Steroid knee injections: do they help??

A recent article in JAMA found that regular injections of intra-articular steroids was associated with decreased knee cartilage volume and no real improvement in pain in patients with knee osteoarthritis (see knee pain steroids not help JAMA2017 in dropbox, or doi:10.1001/jama.2017.5283).

​Details:

--140 patients with symptomatic knee osteoarthritis as well as synovitis by ultrasound (evidence of effusion synovitis, with suprapatellar pouch depth >2mm) were randomized to receiving intra-articular 1cc triamcinolone 40mg vs 1cc saline every 3 months for 2 years, both without local anesthetic

--mean age 58, 54% women, BMI 31, 65% white, mean hemoglobin A1c=6%, CRP 0.5

--all patients had radiographic evidence of Kellgren-Lawrence knee OA grade 2 or 3 (grade 2= definite osteophytes and possible joint space narrowing on anteroposterior weight-bearing radiograph; grade 3= multiple osteophytes, definite joint space narrowing, sclerosis, possible bony deformity)

--knee MRI was done at baseline and then annually

Results:

--there was greater cartilage loss with injected steroids (volume loss of 0.21 mm vs 0.10 mm with normal saline), though the amount of superficial fibrillations (fraying of the articular surface) was more common in the saline group (34% vs 13%)

--no significant difference between the groups in pain scores, or functional activities such as the 20 meter-walk time or the chair-to-stand time (these were all measured after asking patient to not take pain meds for 2 days prior to their evaluations)

--adverse events: overall more significant in saline group (63 vs 52, p=0.02), though no difference in what was considered treatment-related.  Cellulitis in one patient in the saline group, also hemoglobin A1c actually decreased significantly in the steroid group (-0.1% vs increase of 0.2% in the saline group, and this was controlling for BMI, radiographic DJD classification, sex). No difference in hypertension

Commentary:

--As noted in a recent blog on the lack of benefit of arthroscopy in patients with degenerative knee disease (see http://gmodestmedblogs.blogspot.com/2017/05/against-arthroscopy-for-djd-of-knees.html  ), knee DJD is remarkably common and a leading cause of  disability (and medical costs, largely for procedures)

--the physiologic rationale for intra-articular steroid injections is that DJD is typically associated with synovitis, with its associated elaboration of biochemical mediators having the potential for causing further joint destruction (collagenases, aggrecanases, cytokines). And local steroids might decrease the inflammation and this destructive cycle. Animal studies have supported this hypothesis. This study, utilizing MRI to assess the steroid effects on cartilage, seems better designed than prior studies which have used xrays, given how insensitive xrays are to assessing the radiolucent cartilage.

--so, how can one reconcile the conclusions of this study (negative impact on cartilage and no effect on pain) with the other studies finding pain improvement in the 4 weeks after the injection, an older but smaller study of 68 patients with the same basic protocol as in this study finding some benefit for pain, and with the huge anecdotal experience of benefit (steroid injections are done increasingly commonly)???

    --these patients had pretty mild DJD, especially in terms of baseline symptoms, with a WOMAC pain score of 8.3. This score is based on 5 items (pain during walking, using stairs, in bed, sitting or lying, and standing upright, each with a score of 0-4, ranging from  None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4); ie total maximum score of 20, with an average score of 8, as in the above study, being between mild and moderate.

    --one issue with knee OA is how to define it or its progression objectively. The Framingham Study found a poor correlation between radiographic knee OA and symptoms (see Hannah MT. J Rheumatol 2000; 27: 1513, for example). And there is no accepted minimal clinically important difference for MRI cartilage measurement, as duly noted by the authors of this study. Also, I am concerned about the increase found in cartilage fibrillation found in the non-steroid group, since this early splitting of the tangential cartilage surface might harken more severe and clinically important cartilage changes over the somewhat longer term

    --they only assessed pain relief at the 3-monthly evaluation, with no data on how patients fared in the first 1 or 2 months [and, in my pretty extensive experience with knee injections, probably around 1000 over the years, the vast majority of patients getting relief for the first few months, some much longer, and that relief translates into dramatic improvement in function and pain relief; ie they can walk and actually do things they couldn’t do before]

    --there are even some literature (a meta-analysis of 38 studies) supporting saline injections as  helping with pain relief [ie, their control injections were not necessarily sham injections; saline itself may have some benefit. Which is an important difference. There seems to be a more profound placebo effect with injections than pills, so perhaps the real control for this injection study should be a needle in the joint with no meds injected???]

