Arthritis Chronicle

This article comes from P Emery and friends from the Shaw lab at Chapel Allerton Hospital in Leeds, England.

OBJECTIVE: To examine the efficacy and safety of different rituximab doses plus methotrexate (MTX), with or without glucocorticoids, in patients with active rheumatoid arthritis resistant to disease-modifying antirheumatic drugs (DMARDs), including biologic agents.

METHODS: A total of 465 patients were randomized into 9 treatment groups: 3 rituximab groups (placebo [n = 149], 500 mg [n = 124], or 1,000 mg [n = 192] on days 1 and 15) each also taking either placebo glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks. All patients received MTX (10-25 mg/week); no other DMARDs were permitted.

RESULTS: Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < 0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < 0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < 0.05). Changes in the Disease Activity Score in 28 joints (-1.79, -2.05, -0.67; P < 0.0001) and moderate to good responses on the European League Against Rheumatism criteria (P < 0.0001) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo.

CONCLUSION: Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active rheumatoid arthritis. The primary end point (ACR20 response) was independent of glucocorticoids, although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion.

The full article can be found in the April edition of arthritis and rheumatism starting on page number 1390. The pubmed number is 16649186

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This article is from the Botnor Research centre at Oxford University in the UK, it was written by J Edwards and colleagues from the Sabokbar lab. It’s full title is LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis.

OBJECTIVE: Human osteoclast formation from mononuclear phagocyte precursors involves interactions between tumor necrosis factor ligand superfamily members and their receptors. LIGHT is a transmembrane protein expressed and shed from the surface of activated T cells. Since activated T cells have been implicated in osteoclastogenesis in rheumatoid arthritis, this study sought to determine whether LIGHT can regulate RANKL/cytokine-induced osteoclast formation, to identify the mechanism by which LIGHT influences osteoclastogenesis, and to investigate the presence of LIGHT in the serum of rheumatoid arthritis patients.

METHODS: The effect of LIGHT on human and murine osteoclast formation was assessed in the presence and absence of neutralizing reagents to known osteoclastogenic factors. Serum levels of LIGHT in rheumatoid arthritis patients were measured by enzyme-linked immunosorbent assay.

RESULTS: In the presence and absence of RANKL, LIGHT induced osteoclast formation from both human peripheral blood mononuclear cells and murine macrophage precursors, in a dose-dependent manner, whereas no inhibition was observed by adding osteoprotegerin, RANK:Fc, tumor necrosis factor alpha, or interleukin-8 or by blocking the LIGHT receptors herpesvirus entry mediator or lymphotoxin beta receptor. However, formation of osteoclasts was significantly decreased by the soluble decoy receptor for LIGHT, DcR3, and by blocking antibodies to the p75 component of the tumor necrosis factor  receptor. A significant increase in LIGHT levels in the serum of rheumatoid arthritis patients compared with normal controls was also noted.

CONCLUSION: Our results indicate that LIGHT promotes RANKL-mediated osteoclastogenesis and that it can induce osteoclast formation by a mechanism independent of RANKL. The increased concentration of LIGHT in patients with rheumatoid arthritis raises the possibility that LIGHT may play a role in immunopathogenic conditions that are associated with localized or systemic bone loss.

This is from the April edition of Arthritis and rheumatism it is available under pubmed number 16649193 It starts on page 1451 issue 28;54(5)

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