Original article
Initiation of Anti-TNF Therapy and the Risk of Optic Neuritis: From the Safety Assessment of Biologic ThERapy (SABER) Study

https://doi.org/10.1016/j.ajo.2012.06.023Get rights and content

Purpose

To evaluate the incidence of optic neuritis (ON) in patients using anti–tumor necrosis factor (TNF) alpha therapy.

Design

Retrospective, population-based cohort study.

Methods

We identified new users of anti-TNF therapy (etanercept, infliximab, or adalimumab) or nonbiologic disease-modifying antirheumatic drugs (DMARDs) during 2000–2007 from the following data sources: Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and National Medicaid/Medicare. Within this cohort, we used validated algorithms to identify ON cases occurring after onset of new drug exposure. We then calculated and compared ON incidence rates between exposure groups.

Results

We identified 61 227 eligible inflammatory disease patients with either new anti-TNF or new nonbiologic DMARD use. Among this cohort, we found 3 ON cases among anti-TNF new users, occurring a median of 123 days (range, 37–221 days) after anti-TNF start. The crude incidence rate of ON across all disease indications among anti-TNF new users was 10.4 (95% CI 3.3–32.2) cases per 100 000 person-years. In a sensitivity analysis considering current or past anti-TNF or DMARD use, we identified a total of 6 ON cases: 3 among anti-TNF users and 3 among DMARD users. Crude ON rates were similar among anti-TNF and DMARD groups: 4.5 (95% CI 1.4–13.8) and 5.4 (95% CI 1.7–16.6) per 100 000 person-years, respectively.

Conclusion

Optic neuritis is rare among those who initiate anti-TNF therapy and occurs with similar frequency among those with nonbiologic DMARD exposure.

Section snippets

National Registry of Drug-Induced Ocular Side Effects

The National Registry of Drug-Induced Ocular Side Effects passively collects reports of ocular toxic drug events from physicians within the United States and abroad.3 In addition, the registry is linked with the Food and Drug Administration's (FDA) Medwatch system (Rockville, Maryland, USA) and the World Health Organization's (WHO) Spontaneous Event Reporting Systems (Uppsala, Sweden) such that events reported to all 3 systems are retrievable within the National Registry of Drug-Induced Ocular

National Registry of Drug-Induced Ocular Side Effects

From the national registry collecting passively reported data, we identified 358 reports of optic neuritis occurring in association with anti-TNF therapy. Seventy-five percent were female, median age 44 years (range, 6–78 years), with median time between anti-TNF start and diagnosis of 182 days (range, 2–388 days). Cases were most numerous with etanercept (n = 169), with fewer reported with monoclonal antibodies infliximab (n = 122), adalimumab (n = 55), golimumab or certolizumab (n = 5), or

Discussion

Within SABER, a large US multi-institutional research initiative, we performed a large population-based cohort study specifically examining optic neuritis incidence in patients starting biologic therapy with anti-TNF agents. We found the incidence of optic neuritis to be low in this group, approximately 5–10 per 100 000 patient-years, and comparable to published rates from other population-based studies estimating the incidence of optic neuritis.1 Importantly, optic neuritis rates were not

Kevin L. Winthrop MD, MPH, is Assistant Professor of Infectious Diseases, Ophthalmology, and Public Health and Preventative Medicine at Oregon Health and Science University, Portland, Oregon. He is an infectious disease epidemiologist whose research and clinical interests include onchocerciasis elimination, as well as drug safety and pharmacovigilance with specific focus upon the epidemiology, prevention, and therapy of serious infections that occur in patients with autoimmune inflammatory

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Kevin L. Winthrop MD, MPH, is Assistant Professor of Infectious Diseases, Ophthalmology, and Public Health and Preventative Medicine at Oregon Health and Science University, Portland, Oregon. He is an infectious disease epidemiologist whose research and clinical interests include onchocerciasis elimination, as well as drug safety and pharmacovigilance with specific focus upon the epidemiology, prevention, and therapy of serious infections that occur in patients with autoimmune inflammatory disease.

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