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OBJECTIVES: The incidence of anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) shows disparate results due to variable classification criteria and heterogeneous-population series. We aimed to estimate the incidence of AAV in a well-defined population with standardized classification criteria. METHODS: Population-based study of AAV patients diagnosed from January 2000 to December 2023 in Cantabria, Northern Spain. Patients were classified according to ACR/EULAR 2022 into granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or unclassified vasculitis if the criteria were not met. Eosinophilic granulomatosis with polyangiitis (EGPA) patients were not included. The annual incidence rates were estimated by cases over 1,000 000 (106) (95% CI) including overall AVV, type of AAV, sex, and year of diagnosis. A literature review was also performed. RESULTS: We included 152 (80/72 men; mean age; 70.6 ± 13.18 years) patients. They were classified as MPA (67; 44%), GPA (64; 42.2%), and unclassified vasculitis (21; 13.8%). Annual incidence was 13.4 (10-16.8)/106 [male 14.5 (10.5-18.5); female 12.1 (8.7-15.6)]. The Annual incidence of MPA was 5.9 (4-7.8)/106 and GPA 5.6 (3.9-7.3)/106. The mean Annual incidence increased from 6.1 (4.5-7.7)/106-16.5 (5.6-27.4)/106 in the last three years, particularly, in GPA from 2.3 (0.3-4.9)/106-8.2 (2-14.5)/106. The prevalence of AAV was 184.7 (181-188)/106. CONCLUSION: During a 20-year period we found that the incidence of AAV (GPA and MPA) in Northern Spain is higher than Southern Spain, but lower than Northern European countries. An increase in the incidence was observed in the last years.
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ANCA-associated vasculitis (AAV) comprises a group of necrotizing vasculitis that mainly affects small- and medium-sized vessels. Serum anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (anti-MPO) and anti-proteinase 3 (anti-PR3), levels may correlate to severity, prognosis, and recurrence of the disease. A retrospective analysis of 101 patients with MPO-positive and 54 PR3-positive vasculitis was performed, using laboratory established cut-off value, measured by chemiluminescence. Furthermore, data of renal disease and pulmonary involvement were collected at vasculitis diagnosis, as well as the progress, requiring dialysis, transplant, or mortality. For anti-MPO antibodies with a diagnosis of vasculitis (n = 77), an area under the curve (AUC) was calculated (AUC = 0.8084), and a cut-off point of 41.5 IU/ml was determined. There were significant differences in anti-MPO levels between patients with renal or pulmonary dysfunction (n = 65) versus those without them (n = 36) (p = 0.0003), and a cut-off threshold of 60 IU/ml was established. For anti-PR3 antibodies with a diagnosis of vasculitis (n = 44), an area under the curve (AUC) was calculated (AUC = 0.7318), and a cut-off point of 20.5 IU/ml was determined. Significant differences in anti-PR3 levels were observed between those patients with renal or pulmonary dysfunction (n = 30) and those without them (n = 24) (p = 0.0048), and a cut-off threshold of 41.5 IU/ml was established. No significant differences between those patients who had a worse disease progression and those who did not were found for anti-MPO and anti-PR3. Anti-MPO and anti-PR3 levels at the moment of vasculitis diagnosis are related with disease severity but not with disease outcome or vasculitis recurrence.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Luminescência , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Mieloblastina , PeroxidaseRESUMO
