Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study

Steven J Russell, Robert Sala, Philip G Conaghan, George Habib, Quang Vo, Rickey Manning, Alan Kivitz, Yvonne Davis, Joelle Lufkin, James R Johnson, Scott Kelley, Neil Bodick, Steven J Russell, Robert Sala, Philip G Conaghan, George Habib, Quang Vo, Rickey Manning, Alan Kivitz, Yvonne Davis, Joelle Lufkin, James R Johnson, Scott Kelley, Neil Bodick

Abstract

Objective: Approximately 30% of patients with type 2 diabetes mellitus have knee osteoarthritis. IA corticosteroids used to manage osteoarthritis pain can elevate blood glucose in these patients. We compared blood glucose levels following intra-articular injection of triamcinolone acetonide extended-release (TA-ER), an extended-release, microsphere-based triamcinolone acetonide formulation, vs standard triamcinolone acetonide crystalline suspension (TAcs) in patients with knee osteoarthritis and comorbid type 2 diabetes.

Methods: In this double-blind, randomized, parallel-group, phase 2 study (NCT02762370), 33 patients with knee osteoarthritis (American College of Rheumatology criteria) and type 2 diabetes mellitus (HbA1c 6.5-9.0% [48-75 mmol/mol]; 1-2 oral hypoglycaemic agents) were treated with intra-articular TA-ER (32 mg n = 18) or TAcs 40 mg (n = 15). Continuous glucose monitoring-measured glucose (CGMG) was assessed from 1 week pre-injection through 2 weeks postinjection. Endpoints included change in average daily CGMG from baseline (days -3 to -1) to days 1-3 postinjection (CGMGdays1-3) (primary) and percent time average hourly CGMG levels remained in prespecified glycaemic ranges.

Results: The change CGMGdays1-3 was significantly lower following TA-ER vs TAcs (14.7 vs 33.9 mg/dl, least-squares-mean-difference [95% CI]: -19.2 [-38.0, -0.4]; P = 0.0452). The percentage of time over days 1-3 that CGMG was in the target glycaemic range (70-180 mg/dl) was numerically greater for TA-ER (63.3%) vs TAcs (49.7%), and that CGMG was >180 mg/dl was lower for TA-ER (34.5%) vs TAcs (49.9%). Non-glycaemic adverse events were mild and comparable between groups.

Conclusion: TA-ER may enable intra-articular corticosteroid treatment with minimal blood glucose disruption in patients with knee osteoarthritis and type 2 diabetes mellitus.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT02762370" title="See in ClinicalTrials.gov">NCT02762370.

Figures

Fig . 1
Fig. 1
Trial profile a3 patients were randomized correctly, but received the incorrect treatment. b1 patient was not willing to return for the final week 6 visit, but did complete the study through day 15. TAcs: triamcinolone acetonide crystalline suspension; TA-ER: triamcinolone acetonide extended-release injectable suspension.
Fig . 2
Fig. 2
Mean average hourly CGMG levels (FAS; n = 33) CGMG: continuous glucose monitoring-measured glucose; FAS: full analysis set; LSM: least squares mean; SE: standard error; TAcs: triamcinolone acetonide crystalline suspension; TA-ER: triamcinolone acetonide extended-release.
Fig . 3
Fig. 3
Changes in blood glucose profile for days 1–3 with TA-ER vs TAcs (A) Mean change from baseline to days 1–3 for the average CGMG. (B) Percentage of time in target glycaemic range for hourly the average CGMG during days 1–3 (FAS; N = 33). CGMG: continuous glucose monitoring-measured glucose; FAS: full analysis set; LSM: least squares mean; SE: standard error; TAcs: triamcinolone acetonide crystalline suspension; TA-ER: triamcinolone acetonide extended-release.

