Rheumatoid Arthritis: Bankhurst AD

Kremer JM, Weinblatt ME, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Jackson CG, Atkins KM, Feng A, Burge DJ. · The Center for Rheumatology, Albany, New York 12206, USA. · Arthritis Rheum. · Pubmed #12794815 links to  free full text

Abstract: OBJECTIVE: To observe the long-term safety and efficacy of combination therapy with etanercept and methotrexate in patients with rheumatoid arthritis (RA), and to determine whether the addition of etanercept allowed reductions in methotrexate or corticosteroid dosages while maintaining a clinical response. METHODS: Patients with RA who received methotrexate plus etanercept in a previous randomized, placebo-controlled trial were offered the opportunity to enroll in an open-label extension study for further evaluation of treatment with etanercept and methotrexate. RESULTS: Seventy-nine of the 89 patients in the original blinded study enrolled in the extension study, and 65 of these patients continue in the study. Patients have received etanercept therapy for up to 47 months (median 44 months). The types and rate of adverse events noted during the extension trial were similar to those observed in the controlled trial. At the 3-year assessment, 77% of the 57 patients available for evaluation met American College of Rheumatology 20% (ACR20) criteria for improvement in RA, 47% met the ACR50 criteria, and 23% met the ACR70 criteria. Of the 36 patients assessed at 3 years in the extension study, 30 (83%) were able to decrease their dosages of corticosteroids, and 20 (56%) were able to discontinue corticosteroid therapy. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%). CONCLUSION: In this observational continuation study, the addition of etanercept to background methotrexate provided sustained clinical benefit over a median period of 44 months. With etanercept therapy, there were trends toward dosage reduction or discontinuation of methotrexate and corticosteroids, without apparent worsening of ACR response rates. Compared with the controlled trial, no increases in the rate of adverse events were observed.

Bankhurst AD. · Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque 87131-5271, USA. · Clin Exp Rheumatol. · Pubmed #10589361 No free full text.

Abstract: Tumor necrosis factor (TNF) is a major proinflammatory cytokine in the rheumatoid joint. TNF activity can be neutralized by administration of a recombinant version of its soluble p75 TNF receptor linked to the Fc portion of human immunoglobulin IgG1 (etanercept). The present study examined the combination of etanercept with methotrexate (MTX) in a group of patients with rheumatoid arthritis (RA) who had persistent activity despite monotherapy with MTX. The etanercept-MTX group had a significantly better outcome than the placebo-MTX group using American College of Rheumatology (ACR) criteria. At 6 months, 71% of the patients in the etanercept-MTX group had an ACR 20% response (versus 27% in the placebo-MTX group). In the etanercept-MTX group, 39% had an ACR 50% response (versus 3% in the placebo-MTX group), and 15% in the etanercept-MTX group versus 0% in the placebo-MTX group met the robust ACR 70% response. The present study indicates that etanercept is a novel and robust drug in combination with MTX for the treatment of RA.

Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, Jackson CG, Lange M, Burge DJ. · Brigham and Women's Hospital, Boston, MA 02115, USA. · N Engl J Med. · Pubmed #9920948 links to  free full text

Abstract: BACKGROUND: Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate. METHODS: In a 24-week, double-blind trial, we randomly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week (or as low as 10 mg per week for patients unable to tolerate higher doses) to receive either etanercept (25 mg) or placebo subcutaneously twice weekly while continuing to receive methotrexate. The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20) at 24 weeks. RESULTS: The addition of etanercept to methotrexate therapy resulted in rapid and sustained improvement. At 24 weeks, 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria (P<0.001); 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria (for a 50 percent improvement) (P<0.001). Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity. The only adverse events associated with etanercept were mild injection-site reactions, and no patient withdrew from the study because of adverse events associated with etanercept. CONCLUSIONS: In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone.

Bankhurst AD, Husby G, Williams RC. · Department of Medicine, University of New Mexico School of Medicine, Alburquerque, New Mexico 87131, USA. · Arthritis Rheum. · Pubmed #18240218 links to  free full text

Abstract: Synovial tissues from 5 patients with rheumatoid arthritis (RA) were examined immunofluorescence microscopy for the presence of lymphocytes with either bone marrow-derived (B) or thymus-derived (T) surface markers. Five synovial tissues with severe to mild lymphocytic infiltrations by bright field microscopy were examined in parallel with immunofluorescence. B cells were identified with a pepsin-digested fluoresceinated anti-F (ab')2 antiserum and T cells were detected with a specific rabbit and anti-T lymphocyte antiserum. By these techniques 75-90% of the lymphocytes in these frozen sections were identified as T cells. Cell suspensions were also prepared by collagenase digestion of two of the five synovial tissues. The lymphocytes in these cell suspensions were predominantly T lymphocytes (78-85%) as shown by their ability to form spontaneous rosettes with sheep erythrocytes (E rosettes).