Elsevier

Ophthalmology

Volume 129, Issue 5, May 2022, Pages 520-529
Ophthalmology

Original Article
Anti–Tumor Necrosis Factor α versus Tocilizumab in the Treatment of Refractory Uveitic Macular Edema: A Multicenter Study from the French Uveitis Network

https://doi.org/10.1016/j.ophtha.2021.11.013Get rights and content

Purpose

To analyze the factors associated with response (control of ocular inflammation and corticosteroid-sparing effect) to biologics (anti–tumor necrosis factor [TNF]-α agents and tocilizumab) in patients with refractory uveitic macular edema (ME).

Design

Multicenter, retrospective, observational study.

Participants

Adult patients with uveitic ME refractory to systemic corticosteroids, disease-modifying antirheumatic drugs, or both.

Methods

Patients received anti–TNF-α agents (infliximab 5 mg/kg at week 0, 2, 6, and every 4–6 weeks [n = 69] and adalimumab 40 mg/2 weeks [n = 80]) and tocilizumab (8 mg/kg every 4 weeks intravenously [n = 39] and 162 mg/week subcutaneously [n = 16]).

Main Outcome Measures

Analysis of complete and partial response rates, relapse rate, low vision (visual acuity in at least 1 eye of ≥ 1 logarithm of the minimum angle of resolution), corticosteroid-sparing effect, and adverse events at 6 months.

Results

Two hundred four patients (median age, 40 years [interquartile range, 28–58 years]; 42.2% men) were included. Main causes of uveitis included Behçet’s disease (17.2%), birdshot chorioretinopathy (11.3%), and sarcoidosis (7.4%). The overall response rate at 6 months was 46.2% (21.8% of complete response) with anti–TNF-α agents and 58.5% (35.8% of complete response) with tocilizumab. In multivariate analysis, treatment with tocilizumab (odds ratio, 2.10; 95% confidence interval [CI], 1.06–4.06; P = 0.03) was associated independently with complete response of uveitic ME compared with anti–TNF-α agents. Anti–TNF-α agents and tocilizumab did not differ significantly in terms of relapse rate (hazard ratio, 1.00; 95% CI, 0.31–3.18; P = 0.99) or occurrence of low vision (odds ratio, 1.02; 95% CI, 0.51–2.07; P = 0.95) or corticosteroid-sparing effect (P = 0.29). Adverse events were reported in 20.6% of patients, including serious adverse events reported in 10.8% of patients.

Conclusions

Tocilizumab seems to improve complete response of uveitic ME compared with anti–TNF-α agents.

Section snippets

Patients

This was a multicenter, retrospective, observational study conducted in participating internal medicine and ophthalmology departments of the French Uveitis Network between 2018 and 2020. Adult patients with refractory uveitic ME were included. Refractory ME was defined as ME resistant to a first-line therapy with systemic corticosteroids or disease-modifying antirheumatic drugs (i.e., mycophenolate mofetil, methotrexate, azathioprine, etc.) and that requires treatment escalation with anti–TNF-α

Results

Baseline data are summarized in Table 1. Two hundred four patients (57.8% women; median age, 40 years [IQR, 28–58 years]) were included in the study: 149 patients (73%) were treated with anti–TNF-α agents (80 with adalimumab and 69 with infliximab) and 55 patients (27%) received tocilizumab (39 intravenous and 16 subcutaneous). One hundred ten patients (53.9%) had panuveitis and 77 patients (37%) had retinal vasculitis. The main causes of uveitis were Behçet’s disease (35 patients [17.2%]),

Discussion

In this multicenter study, the French Uveitis Network analyzed the efficacy of anti–TNF-α agents or tocilizumab to control ocular inflammation and corticosteroid-sparing effect in a cohort of patients with refractory ME in sight-threatening noninfectious uveitis. The main conclusions drawn from this study are: (1) tocilizumab improved the odds of complete response of uveitic ME by 2 times as compared with anti–TNF-α agents, (2) risk of low VA in uveitic ME was increased by 3 times in Behçet’s

Acknowledgments

The authors thank Nikki Sabourin-Gibbs, Rouen University Hospital, for her help in editing the manuscript.

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      Citation Excerpt :

      Although TCZ is not approved for the treatment of uveitis, some studies suggest the efficacy of TCZ in highly refractory CME cases [18,22,32]. Nonetheless, we only found a recent study comparing anti-TNF agents with TCZ in CME related BD [34]. Taking all these considerations into account, this multicenter study aims to compare the efficacy of anti-TNF, specifically ADA and IFX, with TCZ in patients with refractory CME due to BD.

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    Supplemental material available at www.aaojournal.org.

    Disclosure(s):

    All authors have completed and submitted the ICMJE disclosures form.

    The author(s) have made the following disclosure(s): P.S.: Lecturer – AbbVie, Chugai

    P.B.: Financial support – AbbVie, UCB, Novartis, MSD

    S.T.: Consultant and Financial support – Allergan, Novartis Horus, Bayer Pharma

    P.C.: Consultant, Advisory board, Financial support, Lecturer – Alnylam, Bayer, Innotech, Janssen, Mylan, Pfizer, Servier, Vifor, CNRS, INSERM, Université Pierre et Marie Curie

    B.B.: Consultant – AbbVie, Allergan, Alimera, Novartis, Optos, Santen, Thea

    D.S.: Consultant – AbbVie, Roche Chugai

    HUMAN SUBJECTS: Human subjects were included in this study. The human ethics committees at Pitie-Salpêtrière Hospital approved the study. All research adhered to the tenets of the Declaration of Helsinki. Informed consent was not required as per French regulations for research on humans because of the retrospective strictly observational nature of the study.

    No animal subjects were included in this study.

    Author Contributions:

    Conception and design: Sève, Bielefeld, Sené, Cacoub, Bodaghi, Biard, Saadoun

    Analysis and interpretation: Leclercq, Andrillon, Maalouf, El Chamieh, Biard, Saadoun

    Data collection: Leclercq, Maalouf, Sève, Bielefeld, Gueudry, Sené, Moulinet, Rouvière, Sène, Desbois, Domont, Touhami

    Obtained funding: N/A; Study was performed as part of regular employment duties at French Uveitis Network. No additional funding was provided.

    Overall responsibility: Leclercq, Andrillon, Maalouf, Gueudry, Touhami, Cacoub, Bodaghi, Biard, Saadoun

    These authors contributed equally as first authors.

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