No Link Between Oral Fluoroquinolones, Uveitis in Large Study

Jennifer Garcia

November 05, 2015

There is no association between the use of oral fluoroquinolones and an increased risk for uveitis, according to the results of a retrospective cohort study that included more than 4 million patients.

"Given the systemic illness findings in this study, it is more probable that fluoroquinolone use is a marker that identifies a group of patients who are more likely to develop a disease associated with uveitis rather than causing uveitis," write Harpal Singh Sandhu, MD, from the Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, and colleagues.

The researchers published their findings in an article published online October 29 in JAMA Ophthalmology.

Dr Sandhu and colleagues evaluated medical claims data collected between January 1, 2000, and January 30, 2013, by a large US national insurer. They identified 843,854 patients who received a fluoroquinolone and 3,543,797 patients who received a β-lactam during that time. Patients were excluded if they had any previous diagnosis of uveitis or if they had any systemic disease known to be associated with uveitis. In the fluoroquinolone group, the mean age was 53.2 years, and 58.1% of the patients were female; in the β-lactam group, the mean age was 37.1 years, and 51.7% of the patients were female.

The researchers found no increased risk for the development of uveitis at 30-, 60-, and 90-day follow-up visits after controlling for age, sex, and race (hazard ratio [HR] range, 0.96 [95% confidence interval (CI), 0.82 - 1.13] to 1.05 [95% CI, 0.95 - 1.16]; P > .38 for all comparisons). A small increase in uveitis in the fluoroquinolone cohort was noted at 365 days in the multivariate analysis (HR, 1.11; 95% CI, 1.05-1.17; P < .001).

Of the fluoroquinolones used, only moxifloxacin showed an association at every point (HR at 30 days, 1.75; 95% CI, 1.28 - 2.37; HR at 365 days, 1.47; 95% CI, 1.30 - 1.65; P < .001 for all comparisons).

"Prior to this study, the association between fluoroquinolones and uveitis was unclear, with some studies suggesting that there was a significant link," said Dr Sandhu in an interview with Medscape Medical News. "I think it's fair to say that there is little association, and that which does exist is small."

Disease, Not Drug, Likely the Reason for Increased Uveitis Risk

The researchers posit that indication bias may in fact be the reason for the perceived increase in risk for uveitis among patients treated with oral fluoroquinolones. As part of a secondary analysis, the researchers found that any oral fluoroquinolone use was significantly associated with an incident diagnosis of a known uveitis-associated systemic illness at all times (HR range, 1.46 - 1.96; 95% CI, 1.42 - 2.07; P < .001 for all comparisons).

"We interpret these data to mean that fluoroquinolones are unlikely to cause uveitis; rather, a prescription for a fluoroquinolone is a marker of patients with some broader immune dysregulation that predisposes them to an infection for which a fluoroquinolone would be prescribed, which is then followed by uveitis," the study authors write.

The researchers acknowledge study limitations such as the fact that an exact diagnosis for which the patient was prescribed antibiotics was not available from medical claims billing data. In addition, these data only included outpatient prescriptions, and there was no way to confirm that patients completed their antibiotic course.

In an invited commentary, also published in JAMA Ophthalmology, Farzin Forooghian, MD, FRCSC, from the University of British Columbia, St Paul's Hospital, Vancouver, Canada, notes that there are certain factors that need to be considered when evaluating information derived from medical claims database research, including using proper controls, accounting for confounding bias, and replication and validation of the results.

Dr Sandhu agreed on the inherent limitations in using medical claims database data.

"Dr Forooghian and I are of one mind on this subject," he said. "Furthermore, I wholeheartedly agree that reproducibility is a hallmark of good science."

"Controlling with another antibiotic with similar indications, beta-lactams, and excluding all patients with a known diagnosis of one of the 18 uveitis-associated systemic diseases strengthened the study considerably," he told Medscape Medical News.

When asked by Medscape Medical News whether he felt that the study findings were accurate, given the limitations of this kind of research, Dr Forooghian responded: "I do not feel that the [previously] reported association between fluoroquinolones and uveitis is real." Reports of this association are likely the result of confounding bias, which was not accounted for in previous studies, he said.

Funding for this study was provided by the National Institutes of Health, Research to Prevent Blindness, and the Paul and Evanina Mackall Foundation. The authors and editorialist have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online October 29, 2015. Article abstract, Editorial extract

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