Cortico-Steroid Injections – the End Is Coming…

Blog post produced and written by Clinic Manager and Sports Injury Specialist Jason Dodd.

I recently wrote an article (which can be found here) on my reasons against cortico-steroid injections. Whilst it has been a popular feature for many years within clinical settings, little is discussed about the risks surrounding this intervention. It seems quite a good time to be able to talk again about this with the latest news on the Covid-19 vaccine that is imminent. Whatever your thoughts are on this vaccine, we are all in agreement that taking this vaccine comes with inherent risk (proven or not proven) as we are unable to determine the long term side effects (we cannot fast forward into the future unfortunately) so we do not know what will happen in the next 10 years. This is a decision that needs to be weighed up as to whether you have the vaccine or not.

However, what we do have evidence of is a much talked about and often sought after treatment known as steroid injections. These injections are known as the answer to reduce pain in the affected area and allow you to go about your daily lives as normal. What is not known is that these injections are given with the aim of enabling the patient to start a rehabilitation programme and are not the sole answer in isolation.

Over the years though, more and more research is evolving which is now showing the true side effects of these injections. Once though quick fix and solution is now proving to be a quick route to degenerative joints and actual increases in joint pain (and at best offering no improvement in long term pain). This information below is a summary of a wide range of research trials conducted within the last 3 years which show the outcomes of these injections and the effects they may have. Obviously the content here is purely for educational purposes and I am not trying to dictate your decision. Ultimately that rests with you, I just want to ensure you have all the FACTUAL information required before making your decision. Below is a selection of studies which show the results of various trials conducted with their outcome and the conclusion that is drawn.

Study 1

Davis 2019 Nested cohort study of 1935 patients

Focus, Patients at risk of but without radiographic knee OA followed for 8 years to assess development of either knee OA or accelerated knee OA

Key Findings, Patients who underwent any procedure (injection or knee arthroscopy) or took pharmaceuticals were all more likely to develop accelerated knee OA. The relationship was particularly strong for knee arthroscopy and IAC (P<0.001)

Limitations (JO), Non-randomised study, and clearly confounding factors not accounted for may have increased risk of both knee OA and likelihood of undertaking treatment

Conclusions, Both IAC and knee arthroscopy are associated with (but did not necessarily cause) an increased risk of accelerated knee OA occurring in patients without radiographic OA

Study 2

Deyle 2020 RCT in NEJM of 156 patients comparing physical therapy and IAC injections

Focus, Single-blinded RCT comparison between IAC and physical therapy for knee OA patients

Key Findings, Physical therapy patients had significantly greater improvement at 1 year follow-up than IAC patients

Limitations (JO), The physical therapy intervention was "mixed" (combination of hands-on treatment and exercise-based). There was no placebo control group.

Conclusions, This trial could be interpreted as being either supportive of combination physical therapy or, alternatively, a warning that IAC may not yield as good a result as a comparator treatment

Study 3

Mackowiak 2020 Retrospective cohort study of 126,000 insurance claim patients

Focus, Comparison of ongoing costs between knee OA patients who were treated with (only) IAC or knee arthroplasty or hyaluronan injections

Key Findings, Hyaluronan injection patients had significantly fewer costs, requirements for ongoing painkillers or adverse events over 4 years than either IAC or knee arthroplasty patients. Compared to knee arthroplasty patients, IAC patients had fewer adverse events and medical costs in the first year of follow-up, but more adverse events and use of painkillers in years 2-4.

Limitations (JO), Non-randomised. Funded by a company which manufactures a hyaluronan injection, which may have biased the study

Conclusions, Although this was promoted by the authors as a cohort study supportive of hyaluronan injections, it equally could be read as a warning against the short-term harms of knee arthroplasty and the longer-term harms of IAC

Study 4

Wijn 2020 Cohort study of 4796 patients

Focus, Patients with or at risk of knee OA followed for 9 years, comparing risk of requiring knee arthroplasty for those who used IAC to those who did not

Key Findings, Each IAC injection increased the absolute risk of arthroplasty by 9.4% at nine years' follow-up compared with those who did not receive injections

Limitations (JO), Non-randomized study, with the possibility that those patients more willing to undertake injections were more willing to undertake arthroplasty

Conclusions, Possible that IAC leads to an increase in risk of long-term worsening of knee OA, resulting in higher rates of knee arthroplasty

Study 5

McAlindon 2017 Randomized controlled trial

Focus, Medium-term (3 months to 2 years) efficacy and safety (140 patients)

Key Findings, Intra-articular triamcinolone injection every 3 months resulted in greater cartilage volume loss detected on MRI at 2 years than did saline for a mean change in index compartment cartilage thickness of -0.21 mm vs -0.10 mm (between group difference -0.11mm, 95% CI -0.20 to -0.03mm). There was no clinically important difference in pain (-1.2 vs -1.9, between group difference 0.6, 95% CI -1.6 to 0.3).

Limitations (JO), Measurements were only made 3 months after each injection and could possibly have missed short-term improvements of IAC over placebo.

Conclusions, IAC provided no benefit over placebo in time frames from 3 months to 2 years, but was associated with progressive cartilage deterioration

Study 6

Liu 2018 Cohort study (412 patients)

Focus, Long-term effectiveness (2 years) as assessed by symptoms compared to controls

Key Findings, Compared to non-users participants initiating CSI experienced worsening of pain (yearly worsening: 1.24 points, 95% CI 0.82-1.66 on the WOMAC 20 point scale), along with worsening of stiffness and physical functioning after adjusting for potential confounders.

