ARTICLE IN BRIEF
In the first major randomized controlled trial testing the benefit of epidural steroid injections (ESIs) for spinal stenosis, investigators reported that ESIs plus lidocaine offered minimal or no short-term benefit for spinal stenosis compared with epidural injections of lidocaine alone.
Epidural injections of glucocorticoids plus lidocaine offered minimal or no short-term benefit for spinal stenosis compared with epidural injections of lidocaine alone, according to a report in the July 3 New England Journal of Medicine (NEJM).
This finding is the result of the first major randomized controlled trial testing the benefit of an intervention — epidural steroid injections (ESI) — that has been widely adopted for spinal stenosis despite minimal or no evidence for its effectiveness and a greater risk of adverse events. The effectiveness of lidocaine alone was a somewhat surprising outcome from the study, researchers said.
“Going into the study the team thought there was not sufficient or robust evidence that glucocorticoid injections provided a benefit, and we believed there was enough uncertainty to justify a randomized controlled trial,” said the study co-author Jeffrey Jarvik, MD, a professor of radiology, neurological surgery, and health services, and director of the Comparative Effectiveness, Cost and Outcomes Research Center at the University of Washington.
“We were surprised at how well the lidocaine-only group did,” Dr. Jarvik said. “We should emphasize that both groups improved over time, but the steroid group did not improve substantially more than the lidocaine group while also having more adverse events.”
The multisite trial — led by Janna L. Friedly, MD, and Dr. Jarvik — randomly assigned 400 patients, who had lumbar central spinal stenosis and moderate-to-severe leg pain and disability, to receive epidural injections of glucocorticoids plus lidocaine, or lidocaine alone. The patients received one or two injections before the primary outcome evaluation performed six weeks after randomization and the first injection. The primary outcomes were the score on the Roland Morris Disability Questionnaire (RMDQ) — in which scores range from 0 to 24, with higher scores indicating greater physical disability — and the intensity of leg pain on a rating scale from 0 to 10, with 0 indicating no pain and 10 indicating “pain as bad as you can imagine.”
Twenty-six board-certified physicians with expertise in administering epidural glucocorticoid injections performed the procedures, and were instructed to choose the injection level 1 spinal level below the maximal canal stenosis for interlaminar injections, and at the root level where symptoms were most pronounced for transforaminal injections. The physician chose the approach — transforaminal or interlaminar — which remained consistent with subsequent injections for each patient. The glucocorticoid injectable solution consisted of 1-3 ml of 0.25 percent to 1 percent lidocaine followed by 1-3 ml of triamcinolone (60 to 120 mg), betamethasone (6-12 mg), dexamethasone (8-10 mg), or methylprednisolone (60-120 mg).
At six weeks, there were no significant between-group differences in the RMDQ score or the intensity of leg pain. A secondary subgroup analysis with stratification according to type of injection —interlaminar or transforaminal — likewise showed no significant differences at six weeks.
Patients in the steroid group did slightly better at three weeks, but the benefit over lidocaine-only did not persist to six weeks. Interestingly, the glucocorticoid-lidocaine group had more improvement with respect to symptoms of depression on the Patient Health Questionnaire Depression Scale. On the Swiss Spinal Stenosis Questionnaire, 67 percent of patients who received glucocorticoids plus lidocaine reported being very or somewhat satisfied with their treatment, as compared with 54 percent of those who received lidocaine alone.
Dr. Jarvik noted that at both three and six weeks, a significantly higher proportion of patients in the glucocorticoid-lidocaine group than in the lidocaine-alone group had morning serum cortisol levels of less than 3 μg per deciliter or less than 10 μg per deciliter. One hypothesis for the greater satisfaction among the steroid group is that the systemic effect of the glucocorticoid, as evidenced by suppression of cortisol, improves feelings of overall well being, he said.
At the same time, 21.5 percent in the glucocorticoid-lidocaine group and 15.5 percent in the lidocaine-alone group reported adverse events. There were more adverse events on average per person in the glucocorticoid-lidocaine group than in the lidocaine-alone group.
“This is an interesting study of an important clinical topic,” Kris Radcliff, MD, of the Rothman Institute at Jefferson University, told Neurology Today. “These findings are somewhat surprising given the widespread usage of ESI. However, most of the previous studies on ESI have evaluated patients with disk herniation, not purely spinal stenosis.”
Dr. Radcliff noted that he and his colleagues found a similar result in a subgroup analysis of the Spine Patient Outcomes Research Trial; patients with spinal stenosis who received epidural steroid injections had less improvement compared with patients who did not receive an ESI.
But, Dr. Radcliff said the current study — as a prospective, randomized, double-blinded trial— is statistically more rigorous, less susceptible to sample size errors and bias, and also stratifies outcome by injection type. “I believe that these findings may lead clinicians to re-evaluate the indications for ESI in some patients with central stenosis and neurogenic claudication,” he said. “However there may be a benefit of epidurals for patients with other types of pathology, such as spondylolisthesis, as those diagnoses were outside of the scope of this study. I would have also liked to have seen longer term follow-up.”
In a June 18 online edition of Neurology Clinical Practice, Gary Franklin, MD, MPH, FAAN, and John Markman, MD, FAAN, addressed the subject of epidural injections for spinal pain in an editorial published prior to the publication of the NEJM study. “Epidural steroid injections are the most highly studied of the therapeutic spinal injection types,” they wrote. “In a patient with a primarily painful lumbar radicular pain but in the absence of signs of a deteriorating nerve root, this type of injection may seem to be an attractive treatment alternative.” They noted that systematic reviews from the AAN (2007) and the American Pain Society (2009) have produced “fair evidence [that] suggests short-term pain relief.”
But, Drs. Franklin and Markman added: “As with other therapies for chronic low back pain, including behavioral approaches, there is minimal evidence for long-term functional benefit...A relatively robust cost-utility analysis conducted in the United Kingdom stressed that an epidural steroid injection is not a stand-alone therapy. Rather, the authors recommended that such intervention should be viewed as part of a package of rehabilitative care, where a coherent analgesic strategy is provided, and potential psychosocial barriers to rehabilitation are addressed in a systematic fashion.”
In comments to Neurology Today about the NEJM study, Dr. Franklin, a neurologist who is a research professor in the environmental and occupational health sciences at the University of Washington, said ESI for spinal stenosis “would seem to make the most sense biologically,” but added that even here, the NEJM study “appears to indicate that there really isn't a sufficient benefit.”
Dr. Jarvik said he hopes the NEJM study will help inform discussions between physicians and patients as they weigh the risks and benefits of treatment options. “There wasn't great data before this on which to make an evidence-based decision,” he said. “Now the conversation can be founded on good data suggesting that there is a very small, not clinically significant benefit [to steroid injection] that probably won't last up to six weeks, while at the same time there is a higher likelihood of adverse events than with lidocaine alone.”
“The bottom line is that patients need to weigh the risks and benefits in an informed conversation with their physician,” Dr. Jarvik said.