ARTICLE IN BRIEF
In the first major randomized controlled trial testing the benefit of oral steroids in patients with acute sciatica due to a herniated disk, investigators reported that oral steroids provided moderate improvement in function and no reduction in pain.
The oral steroid prednisone offered no reduction in pain and only a modest improvement in function for patients with acute radiculopathy due to a herniated disk, according to a new study.
The study, published in the May 19 edition of the Journal of the American Medical Association (JAMA), was the first appropriately powered trial to examine the effect of oral steroids in this patient population, the researchers wrote.
Previous studies have shown that surgical interventions do not necessarily lead to improvement in patients with acute sciatica, lead study author Harley Goldberg, DO, director of spine care at Kaiser Permanente in San Jose, CA, told Neurology Today. “In this trial, we wanted to see if another non-surgical option or non-interventional option would be effective.”
The findings were unexpected, according to Dr. Goldberg. The researchers had hoped to see more improvement in patients taking the oral steroids, but “found that although patients continued to do better relatively quickly, there was no difference whether they were taking the oral steroid or the placebo. What we were really seeing was the natural history of the disease, and that was a surprise.”
STUDY METHODOLOGY, FINDINGS
In a randomized, controlled, double-blind clinical trial, 269 patients who had experienced radicular pain for up to three months were assigned to prednisone on a tapering 15-day course (60 mg, 40 mg, and 20 mg for five days each) or a placebo.
Eligible participants had a score of 30 or higher on the Oswestry Disability Index (ODI) — a score of 100 indicates the most severe disability — and had a herniated disk confirmed by magnetic resonance imaging (MRI). The investigators excluded patients who had radicular pain more than three months prior, previous lumbar surgery, oral or epidural steroid treatment in the prior three months, and/or ongoing litigation or workers' compensation claims.
Although the investigators initially included leg pain that extended below the knee as a criterion for participation in the trial, they eliminated that requirement after 14 months to improve recruitment.
Participants were seen in the clinic at three weeks and 24 weeks after randomization, and were telephoned at six, 12, and 52 weeks to see how they were faring.
The primary outcome measure for the trial was change in ODI after three weeks. The group of 181 patients receiving steroid treatment had an adjusted mean 6.4-point (p=0.006) greater improvement in ODI scores at three weeks than the placebo group and a mean 7.4-point (p=0.005) greater improvement at one year. The difference in pain reduction was not significant, however.
After one year, there were no differences in surgery rates among the two groups. Adverse events were more common in the steroid group (49.2 percent vs. 23.9 percent; p<0.001), but the majority of these were minor.
“The main takeaway is that in aggregate for all of these patients, the use of oral steroids did not actually make a significant difference in their pain, though it did make a modest difference in their functional capacity as measured through the ODI,” Dr. Goldberg said.
Importantly, these findings provide the practicing physician with better data for an informed conversation with patients, he said. “So when deciding between surgery, epidural steroids, oral steroids, non-steroidals, or other treatment options, we have more information now on how to hold oral steroids in that context. I don't think it slams the door on the use of oral steroids,” Dr. Goldberg said.
Currently, the study authors are looking into their data set for clues about which patients were more likely to improve with oral steroids — for example, whether or not different disk morphology had any effect on patient benefit in the treatment groups.
In future studies, Dr. Goldberg said it would also be helpful to do a head-to-head comparison of epidural steroids versus oral steroids, as well as a similarly randomized trial of oral steroids versus placebo among acute radiculopathy patients.
Spinal care experts told Neurology Today that these findings were largely compatible with their own clinical observations. “Most experienced neurologists have recognized a lack of a striking benefit from this treatment modality, but it has been used as a limited-risk tool to bide time waiting for spontaneous improvement in symptoms,” said Kerry H. Levin, MD, chairman of the department of neurology and director of the Neuromuscular Center at the Cleveland Clinic.
What was surprising, however, said J. D. Bartleson, MD, an associate professor of neurology at the Mayo Clinic in Rochester, MN, was the finding that prednisone therapy provided some improvement in function but not pain. “Since there was no observational group, we do not know if there was a significant placebo effect,” he added.
A notable weakness of the trial, commentators said, was the inclusion criteria. “The criterion of a positive Straight Leg Raise sign was dropped due to difficulty finding enough patients having this abnormality. Inclusion criteria for ‘acute radiculopathy’ included up to three months of symptoms, whereas most neurologists consider acute radiculopathy to be up to about one month,” explained Dr. Levin. After a month of symptoms, he said, many patients will experience improvement from approaches including non-steroidal anti-inflammatory drugs, mobilization, and avoidance of pain-producing activities, even without the use of corticosteroids.
Overall, he said, “it is still not clear how beneficial oral corticosteroid therapy might be in a more selected patient population with shorter-duration symptoms and more specific neurologic features of radiculopathy.”
Miroslav Backonja, MD, the medical director of the PRAHS Lifetree Center for Neuroscience Research and emeritus professor of neurology at the University of Wisconsin, told Neurology Today that these results were neither surprising nor particularly illuminating. “What clinicians usually struggle with is how to get these patients comfortable through the first couple of weeks or months and relieve their pain. This trial shows that oral steroids are not able to help with that more than what happens in the natural course of this clinical challenge.”
Despite the limitations, Dr. Bartleson said, the trial suggests that oral steroids could be offered to patients with acute radiculopathy instead of an epidural steroid injection in order to avoid the costs of injection and MRI, reduce the risks associated with needle procedures on the spine, and avoid radiation exposure from fluoroscopy during the procedure. Ultimately, he said, “the decision will be influenced by the severity of symptoms, other medical problems, and patient preference.”
Additionally, although the study reaffirmed that a brief course of oral steroids did not prevent surgery, what remains unknown is whether it would enable patients to avoid spinal injections altogether, Dr. Bartleson said. “It would be important to know if there is a significant placebo effect when treating lumbar radiculopathy with oral corticosteroids and other therapies. The timing of a course of oral corticosteroids — for example, whether giving them sooner is better — as well as the specific drug, the specific dose, and the duration of therapy are all unknown and worthy of study.”
A larger problem with the design and interpretation of radiculopathy studies that needs to be addressed, Dr. Backonja said, is the inconsistency of diagnostic criteria and outcome measures used. “Radiculopathy spans so many specialties — everything from neurosurgery to anesthesia to rehab to neurology to primary care to rheumatology — so everyone brings their own tools and biases, and results are all over the place.” There needs to be more collaboration and standardization in order for this research to be more effective and translatable, and to allow researchers to learn more from studies even when results are not clearly positive, he said.