Limitations (JO), Cohort design rather than RCT is less powerful at eliminating confounders

Conclusions, IAC was associated with worsening symptoms over 2 years follow up

Study 7

Zeng 2019 Cohort study (148 IACs initiators, 536 comparators)

Focus, Radiographic progression of knee osteoarthritis with IAC compared to controls (propensity-score matched)

Key Findings, Compared to non-users, hazard ratios (HRs) of joint structure worsening over 48 months from IAC initiation and continuous IACs were 3.02 (95% CI, 2.19-4.16) and 4.67 (95% CI, 2.92-7.47), respectively.

Limitations (JO), Cohort design rather than RCT is less powerful at eliminating confounders

Conclusions, CSI was associated with increased risk of structural deterioration and progression to knee replacement

Study 8

Kompel 2019 Case series of 459 patients

Focus, Rate of rapid progression of hip and knee OA cases after guided IAC

Key Findings, 8% of knee OA cases exhibited rapid deterioration within 2 years of IAC

Limitations (JO), No control group

Conclusions, Study has several limitations but warrants further investigation

Study 9

Pelletier 2020 Case-control study

Focus, Structural changes on MRI scan after IAC

Key Findings, No change in articular cartilage thickness but a change in meniscal thickness

Limitations (JO), Case-control methodology not ideal for assessing structural deterioration

Conclusions, Shows a single change (reduction in meniscal thickness) but which is in keeping with others that flag deterioration of joint integrity after IAC

Study 10

Elksniņš-Finogejevs 2020 RCT between PRP and IAC

Focus, RCT comparing Platelet Rich Plasma (PRP) injection with cortisone injection >12 month follow up.

Key Findings, PRP had superior VAS, KSS and IKDC scores at 15, 30 and 58 weeks to cortisone. In addition 3/20 IAC patients elected to have knee replacement within the year (0/20 for PRP)

Limitations (JO), Non blinded study and no placebo group. Small sample size albeit statistical significance reached showing large difference between the groups

Conclusions, Doesn't differentiate between possibility that PRP is placebo and IAC is harmful relative to placebo, or that both groups may be beneficial, with PRP being of greater benefit to IAC.

Study 11

Gregori 2018 Systematic review of all pharmacological interventions for knee OA (33 interventions, 47 RCTs, 22037 patients)

Focus, Long term pain control (>12 months)

Key Findings, Intermittent IAC injections were not associated with pain improvement in the long term. Combination with hyaluronic acid injection had moderately beneficial but variable effect on pain.

Limitations (JO), Very few studies examine medium to long-term effect of IACs alone

Conclusions, Based on limited evidence, IAC was not associated with pain improvement beyond 12 months

Overall Conclusion

1. Multiple long-term studies assessing IAC for knee OA from 2017-2020, some RCT and many cohorts adjusted for confounding.
2. There is no benefit for IAC for knee OA in the longer term, but it is associated with cartilage degeneration, worsening clinical outcomes and a higher risk of progressing to knee replacement
3. There is not (yet) a smoking gun 5-10 year follow-up RCT showing all of these negative associations in a single study.
4. With no long-term benefit and now a large number of studies showing worse outcomes than placebo and other comparators, IAC cannot be recommended as a treatment for knee OA.

References

1. Orchard JW. Is there a place for intra-articular corticosteroid injections in the treatment of knee osteoarthritis? Bmj 2020;368:l6923.
2. Jüni P, Hari R, Rutjes A, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev 2015:Oct 22;(10):CD005328.
3. Gregori D, Giacovelli G, Minto C, et al. Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. Jama 2018;320(24):2564-79.
4. Davis JE, Harkey MS, Liu SH, et al. Adults With Incident Accelerated Knee Osteoarthritis Are More Likely to Use Pharmacological Treatment Options and Receive Arthroscopic Knee Surgery: Data From the Osteoarthritis Initiative. ACR open rheumatology 2019;1(6):359-64.
5. Deyle GD, Allen CS, Allison SC, et al. Physical Therapy versus Glucocorticoid Injection for Osteoarthritis of the Knee. N Engl J Med 2020;382(15):1420-29.
6. Mackowiak J, Jones JT, Dasa V. A comparison of 4-year total medical care costs, adverse outcomes, and opioid/prescription analgesic use for 3 knee osteoarthritis pain treatments: Intra-articular hyaluronic acid, intra-articular corticosteroids, and knee arthroplasty. Semin Arthritis Rheum 2020.
7. Wijn SRW, Rovers MM, van Tienen TG, et al. Intra-articular corticosteroid injections increase the risk of requiring knee arthroplasty. The bone & joint journal 2020;102-b(5):586-92.
8. McAlindon TE, LaValley MP, Harvey WF, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. Jama 2017;317(19):1967-75.
9. Liu SH, Dubé CE, Eaton CB, et al. Longterm Effectiveness of Intraarticular Injections on Patient-reported Symptoms in Knee Osteoarthritis. J Rheumatol 2018;45(9):1316-24.
10. Zeng C, Lane NE, Hunter DJ, et al. Intra-articular corticosteroids and the risk of knee osteoarthritis progression: results from the Osteoarthritis Initiative. Osteoarthritis Cartilage 2019.
11. Kompel AJ, Roemer FW, Murakami AM, et al. Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought? Radiology 2019:190341.
12. Pelletier JP, Raynauld JP, Abram F, et al. Intra-articular corticosteroid knee injection induces a reduction in meniscal thickness with no treatment effect on cartilage volume: a case-control study. Sci Rep 2020;10(1):13789.
13. Elksniņš-Finogejevs A, Vidal L, Peredistijs A. Intra-articular platelet-rich plasma vs corticosteroids in the treatment of moderate knee osteoarthritis: a single-center prospective randomized controlled study with a 1-year follow up. Journal of orthopaedic surgery and research 2020;15(1):257.