Are ONTT recommendations understood?

Physicians let patients decide whether to receive treatment.

Ophthalmologists and neurologists may have changed their use of steroids to treat optic neuritis without fully understanding the results of the most definitive clinical trial on the subject to date.

However, the subtleties that researchers believe their peers may have missed are not negatively affecting the treatment of patients, who would likely receive the same regimen although for different reasons.

Researchers reported in the November 1999 issue of Ophthalmology that the Optic Neuritis Treatment Trial (ONTT) caused physicians to reduce their prior practice of prescribing oral prednisone.

However, researchers wrote, “Ophthalmologists and neurologists have changed some of their practices without fully understanding the results of the ONTT.”

Nearly all of the physicians had reduced their use of oral prednisone alone and were including IV methylprednisolone as part of their regimen. However, many physicians incorrectly believe that IV methylprednisolone improves visual outcomes, while the ONTT concluded only that it quickened visual recovery.

Study author Jonathan D. Trobe, MD, told Ocular Surgery News that neuro-ophthalmologists and neurologists have convincingly stopped prescribing oral prednisone alone. But he added that he does not push for any one treatment regimen in his own practice.

ONTT results

The ONTT randomized 457 patients with acute optic neuritis into three groups: patients who received treatment with prednisone for 2 weeks; patients who received IV methylprednisolone for 3 days and prednisone for 11 days; and a control group.

ONTT researchers concluded that prednisone alone not only offered no benefit, but it doubled the recurrence rate. The IV pretreatment delayed other neurologic events and quickened visual recovery.

ONTT had a few important findings. Perhaps the most important one related to changing clinical practice was that oral prednisone did not improve recovery compared with placebo. Also, patients treated with oral prednisone seemed to have a higher rate of recurrence of optic neuritis. Beyond that, there was no benefit that was related to treatment.

According to Roy W. Beck, MD, PhD, the primary investigator for ONTT, “If we were to rate the conclusions from the ONTT in terms of how definitive we were with conclusions, the lack of benefit from oral prednisone in the usual dose was the only definitive conclusion. The numbers show that there has been a pretty substantial impact on changing clinical practice.”

He added that ONTT researchers concluded that IV methylprednisolone tended to speed recovery, but there did not appear to be a long-term benefit from treatment. There was, however, a rationale to consider treatment based on getting the patient better faster.

Before ONTT, less than 10% of ophthalmologists were using IV methylprednisolone to treat optic neuritis, but after the study, a substantial percentage did so.

“That decision whether to treat with IV methylprednisolone or no treatment at all is left up to the physician to decide with the patient,” he said.

Adjusting patterns

Researchers following up on ONTT results mailed surveys to 987 ophthalmologists and 900 neurologists to question their regimen to manage optic neuritis before the ONTT results were tabulated and how that regimen changed since the study was conducted. They received responses from 202 ophthalmologists and 244 neurologists, for a response rate of 47%.

Researchers reported in Ophthalmology that after the ONTT first published its results, 84% of ophthalmologists and 72% of neurologists changed some aspect of treatment. Most physicians who changed their regimen reduced how often they gave only oral prednisone.

Of those who changed their practice patterns, 67% of ophthalmologists and 82% of neurologists began to prescribe IV methylprednisolone more often.

Now, 74% of ophthalmologists and 68% of neurologists never prescribe prednisone alone, according to the article. Of the respondents, 81% of neurologists use IV methylprednisolone in more than one-half of their patients. Also, 40% of ophthalmologists use it in more than one-half of their patients. They did so in the belief that it would improve visual outcomes.

In the study, 53% said IV methylprednisolone was “very important” as a reason to switch regimens. Also, 65% said it was very important as an effective way to hasten visual recovery and 53% said it was very important as a way to reduce future neurologic events of multiple sclerosis (MS).

But the authors concluded that practitioners changed their practice habits without fully understanding the results.

They wrote, “Nearly three-fourths of neurologists and half of ophthalmologists say they are embracing the intravenous regimen as the most effective way to improve final visual outcome. Yet the ONTT publications clearly state that no treatment influences 1-year visual outcome.”

Primary study results led to a dramatic change in usual clinical practice. Before ONTT, IV prednisone was used just a little. The treatment was almost always oral.

Now the entire medical community bought the idea that prednisone should not be used alone on optic neuritis. An overwhelming number used it as a “chaser” to IV methylprednisolone, Dr. Trobe said.

He gives his own patients a choice between treatment or no treatment. Steroids may reduce the incidence of a future neurological event for 2 years, “and under those circumstances, they should be treated,” he said. “But they should understand that it’s only temporary, and that the final result beyond 2 years is no different in terms of MS.”

Subtleties of practice

According to Barrett Katz, MD, MBA, Neuro-Sciences Section Editor of Ocular Surgery News Editorial Board, subtleties of the study are sometimes overlooked.

In ONTT, patients were enrolled within 8 days of symptoms, and the study put patients in the hospital, treating them with IV steroids four times per day for 3 days.

In their clinical practice, many ophthalmologists treat once per day on an out patient basis.

“That’s not the way the study protocol administered IV treatment. So what many of us do clinically in administering IV steroids in one dose daily as an outpatient is not precisely the regimen employed in the ONTT,” said Dr. Katz, who also worked on the ONTT.

Patients also must understand that the recommendation to treat with IV steroids is not to improve the vision of the eye but to protect from future neurologic events.

Dr. Beck added that although there may be misconceptions about some aspects of treatment with methylprednisolone, it still does not mean that physicians do not understand ONTT results or are treating patients for the wrong reason.

“They may well have had that misconception that there’s long term benefit, but still we’re treating to get the patient better faster,” he said. “The fact that they had a misconception about the long term may not have had anything to do with why they decided to prescribe treatment or not, because their assumption about the short term was correct. I don’t think that can be distinguished based on the way the survey was conducted.”

Evidence-based medicine

According to Dr. Katz, several papers have been written summarizing the study and perhaps those need to be more widely disseminated. ONTT research had considered putting the study results on a laminated card.

He added that, in his own practice, he shares the results of the ONTT with his patients, who must ultimately decide whether to have a scan or to have IV steroids.

“Our job should be to share the evidence with the patient and let the patient work through their own decision making, help them where we have to and where we can,” he said. “It also speaks to how difficult it is to get to the clinician the evidence upon which people should be basing their practice habits.”

For Your Information:

• Barrett Katz, MD, is professor and chair of the Department of Ophthalmology, George Washington University School of Medicine, 2150 Pennsylvania Ave. NW, Ste. 2A, Washington, DC 20037; (202) 994-4048; fax: (202) 994-6209. Dr. Katz did not disclose whether he has a direct financial interest in any of the products mentioned in this article or if he is a paid consultant for any companies mentioned.
• Roy W. Beck, MD, PhD, is director of the Jaeb Center for Health Research, 3010 E. 138th Ave., Ste. 9, Tampa, FL 33612; (813) 975-8690; fax: (813) 975-8761. Dr. Beck has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Jonathan D. Trobe, MD, can be reached at the W.K. Kellogg Eye Center, 1000 Wall St., Ann Arbor, MI 48105; (734) 763-9147; fax: (734) 936-2340. Dr. Trobe has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Reference:

• The impact of the Optic Neuritis Treatment Trial on the practices of ophthalmologists and neurologists. Ophthalmology. 1999;106:2047-2053.