Non-anti-TNF biologic modifier drugs in non-infectious refractory chronic uveitis: The current evidence from a systematic review

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Abstract

Objective

To examine, separately, in children and adults with autoimmune chronic uveitis (ACU), the evidence regarding the effectiveness and the safety of switching to a non-anti-TNF biologic modifier immunosuppressant treatment (NTT) currently available in clinical practice.

Methods

A systematic search between January 2000 and April 2014 was conducted using EMBASE, Ovid MEDLINE, Evidence Based Medicine Reviews—ACP Journal Club, Cochrane libraries, and EBM Reviews. Studies investigating the efficacy of NTT as a biologic modifier immunosuppressant medication for ACU, refractory to topical and/or systemic steroid therapy, were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, as defined by the SUN working group criteria. We determined a combined estimate of the proportion of subjects responding to NTT.

Results

We initially identified 526 articles, of which 89 were potentially eligible. From the selection process, a total of 10 retrospective chart reviews and a randomized single-blind controlled study, providing a total of 12 children and 34 adults, were deemed eligible: 3 articles looked at rituximab, 3 at abatacept, 3 at tocilizumab, and the remaining 1 at alemtuzumab and the other at anakinra. Before the NTT treatment, all the eligible subjects received several combinations of one or more DMARDs and at least one anti-TNF strategy. With the exclusion of 7 adults enrolled in the RCT, 8 of 12 children and 18 of 27 adults responded to NTT treatment: 0.66 was the combined estimate of the proportion of subjects improving on NTT treatment in children (95% CI: 0.46−0.99) and in adults (95% CI: 0.49–0.84). Further statistical comparison between different NTT strategies was not possible due to the small sample size.

Conclusion

Although randomized controlled trials are needed, the available evidence suggests the clinical use of a NTT strategy in selected categories of ACU, refractory to previous course of immunosuppressive treatment, DMARDs, as well as anti-TNFα, in adults as well as children.

Introduction

Non-infectious chronic uveitis is a serious and disabling sight-threatening disease accounting for up to 10% of pathologies leading to blindness [1]. Currently, a step-by step escalating immunosuppressive therapy is generally used, in children as well as in adults, and anti-TNFα biologic therapies have markedly increased the treatment options for sight-threatening uveitis refractory to conventional immune-modulatory therapy (DMARD) in addition to topical and/or systemic corticosteroids [2], [3]. However, a subset of patients fails to respond to TNFα blockers or is unable to tolerate these therapies and may therefore benefit from switching to another drug [4], [5]. Overall, about 25% of children with autoimmune chronic uveitis (ACU) who received adalimumab and infliximab do not respond to these treatments [6]. In this clinical setting, the availability of several different molecules, mostly off-label, poses the clinical question whether it can be useful and safe to administer another class of biologic drugs, such as abatacept or rituximab, for patients with refractory autoimmune uveitis. To the best of our knowledge, to date, there has been no systematic evaluation on this topic. However, efficacy, availability of systemic treatments, as well as their potential side effects can be different between adults and children. The aim of our study was therefore to examine, separately, in children and adults with autoimmune chronic uveitis (ACU), the evidence regarding the effectiveness and the safety of switching to a non-anti-TNF biologic response modifier immunosuppressant treatment (NTT) currently available in clinical practice.

Section snippets

Methods

A systematic review was conducted and is reported according to the PRISMA guidelines.

Results

A total of 526 articles were identified by searches of databases, and, from these, 442 were excluded by examination of their titles and abstracts (Fig. 1). Excluded studies were mainly duplicates, studies on diseases other than autoimmune non-infectious uveitis (i.e., scleritis or inflammatory orbital diseases), studies on overall mortality among patients receiving immunosuppressive treatment, and studies on biologic modifier treatment other than NTT. Full text of the remaining 84 studies and 5

Discussion

We have estimated that the overall probability of improvement of uveitis, in both children and in adults, with ACU, refractory to previous DMARD and/or anti-TNFα treatments, treated with a NTT strategy, is 0.66. This evidence suggests that NTT agents can be efficacious treatment in this specific clinical setting. No eligible children received tocilizumab or alemtuzumab, and no adult received an anti-IL-1-blocking strategy. In both the age groups, there were not enough data to attempt a powered

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