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1.
Arthritis Rheumatol ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237427

RESUMO

OBJECTIVE: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as first biologic drug in a large series of patients with refractory uveitis due to Behçet's disease (BD) for 1-year period. METHODS: Open-label multicenter study of IFX or ADA-treated patients with BD-uveitis refractory to conventional non-biologic treatment. IFX or ADA were chosen as first biologic treatment based on physician and patient agreement. Dosing schedule was: IFX: 3-5 mg/kg i.v. at 0, 2 and 6 weeks and every 4-8 weeks thereafter, and ADA: 40 mg/s.c./every other week without loading dose. Comparison between patients treated with IFX and patients treated with ADA was performed. RESULTS: 177 patients (316 affected eyes) were included. IFX was used in 103 and ADA in 74 cases. No significant differences at baseline were observed between IFX vs ADA groups regarding main demographic features, previous therapy and ocular severity. After one year of therapy, we observed an improvement in all ocular parameters in both groups. However, ADA therapy yielded better outcome in some parameters that in some cases yielded statistically significant differences: anterior chamber inflammation (78.18% in IFX-treated vs 92.31%in ADA-treated; p=0.06), vitritis (78.95% vs 93.33%; p=0.04), retinal vasculitis (97% vs 95%; p=0.28), macular thickness (264.89±59.74 vs 250.62±36.85; p=0.15), best-corrected visual acuity (0.67±0.34 vs 0.81±0.26; p=0.001), and drug retention (84.95% vs 95.24%; p=0.042). CONCLUSION: Although IFX and ADA yields efficacy refractory BD uveitis, ADA appears to be associated with better outcome than IFX after one-year follow-up. This article is protected by copyright. All rights reserved.

2.
Expert Opin Biol Ther ; 19(4): 273-286, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30827128

RESUMO

INTRODUCTION: Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predominance of systemic symptoms and another manifested by progressive chronic polyarthritis. Glucocorticoids remain the mainstay in the treatment of AOSD. However, biologic therapies are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main retrospective and prospective studies, and case series on the use of the anti-interleukin (IL)-6 receptor tocilizumab in AOSD. Expert opinion: Since IL-6 serum levels are highly increased in both active systemic and polyarticular phenotypes, IL-6 blockade was considered to be a plausible therapeutic option for the management of AOSD. Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSD, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications. Nevertheless, there are some reports describing patients who are refractory to any therapy. Future research should focus on the identification of prognostic biomarkers that help us to tailor an individualized treatment for each type of patient and in the search of new disease activity indices that help us to monitor the response to the therapy more closely.

3.
Am J Ophthalmol ; 200: 85-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30660771

RESUMO

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.

4.
Expert Rev Clin Immunol ; 14(12): 979-992, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30324816

RESUMO

INTRODUCTION: Adult onset Still's disease (AOSD) is an uncommon systemic inflammatory disease on the clinical spectrum of autoinflammatory disorders. Its presentation and clinical course may result in several well-differentiated phenotypes: from a systemic and highly symptomatic pattern to a chronic articular pattern. Overproduction of numerous pro-inflammatory cytokines is observed in AOSD. Anakinra (ANK), a human interleukin (IL)-1R antagonist, has recently been approved in the EU for the treatment of AOSD. Areas covered: In this review, we discuss the main studies on the efficacy and safety on ANK for the treatment of AOSD. The vast majority of them are retrospective studies and case series. Expert commentary: Overall, ANK is an effective biologic agent for the treatment of AOSD, especially for the systemic pattern and also for those patients who have life-threatening complications, which frequently occur over the course of the disease. The initial dose usually indicated of ANK in adults is 100 mg/day subcutaneously, although dose reduction can be performed in some cases once the disease is under control. The safety profile of ANK is favorable and similar to that described in other rheumatic diseases. In conclusion, ANK is an effective and safe agent for the treatment of AOSD.

5.
Ophthalmology ; 125(9): 1444-1451, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29602570

RESUMO

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.

6.
Rheumatology (Oxford) ; 57(5): 856-864, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29471416

RESUMO

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 Jovem
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