MIljenko,
Large part of this broad arthritis population is Osteoarthritis.
Agreed. But it is interesting to note that Vertex thinks that their ICE inhibitor will show some efficacy in OA as well, and a re currently running a Phase II trial in OA.
By the way, a recent trial has showed that the nutritional supplement glucosamine is likely effective in OA:
Arch Intern Med 2002 Oct 14;162(18):2113-23 Related Articles, Links
Glucosamine Sulfate Use and Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized, Placebo-Controlled, Double-blind Study.
Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC.
Institute of Rheumatology, Na Slupi 4, 128 50 Praha 2, Czech Republic. pavelka@revma.cz
BACKGROUND: Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression. The aim of this randomized, placebo-controlled trial was to determine whether long-term (3-year) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis, as previously suggested. METHODS: Two hundred two patients with knee osteoarthritis (using American College of Rheumatology criteria) were randomized to receive oral glucosamine sulfate, 1500 mg once a day, or placebo. Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint, and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC (Western Ontario and McMaster Universities). RESULTS: Osteoarthritis was of mild to moderate severity at enrollment, with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was -0.19 mm (95% confidence interval, -0.29 to -0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulfate use (0.04 mm; 95% confidence interval, -0.06 to 0.14 mm), with a significant difference between groups (P =.001). Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings (>0.5 mm): 5% vs 14% (P =.05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulfate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness subscales. Safety was good and without differences between groups. CONCLUSION: Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis, possibly determining disease modification.
The mode of glucosamine's action is still unclear. One recent idea is that it modifies IL1-beta pathways and inhibits NF-Kappa B:
FEBS Lett 2002 Jan 16;510(3):166-70 Related Articles, Links
Glucosamine modulates IL-1-induced activation of rat chondrocytes at a receptor level, and by inhibiting the NF-kappa B pathway.
Gouze JN, Bianchi A, Becuwe P, Dauca M, Netter P, Magdalou J, Terlain B, Bordji K.
UMR 7561, CNRS-Universite Henri Poincare-Nancy I, Physiopathologie et Pharmacologie Articulaires, Faculte de Medecine, Vandoeuvre-les-Nancy, France.
We recently reported that glucosamine reversed the decrease in proteoglycan synthesis and in UDP-glucuronosyltransferase I mRNA expression induced by interleukin-1 beta (IL-1 beta) [Arthritis Rheum. 44 (2001) 351-360]. In the present work, we show that glucosamine does not exert the same effects when chondrocytes were stimulated with reactive oxygen species (ROS). In order to better understand its mechanism of action, we determined if glucosamine could prevent the binding of IL-1 beta to its cellular receptors or could interfere with its signaling pathway at a post-receptor level. Addition of glucosamine to rat chondrocytes treated with IL-1 beta or with ROS decreased the activation of the nuclear factor kappa B, but not the activator protein-1. After treatment with IL-1 beta, glucosamine increased the expression of mRNA encoding the type II IL-1 beta receptor. These results emphasize the potential role of two regulating proteins of the IL-1 beta signaling pathway that could account for the beneficial effect of glucosamine in osteoarthritis.
(Vertex's ICE drug is also an IL-1 beta modulator, with effects also on IL-18).
BTW, I disagree with you on once-a-month SC injections vs. daily oral. Tens of millions of people already take daily oral therapy for RA and OA. If something with greater efficacy came along, why wouldn't they use it willingly?
Peter |
