Peripheral ulcerative keratitis in rheumatoid arthritis patients taking tocilizumab: paradoxical manifestation or insufficient efficacy?

Abstract

Objectives Peripheral ulcerative keratitis (PUK) is a severe corneal condition associated with uncontrolled rheumatoid arthritis (RA). Tocilizumab (TCZ) is used to control RA, however, episodes of paradoxical ocular inflammation have been reported in TCZ-treated patients. We report a case series of PUK in TCZ-treated RA patients with ophthalmological and systemic findings and discuss the potential underlying mechanisms. Methods Four patients (6 eyes), aged 47–62 years were included. At the onset of PUK, the median duration of RA was 13 years (3–13), and the median treatment with TCZ was 9 months (3–14). Two patients had active disease (DAS 28 > 3.2) and the disease was controlled in 2 patients (DAS 28 ≤ 3.2). Results TCZ was initially replaced by another immunomodulatory treatment in all patients and later reintroduced in 2 patients without PUK recurrence. Corneal inflammation was controlled in all cases with local and systemic treatments, with severe visual loss in one eye. Conclusion To summarize, PUK may occur in patients with long standing RA after a switch to TCZ and can be interpreted, depending on the context, as insufficient efficacy or a paradoxical manifestation. These cases highlight the urgent need for reliable biomarkers of the efficacy/paradoxical reactions for biologics.

Tocilizumab in rheumatoid arthritis‐associated peripheral ulcerative keratitis: A 1‐year follow‐up case report

“…23 Cohen reported that rare cases of PUK may occur in patients with long-standing RA after a switch to tocilizumab. 24 However, our patient had PUK before the use of tocilizumab, and her condition was gradually relieved by treatment with tocilizumab and local therapies. It is suggested that PUK can be effectively relieved by tocilizumab in some patients; however, the effect needs to be closely monitored, and the treatment plan needs to be adjusted quickly in the case of inefficacy.…”

“…In patients with RA and small paracentral corneal ulcerations or perforations, the application of tissue adhesive and a bandage contact lens and the introduction of topical cyclosporine may be the preferred initial treatment 23 . Cohen reported that rare cases of PUK may occur in patients with long‐standing RA after a switch to tocilizumab 24 . However, our patient had PUK before the use of tocilizumab, and her condition was gradually relieved by treatment with tocilizumab and local therapies.…”

Baricitinib in severe and refractory peripheral ulcerative keratitis: a case report and literature review

“…38 TCZ has also shown efficacy in other refractory inflammatory diseases, including ocular diseases. [39][40][41][42][43][44][45] TCZ may be useful in PUK associated to RA. 26 Paradoxically, PUK has been described in RA patients receiving TCZ, which can be interpreted as a lack of efficacy or as a paradoxical reaction to the drug.…”