INTRODUCTION: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) includes three heterogeneous and difficult to treat clinical entities. Intravenous immunoglobulins (IVIG) may constitute a good therapeutic option, although data hitherto are scarce. The aim of this study was to assess the effectiveness and safety of IVIG in AAV in a real-world setting. METHODS: Single center observational study of patients with AAV with at least one cycle of IVIG since January of 2000 to December of 2020. AAV diagnosis was based on a compatible clinical presentation and positive ANCA serology and/or compatible histology. Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). The effectiveness was evaluated by clinical and laboratory parameters (CRP, ESR) and its glucocorticoid-sparing effect. These variables were measured at one, six, twelve and twenty-four months of IVIG treatment. The doses of IVIG were 2g/kg in the following cycles of administration: 1 g/kg/day in 2 days (n=12); 0.5 g/kg/day in 4 days (n=11); 0.4 g/kg/day in 5 days (n=5). The clinical improvement was classified according to BVAS categories in remission, partial response and no response. RESULTS: Twenty-eight patients (15 granulomatosis-polyangiitis, 10 microscopic polyangiitis and 3 eosinophilic granulomatosis with polyangiitis) were included. Reasons for using IVIG were relapse/refractory disease (n=25), active or suspected infection (n=3), and both (n=5). We observed a rapid and maintained BVAS score improvement, increasing from 34.6% at 1 month to 56.5% at 2 years of follow-up (p=0.12), and a reduction of glucocorticoids dose. Therapy was well tolerated and adverse events mild and scarce. CONCLUSION: IVIG represents an effective and relative safe therapeutic alternative in relapsing/refractory AAV or in presence of a concomitant active infection.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Imunoglobulinas Intravenosas/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnósticoRESUMO
BACKGROUND/PURPOSE: The manifestations of uveitis are well established in axial spondyloarthritis (ax-SpA), but not in psoriatic arthritis (PsA). We aimed to assess, in a large unselected series of PsA: (A) the frequency and clinical features of uveitis; (B) its association with PsA activity, the impact of disease and functional disability, and (C) its relationship with the biological treatment. In addition, a literature review was performed. METHODS: Retrospective longitudinal study of PsA patients from a single referral hospital. PsA was classified according to the CASPAR criteria, and uveitis was diagnosed by experienced ophthalmologists. RESULTS: We studied 406 patients with PsA (46.3±12.3 years). Uveitis was observed in 20 (4.9%). Uveitis was acute in all cases, anterior (80%), unilateral (80%) and recurrent (50%). Patients with uveitis had a higher prevalence of HLA-B27 (45% vs 7.5%, p<0.0001), sacroiliitis on MRI (25% vs 8.3% p=0.027), ocular surface pathology (10% vs 0.8%, p=0.021), and median PsA impact of Disease Score (5.9 (2.1-6.8) vs 1.25 (0.0-3.0), p=0.001) and Bath Ankylosing Spondylitis Functional Index (4 (1.6-5) vs 1.0 (0.0-3.5), p=0.01) than patients without uveitis.The exposure adjusted incidence rate (episodes/100 patients-year) of uveitis before versus after biological treatment decreased with anti-TNFα monoclonal antibodies (56.3 vs 9.4) and increased with etanercept (ETN) (6.03 vs 24.2) and secukinumab (SECU) (0 vs 50) (including only one patient treated in the last two cases). CONCLUSION: The prevalence of uveitis in patients with PsA was about 5%. The pattern was similar to that observed in ax-SpA. Uveitis was associated with a worse quality of life and greater functional disability. The uveitis exposure adjusted incidence rate decreased with anti-TNFα monoclonal antibodies and increased with ETN and SECU.
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Artrite Psoriásica , Uveíte , Humanos , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Qualidade de Vida , Estudos Longitudinais , Estudos Retrospectivos , Universidades , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/epidemiologia , Etanercepte/uso terapêuticoRESUMO
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.
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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
OBJECTIVES: To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA). METHODS: This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection. RESULTS: 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients. CONCLUSION: Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.
