Pharmacokinetics and pharmacodynamics of glucocorticoid suspensions after intra-articular administration

135

110

Objective. To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double-blind, placebocontrolled trial.Methods. Fifty-two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n ‫؍‬ 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n ‫؍‬ 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100-mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100-mm VAS), and Short Form 36 (SF-36) quality of life indices. Analyses were based on the intent-to-treat principle.Results. The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P ‫؍‬ 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P ‫؍‬ 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P ‫؍‬ 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P ‫؍‬ 0.005), and SF-36 physical component scores (P ‫؍‬ 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the frequency of adverse events between groups.Conclusion. This placebo-controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA, with benefits lasting up to 3 months in many cases. Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification.Osteoarthritis (OA) affects all vertebrates, and the prevalence of the disease increases exponentially with age. Estimates of the prevalence of hip OA in humans range from 2% at age 35 years to 35% at age 85 years or older (1), and autopsies have shown that cartilage degeneration can be detected in patients as early as the second decade of life (2). A disease prevalence estimate of 3% among North Americans older than age 55 years has been commonly quoted, but this may well be an underestimate of the true burden of hip OA in the general population (3,4). The prevalence of the disease has significant fiscal implications, since it has

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Steroid injection for osteoarthritis of the hip: A randomized, double‐blind, placebo‐controlled trial

Lambert

Hutchings

Grace

et al. 2007

135

110

“…Although there is no absolute proof that this decrease in enzyme activity was the result of steroid therapy, it is possible that the pharmacologic effects of these agents may last longer than do their direct effects in the joint. This could vary from a few hours to a few weeks, depending on their chemical composition (19,20). It might explain why the clinical improvement in patients treated with intraarticular steroids may last for many months (20).…”

Section: Discussionmentioning

confidence: 99%

Proteoglycan‐degrading acid metalloprotease activity in human osteoarthritic cartilage, and the effect of intraarticular steroid injections

Pelletier¹,

Martel‐Pelletier²,

Cloutier³

et al. 1987

Cartilage samples from both the immediate and remote lesion areas were obtained from the tibia1 plateaus of 21 patients with osteoarthritis, and were subjected to histologic and enzymatic study. There was a frequent loss of pericellular metachromatic staining in the OA cartilage. Seven patients had received intraarticular injections of steroids, and in 21 % of those cartilage samples, a pericellular halo was seen. This halo was seen in 71 % of patients who had not received steroid injections. The total acid metalloprotease activity was increased more than twofold in specimens from OA lesions and in those samples graded moderate, as compared with age-matched control cartilages. These differences were greater when the specimens from patients who had received steroid therapy were excluded from the data. The cartilage specimens from steroid-treated patients were not significantly different from those of controls with respect to the enzyme activity in the lesions or in cartilage with moderate disease. The active form of the protease was suppressed by steroids. In samples from patients who did not receive steroid injections and who had a moderate grade of OA, a significantly elevated level of the active protease was present, as compared with control samples. Those samples graded moderate which came from patients who received steroid treatments showed no difference in the active protease level versus that of controls. Our results are consistent with the hypothesis that acid metalloprotease activity is involved in the degradation of the cartilage matrix in OA. Since the protease retains a significant fraction (40%) of its activity at neutral pH, its physiologic role might occur either at acid pH or at neutral pH. The halo surrounding the chondrocytes (the result of a local loss of proteoglycan) might be related to the action of this enzyme. Preliminary evidence has suggested that steroids reduce cartilage enzyme activity. Address reprint requests to J. p. Pelletier, MD, Unit6 des Maladies Rhumatismales, HGpital Notre-Dame, 1560 rue Sherbrooke Est, Montreal, Quebec, Canada H2L 4K8.vised form November 11, 1986. tent (1). Recent reports by Sachs et a1 (2) and Goldberg et (3) describe types Of changes in metachromatic staining. Type A is characterized by a lack of perkellular staining, so that a halo appearance is present around the lacunae. The remainder Of the intertenitorial matrix has norma] metachromatic staining. The

“…Studies on patients have shown that, due to its lower solubility, T H is absorbed more slowly than triamcinolone acetonide, and that levels in the synovial fluid are maintained for over 2 weeks (26). Because of its prolonged action and the positive results demonstrated in other models of OA, it was of the utmost importance to determine the effects of TH in the dog model, which closely mimics human OA.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the pond‐nuki dog model of osteoarthritis

Pelletier

Martel‐Pelletier

1989

147

The in vivo effects of corticosteroids on osteoarthritic (OA) lesions were examined in 12 dogs in which the anterior cruciate ligament had been sectioned. Six were treated with oral prednisone and 6 were treated with intraarticular (IA) injections of triamciaolone hexacetonide (TH), at surgery and 4 weeks later. Twelve other operated dogs received no treatment. All dogs were killed 8 weeks postsurgery. Four of 15 normal control dogs received IA TH injections. Operated untreated dogs developed significant cartilage lesions on the femoral condyles and tibial plateaus with prominent osteophytes. Operated dogs treated orally or with IA injections had a significant reduction in osteophyte size.Cartilage erosions on femoral condyles were observed in 25% of the untreated dogs, 8% of the dogs receiving oral prednisone, and none of the dogs receiving IA TH. In both groups of treated dogs, the size of the tibial plateau lesions was significantly reduced compared with the operated untreated dogs. Histologically, corticosteroids significantly reduced the severity of OA structural changes of the cartilage on both medial and lateral femoral condyles and tibial plateaus in operated animals, with the exception of the lateral plateaus of those