Multiple studies have shown that intratympanic (IT) drug therapy can be safe and effective for treating idiopathic sudden sensorineural hearing loss (ISSNHL) in adults. However, beyond those broad outcomes, the literature gets a bit opaque. Among the management issues that lack consensus among researchers are optimal patient selection, the best dosage and duration of therapy and the most effective drugs to use. And, while new ISSNHL treatment guidelines have shed some light on the role IT drug therapy should play in treating the condition, questions—and controversies—still remain.
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January 2013To gain more insight into how clinicians can interpret these results and use IT drug therapy optimally in their ISSHNL patients, ENTtoday spoke with several leading experts, including Richard K. Gurgel, MD, assistant professor in the division of otolaryngology-head and neck surgery at the University of Utah Health Care in Salt Lake City, who has extensive practice experience offering IT drug therapy to his patients with the disorder.
To best understand how and why IT drugs work, it is necessary to realize that “the term ‘intratympanic’ is something of a misnomer because it only describes the route of administration,” Dr. Gurgel told ENTtoday. “What we’re really accomplishing with this modality is inner-ear perfusion of medications into the inner ear via the transtympanic route.”
Before the advent of this approach, “there was no reliable method for altering the pathophysiology of the inner ear without destroying it or obliterating its normal function,” he said. With IT drug therapy, medication can be injected into the middle ear space, where it then travels by diffusion into the inner ear and acts upon structures that govern hearing. “This really is a very elegant, compelling modality,” Dr. Gurgel said, adding that it also has rigorous science to support it. In one study, researchers found that perilymph steroid concentrations were significantly higher after IT steroid therapy than after systemic steroid administration (Laryngoscope. 1999;109(7, Pt 2):1-17).
Impact on Disease
In reviewing the literature on the impact IT drug therapy has on actual disease, a less clear picture emerges, said Dr. Gurgel. “Most clinical studies are retrospective, single-institution studies with small patient numbers lacking adequate controls. The design, outcome measures and efficacy results of most studies tend to be all over the map.”
But there are some studies that do offer some useful insights, he added. He pointed to a 2011 study by Rauch and colleagues published in JAMA that he feels is one of the best-designed trials of its type. The prospective, randomized study compared oral versus IT steroid therapy for ISSNHL and found that both modalities were equivalent in the amount of improvement they achieved in final pure tone average (PTA), word recognition scores and other key measurements of hearing recovery (2011;305:2071-2079).
Interpreting the results of the study, Dr. Gurgel said. “Since IT drug therapy was noninferior to oral steroids, we are not doing a disservice to our patients if we offer it to them as an option, especially if they can’t tolerate the side effects of systemic steroids.”
Combination Therapy
Side effects of systemic therapy are only one aspect of care that clinicians will need to discuss with patients who present with sudden hearing loss; choice of therapy also needs to be explored, Dr. Gurgel said. “I do offer IT steroid injections to these patients but, frankly, many patients opt not to have it because they feel somewhat uncomfortable having something injected into their ear,” he said. “On the other side of the spectrum, I have patients who are so devastated by their sudden hearing loss that they are willing to try anything.” For those patients, he noted, combination therapy with systemic and IT steroids is another viable option.
There is evidence to support combination therapy but, again, the data are equivocal. In one positive study, a combination of a high-dose prednisone taper with IT steroids yielded a partial or complete hearing recovery in 14 of 16 patients (Otol Neurotol 2008;29:453-460). But, in another study, there was no statistically significant difference in hearing recovery as a result of combination therapy vs. steroids alone (Laryngoscope. 2008;118:279-282).
