Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease

Martín-Varillas, J. L.; Calvo-Río, V.; Beltrán, E.; Sánchez‐Bursón, Juan; Mesquida, Marina; Adán, Alfredo; Hernández, José L.; Garfella, M. Hernández; Pascual, Elia Valls; Martínez-Costa, Lucía; Sellas‐Fernández, Agustí; Cordero‐Coma, Miguel; Díaz-Llopis, M.; Gallego, Roberto; Salom, David; Ortego, N.; García-Serrano, J.L.; Callejas‐Rubio, José Luis; Herreras, José M.; García‐Aparicio, Ángel; Maíz, O.; Blanco, Ana; Torre, I.; Díaz-Valle, D.; Pato, Esperanza; Aurrecoechea, Elena; Caracuel, Miguel A.; Gamero, Fernando; Minguez, E; Carrasco‐Cubero, Carmen; Olivé, Alejandro; Vázquez, J; Ruiz-Moreno, Ó.; Manero, Javier; Muñóz-Fernández, Santiago; Martínez, Myriam Gandia; Rubio‐Romero, Esteban; Miera, F. Javier Toyos-Sáenz de; Longo, Francisco; Nolla, Joan M.; Revenga, Marcelino; González-Vela, Carmen; Loricera, J.; Atienza‐Mateo, Belén; Demetrio‐Pablo, Rosalía; Hernández, José L.; González-Gay, Miguel Á.; Blanco, R.

doi:10.1016/j.ophtha.2018.02.020

Cited by 54 publications

(24 citation statements)

References 36 publications

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“…However, it was necessary to address the safety of anti-TNF-a treatment here. In this review, we found that 22 patients (2.62% of all included patients) experienced severe AEs (Al Rashidi et al, 2013;Bejerano et al, 2013;Hamuryudan et al, 2013;Mesquida et al, 2013;Calvo-Rıó et al, 2014;Domıńguez Casas et al, 2017;Fabiani et al, 2017;Martıń-Varillas et al, 2018), while some minor AEs such as infusion reactions (rash, itchiness, or respiratory distress) and gastroenteritis happened frequently. Infectious AEs, such as tuberculosis, pneumonia, bacteremia, urinary tract, and upper airway infections, were the main severe AEs.…”

Section: Discussionmentioning

confidence: 99%

“…2013; Mesquida et al, 2013;Calvo-Rıó et al, 2014;Takeuchi et al, 2014;Domıńguez Casas et al, 2017;Fabiani et al, 2017;El Garf et al, 2018;Martıń-Varillas et al, 2018;Katsuyama et al, 2019;Yalcindag and Kose, 2019) included safety information with more than 109 patients ( Table 3). According to the available data, 22 patients (2.62%) experienced severe AEs.…”

Section: Adverse Eventsmentioning

confidence: 99%

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Effectiveness and Safety of Anti-Tumor Necrosis Factor-Alpha Agents Treatment in Behcets’ Disease-Associated Uveitis: A Systematic Review and Meta-Analysis

Huang

Yang

et al. 2020

Front. Pharmacol.

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Purpose: We conducted a systematic review and meta-analysis to determine the effectiveness and safety of anti-tumor necrosis factor-alpha (TNF-a) agents in the treatment of Behcets' disease (BD)-associated uveitis. Method: Three electronic databases, Embase, MEDLINE, and the Cochrane Library, were searched for eligible papers focusing on the anti-TNF-a agents treatment in BD-associated uveitis with at least 6 months follow-up time. A systematic review and meta-analysis was conducted on selected papers with appropriate clinical and methodological homogeneity. The effectiveness outcomes included inflammation remission, visual acuity (VA) improvement, central macular thickness (CMT) decrease, corticosteroid (CS)-sparing effects, and the safety outcomes included minor and severe drug-related adverse events (AEs). Result: From Jan 2010 to Dec 2019, there were 504 records produced in total, in which 18 clinical trials were selected for meta-analysis (15 trials were retrospective studies, and 3 were prospective studies). The number of patients in each study ranged from 11 to 163 and the mean follow-up time from 0.9 to 6.44 years. During the follow-up, the pooled inflammation remission rate was 68% with a 95% confidence interval (CI) of 0.59-0.79, VA improvement rate was 60% (95% CI 0.47-0.77), CMT decrease was 112.70 mm (95% CI 72.8-153.0 mm). The proportions of patients who had CS-suspended and CS-tapered reached 38% (95% CI 0.23-0.65) and 34% (95% CI 0.16-0.70), respectively. The severe AEs were reported but not common, which included severe infusion reactions, pneumonia, bacteremia, tuberculosis, melanoma, and lymphoma. Conclusion: Anti-TNF-a agents treatment has high effectiveness including efficient inflammation remission, satisfactory VA improvement, obvious CMT reduction, and significant CS-sparing effects. Although some drug-related AEs were reported, the incidence of severe AEs was acceptable. Anti-TNF-a agents treatment is a promising option for controlling BD-associated uveitis.

