Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate

Metroplex Clinical Research Center, Dallas, Texas, USA.
Annals of the rheumatic diseases (Impact Factor: 9.27). 06/2010; 69(6):1158-61. DOI: 10.1136/ard.2009.119222
Source: PubMed

ABSTRACT Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors.
To assess structural damage progression through 2 years.
Intention-to-treat patients with one post-baseline radiograph (rituximab n=281; placebo n=187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received > or = 1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104.
At week 104, significantly lower changes in TSS (1.14 vs 2.81; p<0.0001), erosion score (0.72 vs 1.80; p<0.0001) and joint space narrowing scores (0.42 vs 1.00; p<0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years.
Rituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitors.

Download full-text


Available from: Paul Emery, Jun 21, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a chronic, destructive, autoimmune joint disease characterized by elevated levels of proinflammatory cytokine production. Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate. Synovial fluid of RA patients exhibits significantly higher levels of S1P than their non-inflammatory osteoarthritis counterparts. SphK blockade suppresses cytokines and MMP-9 release in RA peripheral blood mononuclear cells. In addition, downregulation of SphK1 either through a specific siRNA approach or transgenic human TNF-α SphK1-deficient mice (hTNF-α/SphK1(-/-)) exhibit significantly less synovial inflammation and joint pathology. By contrast, SphK2 modulation leads to disease exacerbation. These results clearly demonstrate that such anti- and proinflammatory potential of SphK1/2 modulation may alter the outcome in RA synovitis and raises the possibility that drugs that specifically target SphK1 activity may play a beneficial role in the treatment of RA and other autoimmune rheumatic diseases.
    Future medicinal chemistry 04/2012; 4(6):727-33. DOI:10.4155/fmc.12.28 · 4.00 Impact Factor
  • The Journal of Rheumatology 05/2013; 40(5):732-733. DOI:10.3899/jrheum.130175 · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The approval - several years ago - of the first tumour necrosis factor-α (TNF-α) inhibitor for the management of rheumatoid arthritis launched a new era in the therapeutics of rheumatology. Since then an almost cataclysmic discovery of new treatment targets and corresponding biologic agents ensued. Nowadays, the rheumatologist and the rheumatologic patient have the luxury of several immune modulators available to successfully treat the majority of patients with RA or other inflammatory arthritides and conditions. In this review we focus on a discussion of the approved immune modulators/biologic agents available for the treatment of rheumatoid arthritis. We also present an overview of agents under development. For the immune modulators discussed, we describe their mechanism of action and summarise initial data and recent updates on efficacy and safety.
    Best practice & research. Clinical rheumatology 12/2011; 25(6):873-89. DOI:10.1016/j.berh.2011.11.003 · 3.06 Impact Factor