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Antirreumáticos , Aterosclerose , Espondiloartrite Axial , Espondiloartrite Axial não Radiográfica , Espondilartrite , Espondilite Anquilosante , Antirreumáticos/uso terapêutico , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos Transversais , Humanos , Prednisona/uso terapêutico , Espondilartrite/complicações , Espondilartrite/diagnóstico por imagem , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico por imagemRESUMO
The natural history of antiphospholipid antibodies (aPL) carriers is not well-established. The objectives of the present study were (a) to study the probability of developing clinical criteria of antiphospholipid syndrome (APS), (b) to identify potential risk factors for developing thrombosis and/or obstetric complications, (c) to study the association between the antibody profile and development of APS, and (d) to determine the efficacy of primary prophylaxis. We retrospectively analyzed 138 subjects with positive aPL who did not fulfill clinical criteria for APS. The mean follow-up time was 138 ± 63.0 months. Thirteen patients (9.4%) developed thrombosis after an average period of 73.0 ± 48.0 months. Independent risk factors for thrombosis were smoking, hypertension, thrombocytopenia, and triple aPL positivity. Low-dose acetyl salicylic acid did not prevent thrombotic events. A total of 28 obstetric complications were detected in 92 pregnancies. During the follow-up, only two women developed obstetric APS. Prophylactic treatment in pregnant women was associated with a better outcome in the prevention of early abortions. The thrombosis rate in patients with positive aPL who do not meet diagnostic criteria for APS is 0.82/100 patients-year. Smoking, hypertension, thrombocytopenia, and the aPL profile are independent risk factors for the development of thrombosis in aPL carriers. Although the incidence of obstetric complications in this population is high (31.6%), only a few of them meet APS criteria. In these women, prophylactic treatment might be effective in preventing early abortions.
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Síndrome Antifosfolipídica , Hipertensão , Trombocitopenia , Trombose , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Gravidez , Estudos Retrospectivos , Fatores de Risco , Trombose/epidemiologia , Trombose/etiologiaRESUMO
OBJECTIVES: Rapid control of intraocular inflammation in non-infectious uveitis (NIU) is mandatory to avoid irreversible structural and functional damage. In this study, we assessed the efficacy and safety of intravenous methylprednisolone (IVMP) pulses in the treatment of NIU. METHODS: A retrospective case series of 112 patients who received IVMP for the treatment of NIU, either isolated or associated with different underlying diseases, was studied. Intraocular inflammation (anterior chamber cells and vitritis) was the primary outcome measure. Secondary outcome measures were macular thickness and best corrected visual acuity (BCVA). Patients were assessed at baseline visit, and at days 2-5, 7, 15 and 30 after initiation of IVMP pulse therapy. RESULTS: A total of 112 patients (mean age 42±14.5 yrs) were assessed. An underlying immune-mediated disease was diagnosed in 73 patients. Inflammatory ocular patterns were panuveitis (n=68), posterior uveitis (n=30), anterior uveitis (AU) (n=12), and intermediate uveitis (n=2). Additionally, patients presented cystoid macular oedema (CME) (n=50), retinal vasculitis (n=37), and exudative retinal detachment (n=31). Therapies used before IVMP included intraocular glucocorticoids (n=4), high-dose oral systemic glucocorticoids (n=77), and conventional (n=107) or biologic (n=40) immunosuppressive drugs. IVMP dose ranged from 80 to 1,000 mg/day for 3-5 consecutive days. Improvement was observed in AU, vitritis, BCVA, CME, and retinal vasculitis. At first month evaluation, total remission was achieved in 19 patients. Side effects of IVMP were respiratory infections (n=3), uncontrolled hyperglycaemia (n=1), herpes zoster (n=1), and oral candidiasis (n=1). CONCLUSIONS: IVMP pulse therapy was effective and safe, and achieved rapid control of NIU.