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Section: Discussionmentioning

confidence: 99%

Section: Adverse Eventsmentioning

confidence: 99%

Effectiveness and Safety of Anti-Tumor Necrosis Factor-Alpha Agents Treatment in Behcets’ Disease-Associated Uveitis: A Systematic Review and Meta-Analysis

Huang

Yang

et al. 2020

Front. Pharmacol.

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“…The quality assessment of the included clinical trials and observational studies is reported in Supplementary Table S1 and Table S2. Melikoglu et al [55] was judged as low risk of bias, Markomichelakis et al [56], Zou et al [57], and Martin-Varillas et al [58] were judged at high risk of bias. The randomization process in the latter three caused this high risk of bias.…”

Section: Systematic Review Into Anti-tnf-α Treatmentmentioning

confidence: 99%

“…Both Zou [57] et al and Martin-Varillas [58] et al compare different dosages of anti-TNF-α treatment. Both groups provide evidence for a comparable efficacy in treatment with a lower or reduced dose.…”

Section: Efficacy Of Treatmentmentioning

confidence: 99%

Behҫet’s Disease, and the Role of TNF-α and TNF-α Blockers

Houwen

Laar

2020

IJMS

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In this both narrative and systematic review, we explore the role of TNF-α in the immunopathogenesis of Behçet’s disease (BD) and the effect of treatment with TNF-α blockers. BD is an auto-inflammatory disease, characterized by recurrent painful oral ulcerations. The pathogenesis of BD is not yet elucidated; it is assumed that TNF-α may play a key role. In the narrative review, we report an increased production of TNF-α, which may be stimulated via TLR-signaling, or triggered by increased levels of IL-1β and IFN-γ. The abundance of TNF-α is found in both serum and in sites of inflammation. This increased presence of TNF-α stimulates T-cell development toward pro-inflammatory subsets, such as Th17 and Th22 cells. Treatment directed against the surplus of TNF-α is investigated in the systematic review, performed according to the PRISMA guideline. We searched the Pubmed and Cochrane database, including comparative studies only. After including 11 studies, we report a beneficial effect of treatment with TNF-α blockers on the various manifestations of BD. In conclusion, the pivotal role of TNF-α in the immunopathogenesis of BD is reflected in both the evidence of their pro-inflammatory effects in BD and in the evidence of the positive effect of treatment on the course of disease in BD.

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“…In positive cases, prophylaxis with isoniazid was initiated for at least 4 weeks before using the biologic treatment and was maintained for 9 months. The presence of malignancies was excluded in all patients [31][32][33][34][35][36][37][38][39].…”

Section: Design and Enrollment Criteriamentioning

confidence: 99%

Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune-Mediated Inflammatory Diseases. A Multicenter Study

Herrero-Morant

Álvarez-Reguera

Martín-Varillas

et al. 2020

JCM

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We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 ± 13.9 years). The underlying diseases were Bechet’s disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean ± SD BCVA (0.8 ± 0.3 LogMAR vs. 0.6 ± 0.3 LogMAR; p = 0.03), mean ± SD RNFL (190.5 ± 175.4 μm vs. 183.4 ± 139.5 μm; p = 0.02), mean ± SD MT (270.7 ± 23.2 μm vs. 369.6 ± 137.4 μm; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10–61.5) mg/day at baseline to. 2.5 (0–5) mg/day after one year of follow-up; p = 0.001. After a mean ± SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is effective in patients with refractory non-MS ON.

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Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease

Abstract: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

Cited by 54 publications

References 36 publications

Effectiveness and Safety of Anti-Tumor Necrosis Factor-Alpha Agents Treatment in Behcets’ Disease-Associated Uveitis: A Systematic Review and Meta-Analysis

Effectiveness and Safety of Anti-Tumor Necrosis Factor-Alpha Agents Treatment in Behcets’ Disease-Associated Uveitis: A Systematic Review and Meta-Analysis

Behҫet’s Disease, and the Role of TNF-α and TNF-α Blockers

Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune-Mediated Inflammatory Diseases. A Multicenter Study

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