RESUMO
OBJECTIVE: To develop evidence-based expert-consensus recommendations for the management of non-infectious, non-neoplastic, non-demyelinating disease associated uveitis. METHODS: Clinical research questions relevant to the objective of the document were identified, and reformulated into PICO format (patient, intervention, comparison, outcome) by a panel of experts selected based on their experience in the field. A systematic review of the available evidence was conducted, and evidence was graded according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Subsequently, recommendations were developed. RESULTS: Three PICO questions were constructed referring to uveitis anterior, non-anterior and complicated with macular edema. A total of 19 recommendations were formulated, based on the evidence found and/or expert consensus. CONCLUSIONS: Here we present the first official recommendations of the Spanish Society of Rheumatology for the treatment of non-infectious and non-demyelinating disease associated uveitis. They can be directly applied to the Spanish healthcare system as a tool for assistance and therapeutic homogenisation.
Assuntos
Edema Macular , Uveíte , Humanos , Edema Macular/complicações , Uveíte/complicações , Uveíte/terapia , Revisões Sistemáticas como Assunto , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: To compare the efficacy of TNF inhibitors (adalimumab (ADA) and infliximab (IFX)) vs tocilizumab (TCZ) in patients with refractory cystoid macular edema (CME) due to Behçet's disease (BD). METHODS: Multicenter study of patients with BD-associated CME refractory to conventional and/or biological immunosuppressive drugs. From a cohort of 177 patients treated with anti-TNF and 14 patients treated with TCZ, we selected those with CME at baseline. We analyzed the evolution of macular thickness (main outcome), best-corrected visual acuity (BCVA) and intraocular inflammation (Tyndall and vitritis) from baseline up to 4 years in the 3 groups mentioned. RESULTS: 49 patients and 72 eyes with CME were included. ADA was used in 25 patients (40 eyes), IFX in 15 (21 eyes) and TCZ in 9 (11 eyes). No statistically significant baseline differences were observed between the 3 groups except for a lower basal BCVA in TCZ group and a higher basal degree of intraocular inflammation in ADA group. Most patients from all groups had received several conventional immunosuppressive drugs. In addition, most patients in the group of TCZ had also received anti-TNF agents. Biological therapy was used in monotherapy (n=8) or combined with conventional immunosuppressive drugs (n=41). Macular thickness progressively decreased in the 3 groups, with no signs of CME after 1 year of treatment. Similarly, BCVA improvement and inflammatory intraocular remission was achieved in all groups. CONCLUSION: Refractory CME associated with BD uveitis can be effectively treated either with ADA, IFX or TCZ. Furthermore, TCZ is effective in patients resistant to anti-TNF therapy.
Assuntos
Síndrome de Behçet , Produtos Biológicos , Edema Macular , Uveíte , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/diagnóstico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Edema Macular/etiologia , Edema Macular/complicações , Resultado do Tratamento , Uveíte/complicações , Uveíte/tratamento farmacológico , Adalimumab/uso terapêutico , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Inflamação/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Estudos Retrospectivos , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVE: In a large series of White patients with refractory uveitis due to Behçet disease (BD) being treated with infliximab (IFX), we assessed (1) long-term efficacy and safety of IFX, and (2) IFX optimization when ocular remission was achieved. METHODS: Our multicenter study of IFX-treated patients with BD uveitis refractory to conventional immunosuppressant agents treated 103 patients/185 affected eyes with IFX as first biologic therapy in the following intervals: 3-5 mg/kg intravenous at 0, 2, 6, and then every 4-8 weeks. The main outcome variables were analyzed at baseline, first week, first month, sixth month, first year, and second year of IFX therapy. 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 the 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: infusion 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 (1) no differences in clinical characteristics at baseline, (2) similar maintained improvement in most ocular outcomes, (3) lower severe adverse events, and (4) lower mean IFX costs in the optimized group (4826.52 vs 9854.13 per patient/yr). CONCLUSION: IFX seems to be effective and relatively safe in White patients with refractory BD uveitis. IFX optimization is effective, safe, and cost-effective.
Assuntos
Síndrome de Behçet , Uveíte , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Seguimentos , Humanos , Infliximab/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Uveíte/tratamento farmacológico , Uveíte/etiologiaRESUMO
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 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. 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 (0.97-131.67) 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. 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.
Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Uveíte/tratamento farmacológico , Adalimumab/efeitos adversos , Adulto , Anti-Inflamatórios/efeitos adversos , Terapia Biológica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Espanha , Uveíte/diagnóstico , Uveíte/fisiopatologia , Suspensão de Tratamento , Adulto JovemRESUMO
PURPOSE: To assess the correlation between clinical cataract surgery indication and the objective scatter index (OSI) by defining the optimal OSI cutoff point in the surgery scheduling. SETTING: Ophthalmology service, Consorcio Hospital General Universitario, Valencia, Spain. DESIGN: Prospective triple-masked randomized single-center study. METHODS: Patients with cataractous eyes were recruited, and those with anterior segment disease, abnormal posterior pole, and/or previous ocular surgery were excluded. The principle of double-pass aberrometry was used by the main investigator to determine an OSI, after measuring subjective refraction and corrected distance visual acuity (CDVA), and then slitlamp evaluation was carried out by an independent researcher. The surgical decision was based on the current protocol according to the European guidelines. Correlation between the surgical decision, CDVA, and OSI were analyzed and an OSI discriminative value was calculated, implementing a receiver operating characteristic (ROC) curve. RESULTS: The study comprised 106 eyes (73 patients). The analysis established an inverse linear correlation between OSI and CDVA (r = -0.455, P < .0001). The comparison of the mean OSI between the surgical group (7.05 ± 4.65 [SD]) and the nonsurgical group (2.92 ± 1.88), revealed statistically significant differences (P = 5.04 × 10-9). The OSI score 3.2 was determined as the optimal cutoff value to discriminate surgical treatment (sensitivity 80%, specificity 84%). CONCLUSIONS: An optimal OSI value, according to an ROC curve calculation, was capable of providing clinicians with a powerful criterion for preoperative decision-making, thus suggesting an end to the subjectivity implicit in the cataract surgery decision-making process.
Assuntos
Catarata/congênito , Cristalino/fisiopatologia , Refração Ocular/fisiologia , Espalhamento de Radiação , Acuidade Visual/fisiologia , Aberrometria , Idoso , Idoso de 80 Anos ou mais , Catarata/diagnóstico , Catarata/fisiopatologia , Tomada de Decisões , Método Duplo-Cego , Feminino , Humanos , Implante de Lente Intraocular , Luz , Masculino , Pessoa de Meia-Idade , Facoemulsificação , Período Pré-Operatório , Estudos Prospectivos , Curva ROCRESUMO
PURPOSE: Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME. DESIGN: Retrospective case series. METHODS: Patients with CME secondary to noninfectious uveitis who had inadequate response to corticosteroids and at least 1 conventional immunosuppressive drug, and in most cases to other biological agents, were studied. CME was defined as central retinal thickness greater than 300 µm. The primary outcome measure was macular thickness. Intraocular inflammation, best-corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed. RESULTS: A total of 25 patients (mean ± standard deviation age 33.6 ± 18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n = 9), Behçet disease (n = 7), birdshot retinochoroidopathy (n = 4), idiopathic (n = 4), and sarcoidosis (n = 1). The ocular patterns were panuveitis (n = 9), anterior uveitis (n = 7), posterior uveitis (n = 5), and intermediate uveitis (n = 4). Most patients had CME in both eyes (n = 24). TCZ was used in monotherapy (n = 11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7 ± 177.2 vs 259.1 ± 499.5 µm; P = .00009) and BCVA (0.39 ± 0.31 vs 0.54 ± 0.33; P = .0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9 ± 13.6 mg/day vs 3.1 ± 2.3 mg/day; P = .002) after 12 months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow-up of 12.7 ± 8.34 months. CONCLUSION: Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Edema Macular/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Uveíte/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Juvenil/complicações , Coriorretinite/complicações , Feminino , Humanos , Imunossupressores/uso terapêutico , Infusões Intravenosas , Macula Lutea/diagnóstico por imagem , Macula Lutea/patologia , Edema Macular/diagnóstico por imagem , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoidose/complicações , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte/complicações , Uveíte/diagnóstico por imagem , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Methods: Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results: We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ could be a therapeutic option in patients with BD and refractory uveitis.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Behçet/complicações , Receptores de Interleucina-6/antagonistas & inibidores , Uveíte/tratamento farmacológico , Adolescente , Adulto , Idoso , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/etiologia , Adulto JovemRESUMO
