Background/Purpose: Osteoarthritis (OA) is the most common form of arthritis worldwide and is becoming more prevalent with the increasing age of the population.  As Intra-articular Corticosteroids (IACS) in clinical practice are often given serially to improve patient symptoms, we undertook this systemic review to summarise literature for the two key clinically relevant questions- are multiple IACS injections effective for OA and are they safe?

Methods: Systematic literature searches was performed in January 2019 using the databases MEDLINE, EMBASE, AMED, Web of Science, PubMed, Cochrane Library, and Google Scholar. Relevant references were also explored. A structured search strategy was used for both efficacy and safety. Data extracted included study design characteristics, participant details, characteristics of IACS (including dosage, frequency and duration of treatment), comparator used and outcomes examined. Any discrepancies were resolved through discussion of papers by the reviewers.

Results: Six RCTs were included for efficacy assessment (Table 1). The use of multiple IACS appeared to be better than comparator (SMD for pain -0.47, 95% CI -0.62, -0.31). An I² statistic of 92.6% indicates a great deal of heterogeneity (figure 1). However one study stood out strongly in favour of IACS (SMD -1.63, 95% CI -1.95, -1.31). With a weighting of 23% this was further excluded as an outlier of results. This resulted in the overall change in VAS between IACS and comparator being not statistically different (SMD -0.12, 95% CI -0.29, 0.06), with improved heterogeneity (I² 0.00%, p value 0.444).

Subgroup analysis by comparator showed no separation of regular IACS from placebo, though timing of pain assessments was questionable. Figure 2 shows the subgroup analysis according to varying time points at 6, 12, 26, 52 and 106 weeks. Apart from pain reduction on 26 months (SMD -0.55, 95%CI -1.06 to -0.05), no difference was observed between IACS and comparator.

Fourteen RCTs and two observational studies were assessed for the safety of multiple IACS. Minor local adverse events were similar in both groups. One RCT found that regular IACS every 3 months for 2 years caused greater cartilage loss compared to saline injection (-0.21mm vs 0.10mm). One cohort study found that multiple IACS injections associated with worsening of joint space narrowing (HR 3.02, 95% CI 2.25-4.05) and increased risk of total joint replacement (HR 2.54, 95% CI 1.81- 3.57).

Conclusion: This systematic review included RCTs of regularly repeated IACS injections, using different steroid regimes and different joint sites, and with infrequent pain assessment predominantly undertaken just prior to each injection. This makes it difficult to come to any firm conclusion about the efficacy of multiple IACS injection however it would appear that multiple IACS injections overall are no better than placebo for OA pain. The preliminary finding of a detrimental effect on structural OA progression warrants further investigation. Efficacy and safety of multiple IACS reflecting recommended best practice has yet to be assessed.

TMJ temporomandibular joint; CMC carpometacarpal joint

Figure 1- Forest plot of effects size for pain relief

Figure 2- Forest plot of subgroup analysis of pain scores according to varying time points

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-multiple-intra-articular-corticosteroid-injections-for-osteoarthritis-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials-and-observational-studies/