Friday, March 15, 2013

Steroid Shots Fail for Pain - Again

InjectionA pair of recently reported clinical trials separately examined the benefits of corticosteroid injections for two very different painful musculoskeletal conditions: spinal stenosis and lateral epicondylalgia (“tennis elbow”). In neither case, compared with control groups, were the injections of help in relieving pain or improving function long-term. In fact, the injections may do more harm than good.

The first study examined the use of epidural steroid injections (ESI) in patients with lumbar spinal stenosis. Researchers compared outcomes in 69 patients with the disorder who received ESI within the first 3 months of enrollment with a group of 207 similar patients who did not receive such injections during that time period (no-ESI) [Radcliff et al. 2013]. Patients ranged in age from 53 to 75 years and were comparable in demographic and baseline clinical characteristics. All were participating in a larger long-term study, the Spine Patient Outcomes Research Trial, or SPORT.

The researchers hypothesized that patients who received ESI early during treatment might have improved clinical outcomes and a lower rate of crossover to surgery than patients in the no-ESI subgroup. However, writing in the journal Spine, they reported that patients receiving ESI had significantly less improvement  on various well-established scales to measure symptoms of leg and lower back pain — than those who did not have the injections.

Furthermore, among subjects who ultimately underwent surgical treatment, those in the ESI group had increased operative times and longer hospital stays. Averaged over 4 years, there was significantly less improvement in physical function and body pain measures among subjects in the ESI group whether or not they went on to have surgical treatment.

The researchers conclude that patients with lumbar spinal stenosis treated with ESI demonstrate significantly less improvement, whether treated surgically or nonsurgically over time. Therefore, despite the common treatment practice of incorporating 1 or more ESIs into the initial nonoperative management of patients with spinal stenosis, these results suggest that ESI is associated with worse outcomes.

The second study was a placebo-controlled trial to investigate the comparative effectiveness of either a single corticosteroid injection, multimodal physiotherapy, or both in 165 patients who experienced chronic, painful unilateral epicondylalgia (ie, “tennis elbow”) [Coombes et al. 2013]. Patients were randomized to 1 of 4 groups: A. corticosteroid injection (n = 43); B. placebo injection (n = 41); C. corticosteroid injection plus physiotherapy (n = 40); or, D. placebo injection plus physiotherapy (n = 41). Overall, subjects were 49 years old on average, 38% female, with a mean 4 months duration of epicondylalgia producing moderate pain at worst (62mm on 100mm visual analog scale).

The 2 primary outcomes were (a) 1-year global rating of change scores for complete recovery or much improvement, and (b) 1-year recurrence (defined as complete early recovery or much improvement at 4-8 weeks, but not persisting at later time points up to 52 weeks) analyzed on an intention-to-treat basis. Secondary outcomes included complete recovery or much improvement at 4 and 26 weeks. All subjects and investigators were blinded regarding the injection solution (steroid or placebo), but blinding as to whether patients received physiotherapy was not possible.

Writing in the Journal of the American Medical Association (JAMA), Brooke K. Coombes, PhD, of the University of Queensland, Australia, and colleagues report that, in the 163 patients available for final analysis, corticosteroid injection alone produced significantly lower complete recovery or much improvement at 1 year compared with placebo injection (83% vs 96%, respectively; P=0.01)) and much greater recurrence than with placebo (54% vs 12%; P<0.001). There were no significant differences between the physiotherapy and no physiotherapy groups at 1 year for complete recovery or much improvement (91% vs 88%, respectively) or for recurrence (29% vs 38%).

Similar patterns were found at 26 weeks. There was significantly less complete recovery or much improvement after corticosteroid injection versus placebo injection, and no differences between the physiotherapy and no physiotherapy groups.

In the short-term, at 4 weeks, the corticosteroid injection was superior to placebo in reducing pain and disability. And, there were greater improvements associated with physiotherapy compared with groups not receiving physiotherapy; however, there were no added benefits of combining the steroid injection with physiotherapy.

The researchers conclude that, in this placebo-controlled study of patients with lateral epicondylalgia, a single, blinded injection of corticosteroid medication was associated with substantial pain relief in the short-term, but poorer long-term outcomes and higher recurrence rates 1 year after receiving an injection. At the same time, 8 weeks of multimodal physiotherapy — comprising elbow mobilization with movement and exercise — did not optimize long-term outcomes, but was somewhat beneficial in the short-term in the absence of corticosteroid injection.

