Expert opinion on the use of biological therapy in non-infectious uveitis

Touhami, Sara; Diwo, É.; Sève, P.; Trad, S.; Bielefeld, P.; Sène, Damien; Abad, S.; Brézin, Antoine P.; Quartier, Pierre; Paut, Isabelle Koné; Weber, Michel; Chiquet, Christophe; Errera, Marie‐Hélène; Sellam, Jérémie; Cacoub, P.; Kaplanski, Gilles; Kodjikian, Laurent; Bodaghi, Bahram; Saadoun, David

doi:10.1080/14712598.2019.1595578

Cited by 60 publications

(47 citation statements)

References 106 publications

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“…6). 114 CSs are proposed in the case of severe nonanterior uveitis (optic neuropathy, macular edema with visual acuity <20/200, or occlusive retinal vasculitis with retinal ischemia), especially when both eyes are involved. In addition, systemic therapy is used in patients who are resistant, and/or intolerant to local treatment, and/or have active systemic disease requiring treatment.…”

Section: Corticosteroidsmentioning

confidence: 99%

Ocular Sarcoidosis

Sève

Jamilloux

Tilikete

et al. 2020

Semin Respir Crit Care Med

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Sarcoidosis is one of the leading causes of inflammatory eye disease. Any part of the eye and its adnexal tissues can be involved. Uveitis and optic neuropathy are the main manifestations, which may require systemic treatment. Two groups of patients with sarcoid uveitis can be distinguished: one of either sex and any ethnicity in which ophthalmological findings are various and another group of elderly Caucasian women with mostly chronic posterior uveitis. Clinically isolated uveitis revealing sarcoidosis remains a strictly ocular condition in a large majority of cases. Although it can be a serious condition involving functional prognosis, early recognition in addition to a growing therapeutic arsenal (including intravitreal implant) has improved the visual prognosis of the disease in recent years. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema. In up to 30% of the cases that require an unacceptable dosage of corticosteroids to maintain remission, additional immunosuppression is used, especially methotrexate. As with other forms of severe noninfectious uveitis, monoclonal antibodies against tumor necrosis factor-α have been used. However, only very rarely does sarcoid uveitis fail to respond to combined corticosteroids and methotrexate therapy, a situation that should suggest either poor adherence or another granulomatous disease. Optic neuropathy often affects women of African and Caribbean origins. Some authors recommend that patients should be treated with high-dose of corticosteroids and concurrent immunosuppression from the onset of this manifestation, which is associated with a poorer outcome.

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Section: Corticosteroidsmentioning

confidence: 99%

Ocular Sarcoidosis

Sève

Jamilloux

Tilikete

et al. 2020

Semin Respir Crit Care Med

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“…Alternatively, intravitreal injections of steroids can be suggested to treat unilateral macular edema or when it resists systemic therapy and periocular injections. 63 Inhaled CS are not effective on lung disease but may help in reducing or stopping cough when there is no indication for a general treatment. 43 Second-Line Treatment (i.e.,…”

Section: What Are Sarcoidosis First-line Treatments?mentioning

confidence: 99%

<p>Refractory Sarcoidosis: A Review</p>

Jammal

Jamilloux

Gerfaud‐Valentin

et al. 2020

TCRM

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Sarcoidosis is a multi-system disease of unknown etiology characterized by granuloma formation in various organs (especially lung and mediastinohilar lymph nodes). In more than half of patients, the disease resolves spontaneously. When indicated, it usually responds to corticosteroids, the first-line treatment, but some patients may not respond or tolerate them. An absence of treatment response is rare and urges for verifying the absence of a diagnosis error, the good adherence of the treatment, the presence of active lesions susceptible to respond since fibrotic lesions are irreversible. That is when second-line treatments, immunosuppressants (methotrexate, leflunomide, azathioprine, mycophenolate mofetil, hydroxychloroquine), should be considered. Methotrexate is the only first-line immunosuppressant validated by a randomized controlled trial. Refractory sarcoidosis is not yet a well-defined condition, but it remains a real challenge for the physicians. Herein, we considered refractory sarcoidosis as a disease in which second-line treatments are not sufficient to achieve satisfying disease control or satisfying corticosteroids tapering. Tumor necrosis alpha inhibitors, third-line treatments, have been validated through randomized controlled trials. There are currently no guidelines or recommendations regarding refractory sarcoidosis. Moreover, criteria defining non-response to treatment need to be clearly specified. The delay to achieve response to organ involvement and drugs also should be defined. In the past ten years, the efficacy of several immunosuppressants beforehand used in other autoimmune or inflammatory diseases was reported in refractory cases series. Among them, anti-CD20 antibodies (rituximab), repository corticotrophin injection, and anti-JAK therapy anti-interleukin-6 receptor monoclonal antibody (tocilizumab) were the main reported. Unfortunately, no clinical trial is available to validate their use in the case of sarcoidosis. Currently, other immunosuppressants such as JAK inhibitors are on trial to assess their efficacy in sarcoidosis. In this review, we propose to summarize the state of the art regarding the use of immunosuppressants and their management in the case of refractory or multidrugresistant sarcoidosis.

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“…Non-infectious uveitis is currently being treated by using corticosteroids, general immunosuppressants, or specific antibodies [18,19]. While these treatments provide temporary relief, they are associated with side effects that include cataract formation, increased susceptibility to infection, and elevated intraocular pressure [20].…”

Section: Introductionmentioning

confidence: 99%

A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis

et al. 2020

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Experimental autoimmune uveitis (EAU) in rodents recapitulates many features of the disease in humans and has served as a useful tool for the development of therapeutics. A peptide from C-terminus of interferon α1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFNα-C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFNα-C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNFα were suppressed when IFNα-C was simultaneously present. TNF-α mediated induction of NF-κB and signaling by IL-17A were attenuated by IFNα-C. Differentiated ARPE-19 cells were treated with TNFα in the presence or absence IFNα-C and analyzed by immmunhistochemistry. IFNα-C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNFα was prevented by IFNα-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFNα-C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFNα-C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigen-specific T cell proliferation that was inhibited in the presence of IFNα-C. IFNα-C peptide exhibits anti-inflammatory properties and protects mice against damage to retinal structure and function suggesting that it has therapeutic potential for the treatment of autoimmune uveitis. Citation: Ahmed CM, Ildefonso CJ, Johnson HM, Lewin AS (2020) A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis. PLoS ONE 15(2): e0227524.

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Expert opinion on the use of biological therapy in non-infectious uveitis

Cited by 60 publications

References 106 publications

Ocular Sarcoidosis

Ocular Sarcoidosis

<p>Refractory Sarcoidosis: A Review</p>

A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis

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