Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients
Introduction
The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory diseases characterized by joint involvement and extra-articular manifestations strongly associated with HLA B27 antigen [1], [2], [3], [4]. It includes reactive arthritis (formerly called Reiter syndrome), ankylosing spondylitis (AS), inflammatory bowel disease (Crohn′s disease and ulcerative colitis), undifferentiated SpA and psoriatic arthritis (PsA) [1], [2], [3], [4].
Uveitis, the most common extra-articular manifestation of SpA [5], [6], has been included in the recently proposed classification criteria for axial and peripheral SpA [7], [8]. The most frequent pattern of ocular involvement in SpA is a recurrent acute unilateral anterior uveitis, which usually resolves with topical therapy [9], [10]. In some cases, however, uveitis may be refractory or relapsing, and treatment with an additional conventional immunosuppressive agents (mainly sulfasalazine or methotrexate) may be required [9], [11], [12], [13].
Despite using topical and conventional immunosuppressive agents, uveitis sometimes becomes chronic or relapsing leading to major ocular sequelae. According to published data, up to one-third of patients experience substantial visual impairment and up to 10% become blind [9], [10], [14], [15]. Based on the recent Expert Panel Recommendations, infliximab (IFX), or adalimumab (ADA) are used when SpA-related severe, visual threatening or debilitating uveitis occurs [9]. These recommendations are based on several studies showing the efficacy of anti-tumor necrosis factor-alpha (anti-TNF-α) agents in uveitis associated with SpA [16], [17], [18], [19]. With respect to this, monoclonal antibodies seem to be more effective than the soluble receptor etanercept in most cases of uveitis [20] including SpA-related uveitis [21].
Although IFX or ADA are the first-line recommended monoclonal antibodies for the management of SpA-uveitis refractory to conventional drugs, in some cases inadequate response, due to either intolerance or inefficacy, may be observed following the use of these two biologic agents. These patients represent a major challenge for the clinician, since no well-establish approach has been suggested to deal with these cases. To provide an alternative therapeutic option in refractory SpA-related uveitis, we have used Golimumab (GLM), a novel fully humanized anti-TNF-α monoclonal antibody that has been approved for the treatment of rheumatoid arthritis, PsA, AS, and ulcerative colitis [22], [23], [24]. Compared to IFX, GLM is administered by subcutaneous route and has a lower risk for developing neutralizing antibodies. Moreover, it has potential advantages over ADA, as its monthly administration. However, the few published studies on the efficacy of GLM in refractory uveitis are based on small case series [25] or heterogeneous subgroups of patients with this disorder [26], [27], [28], [29], [30], [31], [32].
Taking into account all these considerations, we conducted a multicenter study to analyze the clinical response to GLM in patients diagnosed with SpA-related uveitis refractory to other systemic immunosuppressive agents.
Section snippets
Patients and methods
This is an open-label, multicenter study including 15 patients with SpA-related uveitis. All of them had been refractory to previous standard synthetic immunosuppressive drugs and in some cases to at least 1 anti-TNF-α agent.
Baseline features
Overall, 15 patients (18 affected eyes) with SpA-related uveitis who were treated with GLM were assessed. The main baseline characteristics of this series of patients are summarized in Table 1. As expected, most patients were young men [n = 13; 86.7%; mean age = 39 ± 6 years; median (range) age: 39 (31–48) years], and HLA-B27 was positive in 11 cases. The most frequent underlying SpA subtype was AS (n = 8) followed by PsA (n = 6) and non-radiographic axial SpA (n = 1).
The most common synthetic
Discussion
Herein, we report on 15 patients with SpA-related uveitis refractory to synthetic conventional immunosuppressive drugs, 10 of them also refractory to anti-TNF-α agents. Most of them achieved response to GLM therapy.
Uveitis prevalence in SpA ranges from 10% to 50% depending on the selected study [6], [41], the subtype of SpA (it is higher in AS and lower in undifferentiated SpA) [6], and HLA-B27 positivity (ranging between 40% and 48% in HLA-B27 positive and 15–25% in HLA-B27 negative patients)
Conclusion
In conclusion, our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis.
Acknowledgments
This work was partially supported by RETICS Program, RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain).
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2020, Seminars in Arthritis and RheumatismCitation Excerpt :Certolizumab, in a double-blind placebo-controlled trial, showed a lower rate of uveitis in patients with axial spondyloarthritis compared to placebo [46], and there are several case reports supporting its effectiveness in active NINA uveitis [47]. Golimumab efficacy has been described in several case series, achieving control of ocular inflammation, maintaining remission and showing corticosteroid sparing effects [48–53]. On the other hand, etanercept is not recommended for the treatment of uveitis based on a lack of efficacy reported in different studies [54].
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- 1
V. Calvo-Río and R. Blanco contributed equally to this work and shared first authorship.
- 2
J.L. Hernández and Miguel A. González-Gay1 shared senior authorship.