Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial.

Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial.

MedLine Citation:	PMID: 18438830 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	OBJECTIVE: RANKL is essential for osteoclast development, activation, and survival. Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL, inhibiting its activity. The aim of this multicenter, randomized, double-blind, placebo-controlled, phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis (RA) receiving methotrexate treatment. METHODS: RA patients received subcutaneous placebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) injections every 6 months for 12 months. The primary end point was the change from baseline in the magnetic resonance imaging (MRI) erosion score at 6 months. RESULTS: At 6 months, the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P = 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P = 0.007) than in the placebo group (mean change 1.75). A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group (P = 0.019) as compared with placebo, and at 12 months, both the 60-mg (P = 0.012) and the 180-mg (P = 0.007) denosumab groups were significantly different from the placebo group. Denosumab caused sustained suppression of markers of bone turnover. There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity. Rates of adverse events were comparable between the denosumab and placebo groups. CONCLUSION: Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months, with no increase in the rates of adverse events as compared with placebo.

Authors:	Stanley B Cohen; Robin K Dore; Nancy E Lane; Peter A Ory; Charles G Peterfy; John T Sharp; Désirée van der Heijde; Lifen Zhou; Wayne Tsuji; Richard Newmark;
Publication Detail:	Type: Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Journal Detail:	Title: Arthritis and rheumatism Volume: 58 ISSN: 0004-3591 ISO Abbreviation: Arthritis Rheum. Publication Date: 2008 May
Date Detail:	Created Date: 2008-05-27 Completed Date: 2008-06-23 Revised Date: 2009-02-17
Medline Journal Info:	Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States
Other Details:	Languages: eng Pagination: 1299-309 Citation Subset: AIM; IM
Affiliation:	Metroplex Clinical Research Center, Dallas, Texas 75235, USA. Scohen@arthdocs.com
Data Bank Information
Bank Name/Acc. No.:	ClinicalTrials.gov/NCT00095498
Export Citation:	APA/MLA Format Download EndNote Download BibTex
MeSH Terms
Descriptor/Qualifier:	Antibodies, Monoclonal / therapeutic use* Antirheumatic Agents / therapeutic use Arthritis, Rheumatoid / diagnosis, drug therapy, metabolism* Bone Density / drug effects* Bone and Bones / drug effects, metabolism Double-Blind Method Female Humans Magnetic Resonance Imaging Male Methotrexate / therapeutic use Middle Aged RANK Ligand / therapeutic use* Time Factors
Chemical
Reg. No./Substance:	0/Antibodies, Monoclonal; 0/Antirheumatic Agents; 0/RANK Ligand; 59-05-2/Methotrexate; 615258-40-7/denosumab
Investigator
Investigator/Affiliation:	Christopher Atkins / ; Andre Beaulieu / ; Mary Bell / ; Stephen Bookbinder / ; Alan Brodsky / ; Atulya Deodhar / ; Gino Divittorio / ; Alan Fishman / ; Eric Grant / ; Brian Grimmett / ; Boulous Haraoui / ; Joseph Huffstutter / ; Eric Hurd / ; Alan Kaell / ; Arthur Kavanaugh / ; Jonathan Kay / ; Edward Keystone / ; Majed Khraishi / ; Michael Kohen / ; Mark Iannini / ; David Mandel / ; Robert McKendry / ; Phillip Mease / ; Larry Moreland / ; Sara Newell / ; William Palmer / ; Jeffrey Poiley / ; Boris Ratiner / ; Christopher Ritchlin / ; Joy Schechtman / ; Michael Schiff / ; William Shergy / ; H Arthur Silverman / ; Gary Sultany / ; Hyman Tannenbaum / ; Robert Trapp / ; Peter Valen / ; Michel Zummer /
Comments/Corrections
Comment In:	Nat Clin Pract Rheumatol. 2008 Dec;4(12):634-5 [PMID: 18839011 ] Curr Rheumatol Rep. 2008 Oct;10(5):381-2 [PMID: 18817642 ]

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