    --and, in terms of generalizability of these results, it is important to stress that these patients had clinically mild knee OA at baseline, but still received injections every 3 months [not necessarily common clinical practice for those with mild-to-moderate symptoms], so their results might not apply to many patients who are actually getting knee injections for more severe, functionally limiting pain despite exercise/physical therapy/etc

    --what about the decrease in cartilage thickness?? This is certainly concerning, though perhaps there are non-measured countervailing processes going on: are patients getting a lot of early pain relief [a good thing], but then using their knees more [walking, etc] which leads to more cartilage destruction through wear-and-tear???  And, though small, does the relative improvement in A1c in the steroid group reflect the patients’ ability to do more exercise?

So, how should this study affect clinical practice??

    --my non-rigorously-tested finding, through loads of knee injections, is that 90+% of patients have much less pain and are able to function much better after injections, and I will continue to do injections

    --that being said, injections should be accompanied with aggressive patient education around the importance of quadriceps strengthening exercises, which often help a lot [there were older studies suggesting this may not be true in patients with misaligned knees, perhaps from more severe DJD, where the patella does not track correctly and quad strengthening might exacerbate knee symptoms, but my sense is that this is relatively uncommon].  And some patients need a knee injection in order to do more exercise or physical therapy…

    --other therapeutic options are sparse. Arthroscopic meniscal repair or joint lavage seems to do nothing (per recent blog mentioned above). Physical therapy is important, but does not help many patients much (especially those who are frail, have advanced DJD, are unable to do the necessary home-based exercises,…). NSAIDs have a wide array of undesirable adverse effects, especially in the population with symptomatic knee OA, since they are typically older and have lots of comorbidities (and in this study, unlike NSAIDs, steroids were not associated with hypertension, for example)

    --I also use the equivalent of 40 mg triamcinolone with 2cc of 1% lidocaine. This might have better efficacy (unknown to me) than just 1 cc of triamcinolone alone, since the added volume of the anesthetic may help the steroid reach more areas of the inflamed knee joint, and perhaps the anesthetic improves the pain relief beyond the steroid itself.

    --after I have done a few knee injections, especially if there are diminishing returns (the first injections working for much longer than subsequent ones), I do discuss and recommend consideration of surgical management (usually knee replacement surgery)

    --but I am certain that I will continue having patients, especially older ones, who often have serious medical comorbidities, who adamantly refuse surgery and really want repeated knee injections (even every 2-3 months) in order to function.  This study will change my practice in that I will discuss the issue of potential cartilage harm more forcefully than previously.

    --one important general issue is my concern about the quick summaries of potentially clinically very important articles:  the one-line synthesis of this study was “Intra-Articular Corticosteroids Show No Benefit in Knee Osteoarthritis”in Physician’s First Watch/NEJM Journal Watch, and there was little more added in the few summary lines. I am very concerned that this type of analysis may undercut an important therapeutic modality for many patients, perhaps leading to fewer injections even though the patient may achieve very important pain relief and improved functioning/quality of life.  This brings up one of the reasons I do these blogs: we in primary care clinical practice are inundated with new articles (mostly drug-company sponsored) and new guidelines (often done by specialty societies whose members directly or indirectly are involved with drug companies, etc) on a daily basis. It is essentially impossible to keep up with the information onslaught. The summary services such as Journal Watch are really helpful in scanning the literature and alerting us to new articles/guidelines that might affect our clinical practice. But they may well have the very negative effect of dumbing down the literature to quick quips (sound bites?) that really make it impossible to figure out if a certain article or guideline really should apply to the patient sitting in front of us. My hope with these blogs is to look at a few of these articles that might well affect practice, give sufficient (and accurate) summaries of the methodology, types of patients involved, procedures done, and their results; then briefly put in my sense of how this article fits in with older literature and our model of disease physiology; and provide some specific concerns, if any, which might affect its clinical utility. This way, the reader can decide what they think about the article (or guideline), be able to review the specifics of the study​, even use my link to see the study itself for more details, and then figure out how or if they will integrate it into their practice