Efficacy and Safety of Infliximab in HLA-B27-associated Ocular Inflammation Refractory or Intolerant to Conventional Immunomodulatory Therapy.

Asima Bajwa,Adriana Fandiño,Charles Stephen Foster,Abhishek R Payal,Arash Maleki,María Inés Menéndez Padrón,Marisa Walsh

doi:10.18502/jovr.v15i4.7786

Abstract

PurposeTo determine the efficacy and safety of infliximab therapy in patients with HLA B-27-associated ocular inflammation resistant or intolerant to conventional immunomodulatory therapy.MethodsThis was a retrospective observational case series. All cases were uveitic patients with positive HLA-B27, confirmed through HLA testing, resistant or intolerant to conventional immunomodulatory therapy. The primary outcome of the study was to identify the efficacy of infliximab determined by the control of inflammation, duration of remission, and the ability to reduce conventional immunomodulatory therapy. The secondary outcome was an improvement of two or more lines of best-corrected visual acuity (BCVA) on the Snellen visual acuity chart.ResultsTwenty-four patients (38 eyes) were included in the study. All patients were followed for 24 months. Twenty-one (87.5%) patients completed 24 months of follow-up. Sixteen (66.7%) patients had active uveitis at the beginning of therapy. One patient out of these active patients had active inflammation at the end of follow-up period. Thirteen (87.5%) out of sixteen active patients were in steroid-free remission. The mean duration of treatment to induce remission was 16.5 months (range 6–24 months). Corticosteroid was stopped in 19 (90.5%) patients by the end of the study. At the end of the study, in patients who achieved remission, 14 (58.3%) patients were in remission on infliximab therapy and 6 (25%) patients were in remission off infliximab therapy. Of the 38 eyes, 8 (21.05%) showed improvement in BCVA (three eyes had successful cataract extraction with intraocular lens implantation during infliximab therapy with no subsequent inflammation), while 26 eyes (68.4%) had stable BCVA over the 24-month study period. The side effects included allergic reaction, fatigue, cellulitis, headache, restlessness, elevation of liver enzymes, and anemia. Two patients (n = 24, 8.3%) experienced severe adverse effects and the treatment was stopped prematurely in these two patients.ConclusionInfliximab might induce and maintain the steroid-free remission in HLA-B27-associated ocular inflammation in patients resistant or intolerant to conventional immunomodulatory therapy.

Highlights

Acute anterior uveitis (AAU) is the most common form of intraocular inflammatory disease and can be associated with the human leukocyte antigen (HLA)-B27 haplotype in approximately 55–71% of patients.[1, 2] It usually manifests at a young age as recurrent, acute, non-granulomatous uveitis, with a unilateral or alternating bilateral presentation
Sixteen patients (n = 24, 66.7%) at baseline had active ocular inflammation, which was reduced to only one patient (n = 21, 4.7%) at the 24-month followup visit (Table 2)
TNF-α gene controls the production of TNF-α, which is a cytokine and inflammatory mediator in animal models of uveitis

Summary

Introduction

Acute anterior uveitis (AAU) is the most common form of intraocular inflammatory disease and can be associated with the human leukocyte antigen (HLA)-B27 haplotype in approximately 55–71% of patients.[1, 2] It usually manifests at a young age as recurrent, acute, non-granulomatous uveitis, with a unilateral or alternating bilateral presentation. The disease may involve posterior segment in the form of optic disc edema, macular edema, choroidal folds and effusions, exudative retinal detachment, and anterior and posterior scleritis.[3] Intense inflammation and protein coagulum in the aqueous may lead to temporary or permanent severe visual impairment. The first line of therapy, are sometimes insufficient to control the intraocular inflammation. Additional periocular and/or systemic corticosteroids and sometimes both are required to control the inflammation in more severe cases. Corticosteroidsparing conventional immunomodulatory therapies such as methotrexate, azathioprine, and mycophenolate mofetil (MMF) have been employed in the treatment of these patients. Biologic response modifier agents are the step of the step ladder approach in the treatment of patients intolerant or resistant to conventional immunomodulatory therapy (IMT).[4, 5]

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