TCZ could be a therapeutic option in patients with BD and refractory uveitis.

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or inefficacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.

Objective. To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD).Methods.We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups.Results. The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042).Conclusion. Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up. 9 Manuel Díaz-Llopis, MD, PhD, ATIENZA-MATEOETAL | PATIENTS AND METHODS Study design, enrollment criteria, and definitions.We conducted an observational, open-label multicenter study including 177 patients with refractory uveitis due to BD who were treated with IFX or ADA as first-line biologic therapy. The dosing schedule was as follows: for IFX, 3-5 mg/kg intravenously (IV) at

Objective In a large series of Caucasian patients with refractory uveitis due to Behçet disease (BD) treated with infliximab (IFX) we assessed: a) long-term efficacy and safety and b) IFX optimization when ocular remission was achieved. Methods Multicenter study of IFX-treated patients with BD uveitis refractory to conventional immunosuppressant agents.103 patients/185 affected eyes were treated with IFX as first biologic therapy as follows: 3-5 mg/kg i.v. at 0, 2, 6 and then every 4-8 weeks. a) The main outcome variables were analyzed at baseline, 1st week, 1st and 6th months and 1st and 2nd years of IFX therapy. b) After remission, based on a shared decision between patient and clinician, IFX optimization was performed. Efficacy, safety, and cost of IFX therapy were evaluated. Results In whole series (n=103), main outcome variables showed a rapid and maintained improvement, reaching remission in 78 patients after a mean IFX duration of 31.5 months. Serious adverse events were observed in 9 patients: infusional reactions (n=4), tuberculosis (n=1), Mycobacterium avium pneumonia (n=1), severe oral ulcers (n=1), palmoplantar psoriasis (n=1) and colon carcinoma (n=1). In the optimization subanalysis, the comparative study between optimized and nonoptimized groups showed: a) no differences in clinical characteristics at baseline; b) similar maintained improvement in most ocular outcomes; and c) lower severe adverse events, and d) lower mean IFX costs in optimized group (4,826.52 vs. 9,854.13 euros/patient/year). Conclusion IFX seems to be effective and relatively safe in Caucasian patients with refractory BD uveitis. IFX optimization is effective, safe, and cost-effective.

for the Biotherapies in Uveitis (BioÚvea) Study Group* Purpose: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting.Design: Multicentric, nationwide, registry-based, ambispective, observational study.Participants: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017.Methods: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The DRR and drug retention time (DRT) were estimated using the KaplaneMeier method. Median follow-up was analyzed by reverse KaplaneMeier. 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.Main Outcome Measures: Drug retention rate and DRT. Results: 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 (0.97e131.67) 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 ¼ 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.Conclusions: 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. Ophthalmology 2020;127:814-825 ª 2019 by the American Academy of Ophthalmology Supplemental material available at www.aaojournal.org.Noninfectious uveitis (NIU) is composed of a large group of diseases that involve the inflammation of the intraocular tissues. 1 Approximately 20% of legal blindness has been attributed to NIU in developed countries. 2,3 The disease usually affects the working-age population, leading to a significant impact on patients' quality of life and welfare. 4,...

ObjectivesTo assess the efficacy of Tocilizumab (TCZ) in refractory thyroid associated orbitopathy (TAO) due to Grave’s disease.MethodsMulticenter study of 29 patients with TAO refractory to conventional immunosuppressive therapy.ResultsWe studied 29 patients (58 eyes) (23 women/6 men); mean age at diagnosis 48.79±12.39 years. Besides oral corticosteroids and before the onset of TCZ, patients had been treated with pulses of intravenous methylprednisolone (n=24), methotrexate (n=2) and other drugs (methimazole in 4 cases, leflunomide in 1, selenium in 9). Urgent decompressive surgery had to be performed in 2 patients.According to the classification of severity of the EUGOGO group (European Group on Graves’ Orbitopathy) using the clinical activity score (CAS), before TCZ onset patients whose data were available had severe (n=14 eyes) or moderate (n=22 eyes) disease. Moreover, patients presented exophthalmos (n=30 eyes), strabismus (n=17 eyes), muscle fibrosis (n=15 eyes) and dysthyroid optic neuropathy (n=1).TCZ was used in monotherapy (n=27) or combined with methotrexate (n=2) at 8 mg/kg/iv/4 weeks (n=24) or 162 mg/sc/week (n=5). TCZ yielded rapid and maintained improvement in all ocular parameters (TABLE).After a mean follow-up of 8.96±7.55 months using TCZ, all patients experienced ocular improvement, with TCZ withdrawal in 16 cases due to complete remission (n=5) or stability of ocular inflammation (n=11). Only 4 adverse effects were observed (neutropenia, external otitis, otitis media, costal osteitis).TABLE. Improvement of ocular parameters with TCZ therapy. Data are expressed as mean±SD or median[IQR].BASAL1 WEEK2 WEEKS1 MONTH3 MONTHS6 MONTHS1 YEAR VA0.7 [0.5–1]0.7 [0.6–1]0.8 [0.7–1]0.85 [0.7–1]1 [0.9–1]1 [0.7–1]1 [0.8–1]IOP19.22±4.2017.25±1.9016.75±2.3118.23±5.0017.39±3.5116.52±3.5616.00±3.41CAS4.97±1.724.85±2.95-3.40±2.282.34±1.711.29±1.121.11±0.85VA=visual acuity; IOP=intraocular pressure; CAS=clinical activity score (0/7 at baseline, 0/10 in the rest of time measures).ConclusionsTCZ appears to be useful in TAO treatment.Reference[1] Bartalena L, Baldeschi L, Dickinson AJ, et al. Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid2008;18(3):333–346.Disclosure of InterestNone declared

No abstract

Introduction: Uveitis is the inflammation of the middle layer of the eye, the uvea, and is a major cause of blindness. None of the instruments used in clinical practice are, in themselves, sufficient to evaluate the course of uveitis. Therefore, it is necessary to develop instruments enabling standardized measurement of inflammatory activity. We developed a