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Metilprednisolona , Uveíte , Adulto , Glucocorticoides/efeitos adversos , Humanos , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Acuidade VisualRESUMO
OBJECTIVES: Clinicians often face the challenge of providing effective and safe therapy for pregnant women with uveitis. Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer. In this study we assessed the efficacy of CZP in pregnant women with uveitis. We also provided information on outcomes of pregnant women and neonates exposed to CZP. METHODS: We carried out a multicentre study of women with uveitis who received CZP during pregnancy and their neonates. The main visual outcomes were visual acuity (VA), intraocular inflammation and corticosteroid-sparing effect. Pregnancy outcomes, maternal and neonatal infections and congenital malformations were also assessed. RESULTS: We studied 14 women (23 affected eyes); mean age of 34.3±5.5 years. The underlying diseases were spondyloarthritis (n=7), idiopathic (n=2), and Vogt-Koyanagi-Harada, rheumatoid arthritis, juvenile idiopathic arthritis, punctate inner choroidopathy and Behçet's disease (1 each). The patterns of ocular involvement were anterior (n=10), posterior (n=2), intermediate (n=1), panuveitis (n=1). Cystoid macular oedema was present in one patient (1 eye). Uveitis was bilateral in nine cases and chronic in seven patients. CZP was started before getting pregnant in ten patients and after conceiving in four. All patients achieved or maintained ocular remission throughout pregnancy. Fifteen healthy infants were born. Only one woman presented a mild infection during pregnancy. Neither infections nor malformations were observed in neonates after a follow-up of 6 months. Six infants were breastfed and all of them received scheduled vaccinations without complications. CONCLUSIONS: Certolizumab pegol is effective and safe in women with uveitis during pregnancy.
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Gestantes , Uveíte , Adulto , Terapia Biológica , Certolizumab Pegol/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Lactente , Recém-Nascido , Gravidez , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/tratamento farmacológicoRESUMO
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.
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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: We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). DESIGN: Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. SUBJECTS: We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behçet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. METHODS: Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. MAIN OUTCOME MEASURES: Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. RESULTS: The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. CONCLUSIONS: Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.
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Fatores Biológicos/administração & dosagem , Úlcera da Córnea/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores Biológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
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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
PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.
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Adalimumab/administração & dosagem , Síndrome de Behçet/complicações , Uveíte/tratamento farmacológico , Acuidade Visual , Adulto , Anti-Inflamatórios/administração & dosagem , Síndrome de Behçet/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Imunossupressores/uso terapêutico , Masculino , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/etiologiaRESUMO
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 golimumab (GLM), a fully humanised anti-TNF-α monoclonal antibody, in refractory juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: This was a multicentre study of JIA-associated uveitis refractory to standard synthetic immunosuppressive drugs and in most cases to other anti-TNF-α agents. Results were expressed as mean±standard deviation or as median (range or interquartile range). The Wilcoxon signed-rank test was used to compare continuous variables. A literature review of the efficacy of GLM in uveitis related to JIA was also conducted. RESULTS: We studied 7 patients (5 females; mean age 21.7±7.5 years; 13 affected eyes). Uveitis was bilateral in 6. Cystoid macular oedema (CME) occurred in 3 patients (5 eyes). Besides corticosteroids and synthetic immunosuppressive drugs, patients had received before GLM a median of 2 biologic agents (range 0-3) including adalimumab (n=6), etanercept (n=2), infliximab (n=3) and abatacept (n=2). GLM dose was 50 mg/sc every 4 weeks. After 6 months of therapy the number of anterior chamber cells decreased from 1 [0.25-1.5] to 0 [0-0.5] (p=0.02) and optical coherence tomography (in patients with CME) from 313.6±77.05 to 261.4±75.1 µm (p=0.03). The best-corrected visual acuity increased from 0.5 to 0.62 (p=0.018). Complete remission of uveitis was achieved in 4 of 7 patients after 16.8±11.4 months of follow-up. However, 2 of the seven patients had to be switched to tocilizumab due to inefficacy. Local erythema at the injection site was observed in 2. CONCLUSIONS: GLM may be considered in the management of refractory JIA-related uveitis.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Juvenil/complicações , Uveíte/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Tomografia de Coerência Óptica , Uveíte/fisiopatologia , Acuidade VisualRESUMO
