We thank Drs Singh and Sangwan for their interest in our article, “Use of Infliximab in the Treatment of Peripheral Ulcerative Keratitis in Crohn Disease,” and are heartened that they have found a similar effect of this class of biologic agents for peripheral ulcerative keratitis (PUK) resulting from other causes.

For clarification, the extraocular manifestations of Crohn disease for each patient were controlled solely by the use of infliximab without additional therapeutic drugs after adequate dosing was achieved. In one patient, azathioprine was used to delay the formation of antimurine antibodies against infliximab. Although ocular and gastrointestinal activity was noted to have some correlation in our patients, as has been noted previously in the literature, the peripheral ulcerative keratitis was more resistant to therapy than their systemic manifestations. This suggests either that PUK may be a more severe manifestation of Crohn disease or, as in other disease processes, is either more easily recognized or causes greater disability in the eye at comparable levels of inflammation asymptomatic in other organ systems.

Regarding the dose and duration of previous therapy, these were managed by gastroenterologists before the patients’ referrals to our centers. Most of the known details are included in the article. The authors respectfully disagree with the suggestion that the PUK in these patients necessarily would have responded to adequate doses of other immunosuppressives. A more clinically relevant and more accurate term for any medication, but especially immunosuppressives, is maximally tolerated dose . Specifically, Patient 1, in addition to traditional conservative therapy, had received a trial of cyclophosphamide without effect and manifested blood glucose levels at moderate doses of systemic prednisone (30 mg/day) in excess of 500 mg/dL, resulting in diabetic ketoacidosis, and was under consideration for other alkylating agents. This patient was the subject of a multidisciplinary consultation taking into account all previous therapy, which concluded that other options for treatment had failed. Patient 2 had multiple corneal perforations despite long-term use of mycophenolate and was intolerant of salicylates and azathioprine. The overall medical condition of Patient 3 was a contraindication to any other systemic immunosuppressants, making infliximab the only option after only a partial response to systemic prednisone (60 mg/day). Although the authors agree that, in general, other forms of immunosuppression that are less costly might have controlled or maintained the sequelae of Crohn disease, these treatments failed, were not tolerated, or would not have acted sufficiently rapidly to prevent corneal perforation in these 3 patients.

Regarding inadequate control of PUK by infliximab, the reader should note that this also was addressed in the article. The exacerbations in Patient 1 occurred because therapy was administered only every 3 months, the recommended dosing schedule for systemic Crohn disease at the time. This illustrated the effective control of PUK when the drug was administered, but also highlighted what other investigators have found in that monthly dosing is more effective in controlling other forms of ocular disease. The lamellar keratoplasties performed in Patient 2 were elective, to reinforce areas that previously had thinned either when the patient was not receiving therapy or when the patient was noncompliant with the dosing regimen. No activity was noted when this patient received therapy every 4 to 6 weeks. Relapse or remission rates would be difficult to apply to any of these patients because of their variable and often suboptimal dosing. Further, the photographs presented are representative of the PUK seen in all 3 patients. Photographs of the remaining Patient 3 were of poor quality and would have added little to the manuscript.

Most of the known complications of tumor necrosis factor α inhibitors were listed in the article, including the concern of the correspondent, demyelinating disease. It should be noted that 2 of our patients were African American. Regardless, to our knowledge, other than a detailed history, no other screening tests for demyelinating disease currently are recommended before the use of infliximab, but clearly the drug should not be used in patients manifesting or developing these symptoms. Infectious complications are far more common, and screening and vigilance for infectious disorders is, of course, recommended.

Finally, the purpose of this article was not to evaluate the merits of infliximab as a viable long-term therapy for Crohn disease, but rather to report its acute and intermediate efficacy in the management of related PUK in the setting of failure of other interventions. Although control of the PUK in 2 of these patients consisted of extended use of biologic agents, the lack of long-term data was emphasized prominently in the Discussion, as well as the abstract, and should be difficult to misinterpret otherwise. It should be noted, however, that infliximab is an approved drug for Crohn disease and is used as such in the United States. We welcome your feedback and experience in treating these very challenging patients, recognizing that preservation of function often requires medications with higher risk profiles.

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Jan 12, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Reply

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