Inhibition of Tumor Necrosis Factor

- Discussion:
    - these agents bind TNF and block inflammation by inhibiting the subsequent effects of this cytokine;
    - infliximab:
          - a chimeric monoclonal antibody against TNF-(alpha)
          - variable region of a murine antibody grafted to the constant region of a human antibody;
          - given intravenously every two months;
          - in the report by Lipsky PE, et al. (2000), the authors treated 428 patients
                 who had active RA despite methotrexate therapy with placebo or infliximab;
                 - IV doses of 3 or 10 mg / kg of body weight q 4 or 8 weeks in combo w/ oral methotrexate for 54 weeks;
                 - the authors noted the combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8% vs. 17.0%; P<0.001);
                 - the quality of life was also significantly better with infliximab plus methotrexate than w/ methotrexate alone;
                 - radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6; P<0.001);
                 - radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response;
                 - the authors concluded the patients with persistently active RA despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage.
                 - ref: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. 
    - etanercept (enbrel)
          - soluble receptor
          - dimer consisting of a TNF receptor joined to the Fc domain of a human IgG1 molecule;
          - given subcutaneously twice a week;
          - in the report by Bathon JM, et al (2000), the authors followed 632 patients with early RA with either twice-weekly subQ etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months.
                  - as compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20%, 50%, and 70% improvement in disease activity during the first six months (P<0.05)
                  - among patients who received the 25-mg dose of etanercept, 72% had no increase in the erosion score, as compared with 60% of patients in the methotrexate group (P=0.007). This group of patients also had fewer adverse events (P=0.02) and fewer infections (P=0.006) than the group that was treated with methotrexate
                  - A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis

Tumor necrosis factor blockers in rheumatoid arthritis.

Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Tuesday, August 21, 2012 2:33 pm