References

    1. Robinson WH, Lepus CM, Wang Q. et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12:580–92.
    1. Abate M, Schiavone C, Salini V, Andia I.. Management of limited joint mobility in diabetic patients. Diabetes Metab Syndr Obes 2013;6:197–207.
    1. Louati K, Vidal C, Berenbaum F, Sellam J.. Association between diabetes mellitus and osteoarthritis: systematic literature review and meta-analysis. RMD Open 2015;1:e000077.
    1. Hawker GA, Croxford R, Bierman AS. et al. Osteoarthritis-related difficulty walking and risk for diabetes complications. Osteoarthritis Cartilage 2017;25:67–75.
    1. Douglas RJ. Corticosteroid injection into the osteoarthritic knee: drug selection, dose, and injection frequency. Int J Clin Pract 2012;66:699–704.
    1. Derendorf H, Möllmann H, Grüner A, Haack D, Gyselby G.. Pharmacokinetics and pharmacodynamics of glucocorticoid suspensions after intra-articular administration. Clin Pharmacol Ther 1986;39:313–7.
    1. Zhang W, Moskowitz RW, Nuki G. et al. OARSI recommendations for the management of hip and knee osteoarthritis, part II: oARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16:137–62.
    1. Habib GS. Systemic effects of intra-articular corticosteroids. Clin Rheumatol 2009;28:749–56.
    1. Habib G, Bashir M, Jabbour A.. Increased blood glucose levels following intra-articular injection of methylprednisolone acetate in patients with controlled diabetes and symptomatic osteoarthritis of the knee. Ann Rheum Dis 2008;67:1790–1.
    1. Habib GS, Miari W.. The effect of intra-articular triamcinolone preparations on blood glucose levels in diabetic patients: a controlled study. J Clin Rheumatol 2011;17:302–5.
    1. Habib G, Khazin F, Chernin M.. Continuous blood glucose monitoring in a patient with type 2 diabetes who underwent intraarticular betamethasone injection for knee osteoarthritis. Arthritis Rheumatol 2014;66:230.
    1. Conaghan PG, Cohen S, Berenbaum F. et al. Brief report: a phase IIb trial of a novel extended-release microsphere formulation of triamcinolone acetonide for intraarticular injection in knee osteoarthritis. Arthritis Rheumatol 2018;70:204–11.
    1. Conaghan PG, Hunter DJ, Cohen SB. et al. Effects of a single intra-articular injection of a microsphere formulation of triamcinolone acetonide on knee osteoarthritis pain: a double-blinded, randomized, placebo-controlled, multinational study. J Bone Joint Surg Am 2018;100:666–77.
    1. Kraus VB, Aazami HA, Mehra P. et al. Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA). Osteoarthritis Cartilage 2018;26:34–42.
    1. Altman R, Asch E, Bloch D. et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheumatol 1986;29:1039–49.
    1. Damiano ER, McKeon K, El-Khatib FH. et al. A comparative effectiveness analysis of three continuous glucose monitors: the Navigator, G4 Platinum and Enlite. J Diabetes Sci Technol 2014;8:699–708.
    1. Ekhlaspour L, Mondesir D, Lautsch N. et al. Comparative accuracy of 17 point-of-care glucose meters. J Diabetes Sci Technol 2017;11:558–66.
    1. American Diabetes Association. Position statement 5. Glycemic targets. Diabetes Care 2016;39:S39–46.
    1. Bodick N, Lufkin J, Willwerth C. et al. An intra-articular, extended-release formulation of triamcinolone acetonide prolongs and amplifies analgesic effect in patients with osteoarthritis of the knee: a randomized clinical trial. J Bone Joint Surg Am 2015;97:877–88.
    1. Russell SJ, Sala R, Conaghan PG. et al. In type 2 diabetes mellitus patients with knee osteoarthritis intra-articular injection of FX006 (extended release triamcinolone) is associated with reduced BG elevation vs standard triamcinolone: a randomized, blinded, parallel-group study. Diabetes. 2017;66(Suppl 1):A289(abstract).

Source: PubMed

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