COMMENTARY: Taken together, the two studies above do not favor the use of corticosteroid injections for spinal stenosis or epicondylalgia. Previous Pain-Topics UPDATES during just this past year have described research on the use of steroid injections for musculoskeletal conditions — primarily epidural injections for neck and back pain — and the results were similarly unfavorable. For example, see the UPDATES articles [here], [here], [here], and [here].

Overall, epidural steroid injections for musculoskeletal pain are somewhat commonplace. The procedures are typically used to treat joint pain of various types, spinal stenosis, spondylolysis, herniated or degenerative discs, or sciatica and other spinal nerve entrapments. However, because the anti-inflammatory effects of the steroid agents, which are usually mixed with a local anesthetic, are relatively short-term, the injections provide only temporary relief of pain, if any, and repeat procedures with their potential risks are frequently necessary.

The findings of the first study described above — by Radcliff et al., in which epidural steroid injection (ESI) actually worsened long-term spinal stenosis outcomes with or without surgery — were unexpected by the researchers. As such, they caution that the results should be viewed cautiously, since there might have been unknown, confounding factors biasing the outcomes.

Among other possibilities, the researchers hypothesize a most likely explanation for the surprising outcome may be that the additional volume of the ESI and/or the steroid material itself might exacerbate the underlying central stenosis and radiculopathy, after the initial pain-relieving effects of the injection have dissipated. Thus, they note, “ESIs may temporarily diminish pain but may actually potentiate damage to the nerve roots in the long term, which ultimately diminishes clinical outcomes even after a successful decompression operation.”

Among the limitations of their study, Radcliff and colleagues suggest that the findings of increased operative time and blood loss were unexplained and therefore may be coincidental and unrelated to ESI itself. Also, their study outcome effects were based on a retrospective subgroup analysis of data from a much larger study, which was not designed in advance (a priori) to measure such effects.

Additionally, various techniques were used to administer the ESIs, and information was unavailable as to whether injections were fluoroscopically guided or regarding the nature of the corticosteroid solutions administered (eg, particulate vs nonparticulate). Finally, patients were not randomized to ESI versus no-ESI groups and, although the two groups were quite similar on all baseline measures, there is a possibility that unknown confounders might have biased the results.

The second study examining epicondylalgia, or “tennis elbow,” was complex in design — with 4 groups, multiple time points, and numerous outcome measures — and the published report was overladen with data that could be confusing and misinterpreted. Overall, recovery rates without recurrence were relatively high across all patients in all groups, including the placebo group, which may reflect the natural course of the condition. However, the addition of a corticosteroid injection incurred added cost, inconvenience, and some procedural risk and discomfort without any improvement in long-term benefits.

Physiotherapy alone, without added steroid injection, modestly increased the rate of recovery or much improvement and reduced the use of analgesic or anti-inflammatory medications. However, allowing subjects to use non-protocol medications, heat or cold packs, or braces — as was permitted throughout the study — may have been an uncontrolled, confounding factor.

Furthermore, the researchers advise that their results may not have external validity in other clinical contexts in which treatments are reserved for specific individuals or combined in a different sequence or manner: for example, injection of patients who have not recovered after a period of wait-and-see or physiotherapy, or treatment with physiotherapy in patients with poor late outcomes after injection.

Coombes et al. speculate that, in epicondylalgia, corticosteroids may not adequately ameliorate key features of the associated tendinopathy brought on by overuse and cumulative trauma. In fact, steroids may be histologically deleterious to the tendon and the short-term pain relief afforded by the injection may encourage excessive early activity and exacerbation of injury.

In sum, the research evidence to date for corticosteroid injections does not seem favorable overall regarding long-term benefits for pathologies of the spine or musculoskeletal conditions like epicondylalgia. Certainly, some patients may be helped, but results appear to be unpredicatable. Specific reasons for this are still unclear and further laboratory and prospective clinical research seems necessary for delineating the causes.

> Coombes BK, Bisset L, Brooks P, et al. Effect of Corticosteroid Injection, Physiotherapy, or Both on Clinical Outcomes in Patients With Unilateral Lateral Epicondylalgia: A Randomized Controlled Trial. JAMA. 2013;309(5):461-469 [abstract here]
> Radcliff K, Kepler C, Hilibrand Alan, et al. Epidural Steroid Injections Are Associated With Less Improvement in Patients With Lumbar Spinal Stenosis: A Subgroup Analysis of the Spine Patient Outcomes Research Trial. Spine. 2013;38(4):278-291 [
article here].

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