PURPOSE: To evaluate tocilizumab (TCZ) efficacy in severe and refractory birdshot chorioretinopathy (BSCR). METHODS: Assessment of BSCR patients refractory to conventional immunosuppressive and anti-TNF-α drugs who underwent TCZ therapy. RESULTS: Two HLA-A29 positive patients (man/37 years and woman/38 years; four affected eyes) with BSCR were studied. They had a chronic bilateral posterior uveitis. Patient 1 had been treated with intraocular and oral corticosteroids, cyclosporine A, and infliximab whereas Patient 2 received intravenous methylprednisolone pulses, cyclosporine A, azathioprine, and adalimumab. At TCZ onset they had macular edema (four eyes); visual acuity (VA) impairment (four eyes); vitritis (one eye); and diffuse angiographic signs of vasculitis (periphlebitis) (two eyes). Improvement of VA and OCT was observed following TCZ therapy in both patients. After a follow-up of 18 months (Patient 1) and 10 months (Patient 2), respectively, a corticosteroid sparing effect without any adverse effects was achieved in both cases. CONCLUSIONS: TCZ was effective in two patients with BSCR refractory to anti-TNF-α agents.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Coriorretinite/tratamento farmacológico , Edema Macular/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Adulto , Coriorretinopatia de Birdshot , Coriorretinite/diagnóstico , Coriorretinite/fisiopatologia , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Edema Macular/diagnóstico , Edema Macular/fisiopatologia , Masculino , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Acuidade Visual/fisiologiaRESUMO
OBJECTIVE: To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. RESULTS: We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 µm to 259.1 ± 39.5 µm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient. CONCLUSION: TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Juvenil/complicações , Receptores de Interleucina-6/antagonistas & inibidores , Uveíte/tratamento farmacológico , Uveíte/etiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
OBJECTIVES: To determine if cutaneous vasculitis (CV) associated with severe infection has some histopathologic findings that may help us to differentiate patients with this condition from other patients with CV. METHODS: We reviewed the skin biopsy specimens of patients with leukocytoclastic CV associated with a severe bacterial infection. Histopathologic findings of these patients were compared with those observed in leukocytoclastic CV secondary to other causes. Biopsy-proven leukocytoclastic CV were stratified as follows: group a): CV associated with severe underlying bacterial infection; group b): CV without severe bacterial infection but with systemic involvement; group c): CV without systemic involvement. Slides were reviewed by expert pathologists that were blind to the clinical information. The severity of vascular lesions was measured according to a semiquantitative scale (Hodge index). A comparative study between group a) and the other groups was conducted. RESULTS: group a) included 12 patients (2 women/10 men), mean age± SD 56±15 years; group b) 21 patients (10 women/11 men), 52±18 years; and group c) 19 patients (12 women/7 men), 59±24 years. Presence of neutrophilia was significantly increased in biopsies from group a) when compared with the other two groups. Also, a trend to higher frequency of pustular dermatosis was found in patients from group a). Hodge index, degree of inflammatory infiltrate and deep arterioles involvement were similar in all groups. CONCLUSIONS: Neutrophilia is common in skin biopsies of patients with CV associated with severe bacterial infection. No other histopathological findings help us to establish the presence of a severe underlying infection.
Assuntos
Infecções Bacterianas/complicações , Dermatopatias Vasculares/patologia , Vasculite/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dermatopatias Vasculares/etiologia , Vasculite/etiologiaRESUMO
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
OBJECTIVES: To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. METHODS: Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. RESULTS: A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range-IQR) 0.5 (0-2) versus 0 (0-0) (p = 0.003), vitritis 0 (0-1.25) versus 0 (0-0) (p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) (p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0-30)mg at the onset of the anti-TNF-α therapy to 0 (0-0)mg at 2 years (p = 0.02). Significant reduction was also achieved in the immunosuppressive load. CONCLUSION: Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.