Authors' objectives: Intra-articular glucocorticoid injection (IAGI) is utilised and publicly reimbursed in Switzerland for patients with knee or hip osteoarthritis (OA). However, systematic reviews on the efficacy and safety of IAGI indicate limited or unclear benefits compared to placebo or no treatment. This health technology assessment (HTA) investigates the safety, efficacy, cost-effectiveness, budget impact and other issues related to IAGI in patients with hip or knee OA compared to sham, placebo or no treatment.

Authors' results and conclusions: Clinical evaluation Sixteen RCTs comprising 1,522 patients were evaluated for knee OA, and 4 RCTs with a total of 239 patients were included for hip OA. For knee OA, the evidence suggests that IAGI results in little to no difference in pain at 3 months (SMD -0.04, 95% CI: -0.29 to 0.21, low certainty evidence); however, there may be a small reduction in pain in patients receiving IAGI at 1 month (SMD -0.30, 95% CI: -0.52 to -0.08, with substantial heterogeneity, I 2 = 65.25). IAGI may result in little to no difference in function (MD 0.00, 95% CI: -1.08 to 1.09, low certainty evidence), and likely results in little to no difference in HRQoL (MD 1.80, 95% CI: -2.88 to 6.48, moderate certainty evidence) at 3 months, or at any other timepoints. The evidence suggests IAGI probably results in little to no difference in care utilisation at 3 months (MD -0.19, 95% CI -0.59 to 0.21, moderate certainty of evidence); however, IAGI likely reduces care utilisation up to 1 month (MD -0.43, 95% CI -0.81 to -0.05). There is probably no difference in the rate of AEs (moderate certainty evidence), and a high degree of uncertainty in the rate of SAEs (low certainty evidence) for IAGI compared to sham. No studies reported joint replacement surgery or treatment satisfaction. For hip OA, there is no evidence of a difference between IAGI and sham injection in relation to pain at 3 months (SMD -0.28, 95% CI: -0.76 to 0.20, very low certainty evidence), but the evidence is very uncertain; there is a large difference favouring IAGI at 1 month (SMD -1.60, 95% CI -2.70 to -0.51). No other timepoints were reported. Regarding function, 3-month data were not reported. IAGI may improve function at 1 month (SMD -1.74, 95% CI: -3.08 to -0.41, very low certainty evidence), but the evidence is very uncertain. Data at other timepoints were not reported. Regarding HRQoL, 3-month data were not reported. Evidence suggests HRQoL may be improved with IAGI at 1 month (MD 5.29, 95% CI: -0.10 to 10.68, very low certainty evidence). Data at other timepoints were not reported. There was no evidence of a difference for care utilisation (very low certainty evidence), AEs (very low certainty evidence) and SAEs (very low certainty evidence), noting that the incidence of AEs and SAEs was low in both groups. No studies reported joint replacement surgery or treatment satisfaction. Economic evaluation Only one cost-effectiveness study meeting the PICO criteria (population, intervention, comparator, outcome) for knee OA was identified. This study, from the New Zealand healthcare payer perspective, assessed the cost-utility of IAGI as an adjunct to core treatment compared to core treatment alone, finding IAGI to be a cost-effective adjunctive therapy. Despite differences in the modelling methodologies between the current HTA and the New Zealand study, the overall findings appear to be in broad alignment, with incremental cost-effectiveness ratios (ICER) of NZD24,532 (CHF17,774) and CHF12,456 per QALY gained, respectively. In probabilistic analysis, 22.0% of iterations fell in the fourth quadrant of the cost-effectiveness plane, where IAGI is dominated (i.e. is more expensive and less effective than standard care). Mean expected incremental QALYs gained was estimated at 0.013 (95% CI: -0.019 to 0.044). Results from the current HTA suggest IAGI has 71.9% and 75.0% probability of being cost-effective at hypothetical willingness-to-pay thresholds of CHF50,000 and CHF100,000 per QALY gained, respectively. The net financial impact of IAGI for knee OA under current policy conditions was estimated at CHF0.82 million in 2025, increasing to CHF0.97 million in 2029. For hip OA, the net financial impact was estimated at CHF0.52 million in 2025, increasing to CHF0.57 million in 2029. Ethical, legal, social and organisational evaluation Thirteen publications relating to ethical and social issues were identified; none were identified relating to legal or organisational considerations. Regarding ethical issues, informed consent was emphasised. Social issues identified that patient education highlighting the benefits of exercise and weight loss for treating hip and knee OA was an important factor in empowering individuals to maintain social activities. Survey findings indicate that individuals who derived benefits from exercise also generated positive beliefs and motivated others to persist in exercise routines. Knowledge about the importance of exercise and weight loss in managing OA served as a significant facilitator. Conversely, the belief that exercise could worsen the condition hindered physical activity, especially when individuals perceived OA as an inevitable ‘wear and tear’ issue. Conclusions Overall, neither of the populations reported improvements in pain, function or HRQoL at 3 months or beyond; however, both groups reported improvements in pain favouring IAGI at 1 month, and HRQoL may be improved in hip patients at 1 month. Patients with knee OA also experienced a decrease in care utilisation at 1 month; however, patients with hip OA may not experience a change in care utilisation. There were no significant safety concerns associated with IAGI in patients with either knee or hip OA at the longest follow-up. Other outcomes were not reported. Economic modelling explored the cost utility of a single IAGI in the management of knee OA as an exemplar case. The estimated base case ICER (CHF12,456 per QALY gained) broadly aligned with the results from the available published literature. However, probabilistic analysis performed for the present evaluation highlighted uncertainty in the treatment benefit attributed to IAGI, contrasting with the existing study, which indicated confidence that IAGI was associated with a positive treatment effect. There is also uncertainty in the applicability of the estimated benefit to the Swiss population.