Those divergent results should not obscure the fact that combination therapy has a definite role in the management of ISSNHL, Dr. Gurgel noted. David S. Haynes, MD, professor in the department of otolaryngology/The Otology Group of Vanderbilt in Nashville, Tenn., echoed that view. “Most clinicians would opt for the combination approach—it’s what I would ask for,” he said. The main driver of that decision, he noted, is the fact that “we don’t fully understand what causes sudden hearing loss. Is it inflammation? An electrolyte dysfunction of the cochlea? A blood flow phenomenon? With all of those multifactorial processes occurring, I’d want a combined approach to cover all potential [causes].”
Having said that, however, Dr. Haynes said that he generally tends to take a more conservative approach to managing patients with ISSNHL than some of his colleagues. As a result, for one important consideration—whether to use IT steroids as initial or salvage therapy (i.e., after a patient has not responded to oral steroids or another treatment)—he comes down on the side of salvage. “If a patient persists with a two-day history of sudden hearing loss, I probably would not inject him or her right away, especially as we see patients improve spontaneously or with systemic therapy,” he said. “So my first-line approach is usually to tell patients that a week of systemic steroids is worth a try before injecting the ear. If systemic therapy fails, then we would certainly consider IT salvage therapy. We want to put patients in the best position to recover their hearing.”
Dr. Haynes is the lead author of a study that is often cited as evidence that IT steroid therapy can be an effective salvage treatment for patients with ISSNHL (Laryngoscope. 2006;117:3-15). In the study, 16 of 40 ISSNHL patients who had failed systemic steroid therapy achieved “modest” benefits after IT steroid injections. The response was based on patients showing any gain in PTA and speech reception threshold, Dr. Haynes said. But when a 20-db improvement in PTA or a 20 percent improvement in speech discrimination score was used as the criteria for success, the response rate fell to 27.5 percent.
“These were hardly dramatic results,” Dr. Haynes said. But in the intervening years, his own clinical experience, additional studies and new treatment guidelines on sudden hearing loss from the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) have helped clarify some of the issues surrounding both systemic and IT steroid therapy (Otolaryngol Head Neck Surg. 2012;146:3 suppl S1-S35). Unfortunately, he said, those guidelines don’t appear to have resolved all the issues affecting treatment choice.
AAO-HNS Guidelines
Seth Schwartz, MD, MPH, neurotologist in the department of otolaryngology at Virginia Mason Medical Center in Seattle, who co-authored the new AAO-HNS guidelines, acknowledged that the recommendations that addressed systemic and IT steroids for SSHNL led to some confusion.
“The main criticism we heard was that there is some inherent lack of logic in how we worded those recommendations: specifically, our stating that clinicians may offer steroids as initial therapy to patients with ISSNHL, but that IT steroids should be used for salvage therapy,” he said. “I understand that position—why would a drug work for salvage when it failed a patient initially? Despite that, the strength of those recommendations was based on the best available data.”
The reason for the somewhat weaker wording on the initial steroid recommendation—and the lack of specificity on whether initial therapy should be systemic or IT—is the divergent nature of the data, Dr. Schwartz said. In reviewing the literature, he said, “we found studies saying that initial steroids are better than placebo, and also studies that showed no difference between placebo and steroids.”
The use of steroids as initial therapy for ISSNHL “has always been something of a sacred cow among ENT physicians,” he added. “So it is hard to challenge that. But there’s logic in our choice of wording: The harm to patients from sudden hearing loss is so great, and the risk from steroids is fairly low, that we deemed it worthwhile to characterize steroids as an option, even though the data are very soft on using it as initial therapy.”
Dr. Gurgel said that, given the divergent nature of the data on IT drug therapy for ISSNHL, the guidelines struck the right balance in their recommendations. As for which particular regimen to use, he said, “I try to use evidence to guide what we do clinically, so for me the Rauch study offers a nice protocol where patients were given 1 mL of 40-mg/mL methylprednisolone, in four injections over two weeks. There are certainly other regimens that are also effective.”
However, given the lack of comparative data and consensus on specific regimens, timing and dosage, he said, “at the end of the day, patient preference and your own clinical experience will often have to guide you towards the best treatment option for a given patient.”