Anti-TNF Agents Recommended for Ocular Disease

Larry Hand

December 24, 2013

The antitumor necrosis factor alpha (TNF-α) biological agents infliximab and adalimumab are effective treatments for severe ocular inflammatory diseases, according to recommendations from the American Uveitis Society published online December 18 in Ophthalmology.

The recommendations support existing off-label prescribing of the medications and may help to get more of those prescriptions covered by insurance companies.

Grace Levy-Clark, MD, formerly from St. Luke's Cataract and Laser Institute, Tarpon Springs, Florida, currently from Vistakon Pharmaceuticals, Jacksonville, Florida, and colleagues conducted a systematic review of published studies and then made the recommendations based on grading of the studies. The researchers constituted a subcommittee of the executive committee of the American Uveitis Society.

The researchers reviewed about 400 studies from the past 15 years, through May 1, 2013, covering the 5 anti-TNF biological agents approved by the US Food and Drug Administration: etanercept, infliximab, adalimumab, golimumab, and certolizumab. All 5 are approved for treating autoimmune disorders, including rheumatoid arthritis, but not for ocular diseases. Golimumab and certolizumab, however, have not been in clinical use long enough to evaluate their effectiveness, so the recommendations are focused on the other 3 agents, the researches write.

The researchers found a "preponderance of published literature" documenting the use of infliximab to treat uveitis, but few studies addressing the comparative effectiveness of infliximab and adalimumab or which agent should be used as primary treatment. They did find, however, that published data suggest that etanercept has lower efficacy against some forms of uveitis than the other 2 agents.

"Perhaps the most unexpected finding was the consensus in the evidence that not all drugs in this class appear equally efficacious in treatment of uveitis," Russell N. Van Gelder, MD, PhD, senior author and director of the University of Washington Medicine Eye Institute in Seattle, wrote in an email to Medscape Medical News. "In particular, etanercept does not seem as effective in some uveitic conditions as adalimumab or infliximab."

5 Recommendations

The researchers made 5 recommendations for treatment of inflammatory disorders with clinical manifestations including, but not limited to, uveitis.

  1. Consider infliximab or adalimumab early in the management of patients with vision-threatening ocular manifestations of Behçet's disease, a multisystem disorder. (Strong recommendation)

  2. Consider infliximab or adalimumab as second-line therapy for children with vision-threatening uveitis secondary to juvenile idiopathic arthritis (JIA) when methotrexate therapy is ineffective or not tolerated. If tolerated, however, methotrexate therapy can be combined with infliximab. (Strong recommendation)

  3. Consider infliximab or "potentially" adalimumab as second-line therapy for patients with vision-threatening chronic uveitis from seronegative spondyloarthropathy. (Strong recommendation)

  4. Consider infliximab or adalimumab for patients with vision-threatening corticosteroid-dependent disease whose first-line therapy failed. (Discretionary recommendation)

  5. Consider infliximab or adalimumab before etanercept for treatment of ocular inflammatory disease. Consider switching patients currently taking etanercept to infliximab or adalimumab. (Strong recommendation)

Long Process

"This was a long process, taking over 2 years from start to finish," Dr. Van Gelder noted. "The field is moving quickly, and each time we revised, there were more important studies to add to this review."

He continued, "The challenge we face is that we are evaluating use of a class of drugs for a set of uncommon diseases. There is a paucity of randomized controlled trials. As such, we had to put together recommendations based on less rigorous primary evidence. However, we had little disagreement amongst the authors on the final recommendations."

The German Ophthalmological Society and the European League Against Rheumatism have made similar recommendations previously, but this is the first set of such recommendations for the United States.

Clinicians already use these biological agents off-label for treating uveitis, Dr. Van Gelder told Medscape Medical News. "These are expensive medications, and insurers frequently deny coverage for these agents, citing lack of evidence for their use. It is our hope that these guidelines, along with the extensive literature review underpinning them, will help clinicians in their quest to provide optimal medications for their patients"

Reflection of Current Practice

"I think the data pretty much reflect my experience," Wendy M. Smith, MD, assistant professor of ophthalmology and a uveitis expert at the Mayo Clinic in Rochester, Minnesota, told Medscape Medical News. "I work with rheumatologists to prescribe these medications for my patients. Hopefully it will be easier to get these medications approved by insurance companies."

She is proactive in getting her patients' medicines covered by insurance companies. "I usually write a letter, and I review the existing literature, and probably 8 or 9 times out of 10, I'm able to get it approved, but we usually have to appeal once or twice. Hopefully, this paper will help. I certainly will be including this paper among the papers that I cite, probably top on the list, although many of the conditions I treat are not yet among the strong recommendations."

Conditions manifesting as uveitis other than the ones in the recommendations are very rare and still lack data on causes and treatments, she said.

However, especially for Behçet's disease and JIA, the recommendations "will probably move people toward using these medications even faster. In particular, in JIA, already clinicians move quickly to the TNF inhibitors. I hope what it will do eventually for us clinically is more of us will do studies on those other conditions of uveitis where we don't have good data. This is a very good starting point, and it's a great paper summarizing the existing literature and also showing us where we still need to do more work."

This research was supported by the Burroughs-Wellcome Foundation and Research to Prevent Blindness. Dr. Levy-Clarke has reported being employed by Vistakon. Dr. Van Gelder has reported receiving financial support from Alcon Research Laboratories and Novartis. Three coauthors have reported serving as consultants to several pharmaceutical companies. The remaining coauthor and Dr. Smith have disclosed no relevant financial relationships.

Ophthalmology. Published online December 18, 2013. Abstract

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