This article filled with reproach for non-steroidal anti-inflammatories was highlighted in a New England Journal of Medicine Journal Watch and on Twitter – a wistful treatise remarking on the general ineffectiveness of pharmacologic analgesics. “Nothing works!” accompanied by a general gnashing of teeth and writhing on invisible flames.
But – does this meta-analysis actually reach such a conclusion? Examine the first few words in their conclusion:
NSAIDs are effective for spinal pain …
Off to a good start! But, the catch:
… but the magnitude of the difference in outcomes between the intervention and placebo groups is not clinically important.
These authors pool the results of 35 randomized, placebo-controlled trials for “spinal pain”, which is to say undifferentiated pain relating anatomically to any part of the spine. These trials comprised 6,065 participants – or, if you do the math, an average of 173 patients per trial, nearly all of them performed over a decade ago. The pooled effects of these trials all favored NSAIDs – but, as the authors mention, the absolute magnitude of effect on pain scales was a the edge of their threshold for clinical significance. The authors defined a difference of 10 points on a 100-point scale as clinically important, but most of their pooled results landed between -7 and -16, favoring NSAIDs over placebo. With these small samples, generally moderate GRADE quality, and moderate to high heterogeneity between the pooled results, there is a lot of fuzziness around their ultimate conclusion.
These authors do many, other, exploratory analyses, and it is reasonable to suggest the limitations inherent to each render any conclusions unreliable. Adverse events, as reported, were similar between groups – excepting for increased gastrointestinal adverse events, most of which were non-serious. The authors report this difference as a relative risk of 2.5 for GI side effects in their comparison, but the absolute differences are on the order of an excess of 1 in 100.
This is probably much ado about nothing. Their perspective is not inaccurate, per se, but these trials do find a consistent benefit to NSAIDs. The value judgment here on clinical effectiveness probably misses the mark, particularly considering these are inexpensive, readily available, with few adverse effects in short-term use. I would probably argue it is easier to defend a position they still have utility in multi-modal pain control regimens, rather than to conclude they be consigned to the rubbish bin.
“Non-steroidal anti-inflammatory drugs for spinal pain: a systematic review and meta-analysis”