Authors' methods: The clinical evaluation included a systematic review of randomised controlled trials (RCTs) by searching Embase, Medline and the Cochrane Library up to 4 October 2023. Outcomes of interest included function, pain, health-related quality of life (HRQoL), joint replacement surgery, care utilisation, treatment satisfaction, adverse events (AE) and serious adverse events (SAE). Longitudinal meta-analyses (LMA) were conducted where possible; otherwise, separate pairwise meta-analyses were conducted at individual timepoints. Continuous outcomes were reported as standardised mean differences (SMD) or mean differences (MD), and dichotomous outcomes were reported as risk ratios (RR), all with corresponding 95% confidence intervals (CI). For SMDs, a difference of 0.2 was considered to be a small effect, 0.5 moderate and 0.8 large. For efficacy outcomes, treatment effects were evaluated at 3 months (primary endpoint), as well as at 1, 6 and 12 months (secondary endpoints); safety outcomes were reported at longest follow-up. While the 3-month data provide information in line with the treatment goals of IAGI, it is worth highlighting that other timepoints also provide information on the durability of the treatment effect and should not be considered as less clinically relevant than the primary endpoint. Heterogeneity was evaluated qualitatively (forest plots) and quantitatively (I², ꭕ², ͳ²). Risk of bias (RoB) was assessed using Cochrane RoB 2.0, and the overall strength of evidence for important outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach at the primary endpoint. The economic evaluation included a systematic review of economic studies, which was undertaken in the same databases plus Econlit and the International Network of Agencies for Health Technology Assessment (INAHTA) database. The websites of HTA institutes and database searches were conducted up to 16 October 2023. Modelling was undertaken to explore the cost-utility of a single IAGI in the management of knee OA as an exemplar case. The analysis examined IAGI as an adjunct to standard care compared to standard care alone. To derive quality-adjusted life year (QALY) estimates, reported outcomes were mapped into a preference-based utility measure. Expected per patient costs for the delivery of a single injection were estimated for both knee and hip OA. Current utilisation of IAGI among Swiss patients diagnosed with primary OA of the knee or hip was estimated and extrapolated to predict the future budget impact of IAGI to the Swiss healthcare payer. No limitation or disinvestment scenario modelling was undertaken.

Project Status: Completed

URL for project: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-projekte/glucocorticosteroide.html

URL for protocol: https://www.bag.admin.ch/dam/bag/en/dokumente/kuv-leistungen/leistungen-und-tarife/hta/berichte/h0058csoa-hta-protocol.pdf.download.pdf/h0058csoa-hta-protocol.pdf

Year Published: 2024

URL for published report: https://www.bag.admin.ch/dam/bag/en/dokumente/kuv-leistungen/leistungen-und-tarife/hta/berichte/h0058csoa-hta-report.pdf.download.pdf/h0058csoa-hta-report.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Switzerland

Organisation Name: Swiss Federal Office of Public Health (FOPH)

Contact Address: Federal Office of Public Health, Schwarzenburgstrasse 157, CH-3003 Berne, Switzerland

Contact Name: Stephanie Vollenweider

Contact Email: hta@bag.admin.ch

Copyright: Swiss Federal Office of Public Health