OBJECTIVES: To assess the efficacy of other biologic therapies, different from infliximab (IFX) and adalimumab (ADA), in patients with Behçet's disease uveitis (BU). METHODS: Multicenter study of 124 patients with BU refractory to at least one standard immunosuppressive agent that required IFX or ADA therapy. Patients who had to be switched to another biologic agent due to inefficacy or intolerance to IFX or ADA or patient's decision were assessed. The main outcome measures were the degree of anterior and posterior chamber inflammation and macular thickness. RESULTS: Seven (5.6%) of 124 cases (4 women/3 men; mean age, 43 (range 28- 67) years; 12 affected eyes) were studied. Five of them had been initially treated with ADA and 2 with IFX. The other biologic agents used were golimumab (n=4), tocilizumab (n=2) and rituximab (n=1). The ocular pattern was panuveitis (n=4) or posterior uveitis (n=3). Uveitis was bilateral in 5 patients (71.4%). At baseline, anterior chamber and vitreous inflammation were present in 6 (50%) and 7 (58.3%) of the eyes. All the patients (12 eyes) had macular thickening (OCT>250µm) and 4 of them (7 eyes), cystoid macular edema (OCT>300 µm). Besides reduction anterior chamber and vitreous inflammation, we observed a reduction of OCT values, from 330.4±58.5 µm at the onset of the biological agent to 273±50 µm at month 12 (p=0.06). Six patients achieved a complete remission of uveitis. CONCLUSIONS: The vast majority of patients with BU refractory to standard immunosuppressive drugs are successfully controlled with ADA and/or IFX. Other biologic agents appear to be also useful.
Assuntos
Adalimumab/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Substituição de Medicamentos , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Uveíte/tratamento farmacológico , Adalimumab/efeitos adversos , Adulto , Idoso , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Produtos Biológicos/efeitos adversos , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores/efeitos adversos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Espanha , Fatores de Tempo , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/imunologiaRESUMO
OBJECTIVE: The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçet's disease (BD). METHODS: We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. RESULTS: Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 µm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 µm) that improved from 420 µm (s.d. 119.5) at baseline to 271 µm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. CONCLUSION: Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/tratamento farmacológico , Adalimumab , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome de Behçet/complicações , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Criança , Esquema de Medicação , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Infliximab , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Resultado do Tratamento , Uveíte/etiologia , Adulto JovemRESUMO
PURPOSE: The aim of this study was to assess the efficacy and safety of adalimumab in treating refractory autoimmune uveitis. METHODS: This work was a prospective, noncomparative, nonrandomized, clinical trial. Nineteen (19) patients meeting eligibility criteria received a 40-mg subcutaneous (s.c.) injection of adalimumab every other week during 1 year. RESULTS: All patients underwent an outcome assessment at month 12. Visual acuity improved by -0.3 logMar in 12 (31%) eyes of 38, and worsened by +0.3 logMar in 1 (2.6%) eye. All patients had an active intraocular inflammation at baseline, and 12 patients (63%) achieved control of their inflammation with adalimumab at the end of follow-up. After optic coherence tomography, 33 eyes (86%) had cystoid macular edema (CME) at baseline, and at the end of follow-up there was a complete resolution of CME in 18 of these 33 eyes (54.54%). All patients were able to reduce at least 50% of the dose of the concomitant immunosuppressive drugs at the end of follow-up. Adalimumab was well tolerated in all patients, and only local minor side effects at the s.c. injection site were observed. Nevertheless, 8 patients (42.10%) had relapses during the follow-up period that were controlled with 1 periocular steroid injection. CONCLUSIONS: Adalimumab seems to be an effective, safe therapy for the management of refractory uveitis and may provide the possibility to reduce the concomitant immunosuppressive drugs in these patients. Further long-term studies are warranted to determine the safety and efficacy of adalimumab in treating intraocular inflammation.