Long-term use of corticosteroid injections for tendinopathy may be harmful, according to the results of a systematic review of randomized controlled trials reported in the October 22 issue of The Lancet.

“Few evidence-based treatment guidelines for tendinopathy exist,” write Brooke K. Coombes, MPhty, from the University of Queensland in St. Lucia, Queensland, Australia, and colleagues. “We undertook a systematic review of randomised trials to establish clinical efficacy and risk of adverse events for treatment by injection.”

The investigators searched 8 databases, without language, publication, or date restrictions, for randomized trials comparing the effectiveness of 1 or more peritendinous injections vs placebo or vs nonsurgical interventions for tendinopathy. Participants in these trials had to score 50% or more on the modified physiotherapy evidence database scale.

Relative risk and standardized mean differences (SMDs) were estimated from meta-analyses with use of a random-effects model. The main efficacy endpoints were pain score, as defined by protocol, in the short term (4 weeks; range, 0 – 12 weeks), intermediate term (26 weeks; range, 13 – 26 weeks), or long term (52 weeks; range, ≥ 52 weeks). Adverse events were also reported.

Of 3824 relevant trials identified, 41 met selection criteria, enrolling a total of 2672 participants. Many high-quality, randomized controlled trials had consistent results showing that corticosteroid injections were associated with pain relief in the short term vs other interventions, but this effect was reversed at the intermediate term and the long term.

Compared with no intervention, corticosteroid injection for lateral epicondylalgia had a large effect (defined as SMD > 0.8) on pain relief in the short term (SMD, 1.44; 95% confidence interval [CI], 1.17 – 1.71; P < .0001) in pooled analysis of treatment. However, corticosteroid injections were not significantly better than other interventions at the intermediate term (SMD, –0.40; 95% CI, –0.67 to –0.14; P < .003) or long term (SMD, –0·31; 95% CI, –0·61 to –0.01; P = .05).

For rotator cuff tendinopathy, the short-term efficacy of corticosteroid injections was also unclear. In trials that reported adverse events, only 1 (0.1%) of 991 participants who received corticosteroid injections had a serious adverse event (tendon rupture).

Compared with placebo, injections of sodium hyaluronate for treatment of lateral epicondylalgia were associated with pain reductions in the short term (SMD, 3.91; 95% CI, 3.54 – 4.28; P < .0001), intermediate term (SMD, 2.89; 95% CI, 2.58 – 3.20; P < .0001), and long term (SMD, 3.91; 95% CI, 3.55 – 4.28; P < .0001). Similar pain reductions were seen with botulinum toxin (short term; SMD, 1.23; 95% CI, 0.67 – 1.78; P < .0001), and prolotherapy (intermediate term; SMD, 2.62; 1·36 – 3·88; P < .0001).

However, lauromacrogol (polidocanol), aprotinin, and platelet-rich plasma were not more effective for Achilles tendinopathy pain reduction vs placebo, and prolotherapy was not more effective vs eccentric exercise.

“Despite the effectiveness of corticosteroid injections in the short term, non-corticosteroid injections might be of benefit for long-term treatment of lateral epicondylalgia,” the study authors write. “However, response to injection should not be generalised because of variation in effect between sites of tendinopathy.”

There was moderate evidence of harmful effects of repeated corticosteroid injection on pain, but the optimal number of doses and interval between injections are not known.

“We urge patients and practitioners to consider results of corticosteroid treatment that might not be defined as adverse, including negative long-term outcomes and high recurrence rates,” the study authors note .

Limitations of Review

Limitations of this systematic review include meta-analysis possible only for a few trials with sufficient homogeneity, and the possibility that useful clinical information could have been excluded.

“To address these limitations, future studies should address methodological features such as concealed allocation, intention-to-treat, and treatment masking,” the study authors conclude. “Additionally, recruitment of large sample sizes, standardisation of co-interventions, long-term follow-up, and systematic reporting of recurrence and adverse events are needed.”

Comment: Injections Not a Panacea

In an accompanying comment, Alexander Scott and Karim M. Khan, from the University of British Columbia in Vancouver, Canada, note that corticosteroid injections do provide short-term pain relief with low risk for tendon rupture or other adverse events.

“Today’s comprehensive meta-analysis highlights that patients who agree to receive other injection treatments, such as plasma-rich protein, prolotherapy, or sodium hyaluronate injections, should do so in the spirit of research volunteerism,” Drs. Scott and Khan write. “The meta-analysis could not find good-quality trials of these alternative therapies. Participation in clinical trials is laudable, and additional data will eventually clarify best practice; however, as yet there is no compelling evidence that any injection for tendinopathy is a magic bullet.”

“Non-steroidal anti-inflammatory drugs have neither randomised trial evidence, expert opinion support, nor a plausible mechanism to promote tendon healing and might inhibit tendon healing,” Drs. Scott and Khan conclude. “The evidence for specific exercise therapy is more encouraging than the evidence for corticosteroid injection, and exercise therapy is likely to promote protein synthesis via cell signalling. Specific exercise therapy might produce more cures at 6 and 12 months than one or more corticosteroid injections, and such was the case in today’s analysis.”

The National Health and Medical Research Council of Australia supported this study. The study authors and editorialists have disclosed no relevant financial relationships.

Lancet. Published online October 22, 2010.

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