6 (6.3) | 1.000 |
Synechia | 4 (15.4) | 22 (22.9) | 0.064 |
Cataract | 9 (21.4) | 27 (28.1) | 0.410 |
Macular edema | 12 (28.6) | 19 (19.8) | 0.255 |
CT (n = 21) | ADA (n = 48) | p value | |
---|---|---|---|
Initial GCs, median [IQR] mg qd | 40 (21, 60) | 55 (21.3, 60) | 0.935 |
Initial IMTs strategy, n (%) | |||
GCs + MTX | 11 (52.4) | 15 (31.3) | 0.096 |
GCs + MTX + CSA | 7 (33.3) | 26 (54.2) | 0.111 |
GCs + MMF | 3 (14.3) | 7 (14.6) | 1.000 |
Change dosage of IMTs, mean ± SD | |||
GCs, mg qd | − 30.0 (− 57.5, − 13.5) | − 50.0 (− 60.0, − 20.0) | 0.397 |
MTX, mg qw | 0.0 (− 1.25, 11.25) | − 7.5 (− 10.0, − 0.63) | 0.000* |
CSA, mg bid | 0.0 (0.0, 50.0) | − 50.0 (− 75.0, − 25.0) | 0.000* |
MMF, g bid | 0.25 (0.0, 0.50) | 0.0 (0.0, 0.25) | 0.022* |
GCs-free at final visit, n (%)a | 6 (30.0) | 25 (55.6) | 0.102 |
Discontinuation of main regiment, n (%)b | 16 (76.2) | 19 (39.6) | 0.005* |
Recurrent inflammation | 7 (33.3) | 9 (18.8) | 0.187 |
Adverse events | 6 (28.6) | 1 (2.1) | 0.000* |
Remission | 2 (9.5) | 8 (16.7) | 0.438 |
Patient request | 1 (4.8) | 1 (2.1) | 0.542 |
Other treatments, n (%) | |||
Peribulbar injection | 4 (19.0) | 8 (16.7) | 1.000 |
Intraocular injection | 0 (0.0) | 3 (6.3) | 0.548 |
Laser peripheral iridotomy | 1 (4.8) | 1 (2.1) | 0.519 |
Abnormal blood test, n (%) | 7 (33.3) | 15 (31.3) | 0.864 |
Adverse events, n (%) | 7 (33.3) | 16 (33.3) | 1.000 |
Nausea/vomiting | 2 (9.5) | 4 (8.3) | |
Rash/eczema | 1 (4.8) | 3 (6.3) | |
Acne | 3 (14.3) | 0 (0.0) | |
Weight change | 3 (14.3) | 1 (2.1) | |
Cough/cold | 2 (9.5) | 6 (12.5) | |
Restlessness | 3 (14.3) | 0 (0.0) | |
Fatigue | 0 (0.0) | 3 (6.3) | |
Growth retardation | 0 (0.0) | 2 (4.2) |
Improvement of Primary Outcomes
CT (n = 42) | ADA (n = 96) | p value | |
---|---|---|---|
BCVA (LogMAR) change, mean ± SD | − 0.0097 ± 0.47 | − 0.30 ± 0.47 | 0.001* |
Alleviation of anterior chamber cells, n (%) | 12 (44.4) | 69 (88.5) | 0.000* |
Alleviation of vitreous cells, n (%) | 14 (43.8) | 85 (92.4) | 0.000* |
Change of FA score, mean ± SD | − 7.09 ± 8.21 | − 12.23 + 5.88 | 0.002* |
Change of CMT, median [IQR] µm | − 6.0 (− 320, 0) | − 6 (− 88, 0) | 0.291 |
Reduction number of eyes with macular edema, n (%)a | 10 (76.9) | 19 (100.0) | 0.058 |
Treatment response | |||
Alleviation population during follow-up, n (%) | 38 (90.5) | 100 (100.0) | 0.008* |
First alleviation time, median (range) | 2.30 ± 0.46 | 1.03 ± 0.12 | 0.002* |
Alleviation in 3 months, n (%) | 26 (61.9) | 87 (90.6) | 0.000* |
Relapse | |||
First relapse time after alleviation, median [IQR] month | 3.20 (1.43, 7.08) | 9.70 (4.30, 14.50) | 0.001* |
Relapse times of each eye, median (range) | 3 (0–9) | 1 (0–4) | 0.000* |
Frequency of ocular relapses, median [IQR] times/yearb | 1.36 (0.87, 2.58) | 0.71 (0.49, 1.14) | 0.000* |
No relapse eyes, n (%)b | 4 (10.5) | 46 (47.9) | 0.000* |