Rheumatoid Arthritis: Lipsky P

Kavanaugh A, Lipsky P. · Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Tex., USA. · Curr Dir Autoimmun. · Pubmed #11791469 No free full text.

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Kavanaugh A, St Clair EW, McCune WJ, Braakman T, Lipsky P. · University of Texas, Southwestern Medical Center, Dallas, USA. · J Rheumatol. · Pubmed #10782805 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and efficacy of single and multiple doses of a chimeric anti-TNF-alpha monoclonal antibody (infliximab) in patients with rheumatoid arthritis (RA) who had active disease despite therapy with methotrexate (MTX). METHODS: Twenty-eight patients with active RA despite receiving therapy with 10 mg/week of MTX were randomized to receive a single, blinded infusion of either placebo or 5, 10, or 20 mg/kg infliximab. Twenty-three patients who completed the blinded study entered an open, multiple dose extension study in which they received up to 3 additional infusions of 10 mg/kg infliximab at Weeks 12, 20, and 28. Safety, efficacy, and pharmacokinetics were evaluated during the blinded and open trial. RESULTS: There were no serious infusion related reactions. In the blinded phase, 17 (81.0%) of 21 patients receiving infliximab achieved an American College of Rheumatology (ACR) 20% response at some point during the 12 weeks of followup compared to one (14.3%) of 7 patients receiving placebo (p = 0.003). Clinical improvement was evident by the first week and was sustained through Week 12. For the 19 patients who received infliximab during the blinded part of the trial and continued into the open label trial, 53% maintained an ACR 20% response with multiple infusions of 10 mg/kg infliximab through Week 40. Three patients withdrew from the trial during the open continuation phase because of adverse events: cellulitis, infusion related dizziness and headache, and vasculitic rash. Infliximab in doses of 5 to 20 mg/kg had a mean terminal half-life ranging from 9 to 12 days and was detectable in sera from most patients 8 to 12 weeks after dosing. CONCLUSION: Infliximab is generally well tolerated during 40 weeks of therapy. A single infusion of 5 to 20 mg/kg infliximab significantly decreases the signs and symptoms of RA compared to placebo in patients with active disease receiving MTX. Multiple doses of infliximab produce sustained clinical benefit for up to 40 weeks.

Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P. · The Kennedy Institute of Rheumatology and The Imperial College School of Medicine at Charing Cross Hospital, London, UK. · Lancet. · Pubmed #10622295 No free full text.

Abstract: BACKGROUND: Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate. METHODS: In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks. FINDINGS: At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group. INTERPRETATION: During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate.

Yao L, Magalnick M, Wilson M, Lipsky P, Goldbach-Mansky R. · Diagnostic Radiology Department, National Institutes of Health, 10 Center Drive, Room 1C640, Bethesda, MD 20892-1182, USA. · AJR Am J Roentgenol. · Pubmed #16861538 links to  free full text

Abstract: OBJECTIVE: The purpose of this study was to establish the relative predictive value of T2-weighted and contrast-enhanced T1-weighted MRI techniques for bone erosions that are evident on CT. Because it is known that MRI depicts abnormalities in the periarticular bone of patients with rheumatoid arthritis, we wanted to compare the outcomes of T2-weighted versus contrast-enhanced T1-weighted MRI techniques. MATERIALS AND METHODS: Eleven patients with rheumatoid arthritis underwent CT imaging of their most affected wrist. Fast spin-echo T2-weighted MR images were then acquired with spectral fat saturation. Enhanced T1-weighted spin-echo images acquired before and after IV administration of gadopentetate dimeglumine were used to determine the percent enhancement. Imaging examinations were scored for 15 anatomic zones. The CT score was based on cortical bone erosion. The MR score was based on periarticular bone marrow signal alteration. RESULTS: Both T2-weighted MR images with spectral fat saturation and enhanced T1-weighted images were concordant for the presence or absence of bone abnormalities in 122 of 165 zones (74%). Of the 43 zones that were discordant for an abnormality by the two MR techniques, the T2-weighted images were positive in five zones, and enhanced T1-weighted images were positive in 38 zones (p < 0.001). Of the 43 zones that were discordant by the two MR techniques, enhanced T1-weighted images were concordant with CT in 20 zones, whereas the T2-weighted images were concordant with CT in 23 zones (p = 0.76). A greater proportion of lesions detected by the T2-weighted images were "edema-like" signal patterns. CONCLUSION: In rheumatoid arthritis, contrast-enhanced T1-weighted MRI depicts more periarticular bone abnormalities than fat-suppressed T2-weighted MRI. These MR techniques are equally predictive of frank, erosive disease that is evident on CT.

van der Heijde D, Simon L, Smolen J, Strand V, Sharp J, Boers M, Breedveld F, Weisman M, Weinblatt M, Rau R, Lipsky P. · Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #11954017 No free full text.

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Sims G, Lipsky P. · No affiliation provided · Arthritis Rheum. · Pubmed #17330259 links to  free full text

This publication has no abstract.