Rheumatoid Arthritis: Cush J

Furst DE, Cush J, Kaufmann S, Siegel J, Kurth R. · UCLA Medical School, Los Angeles, USA Presbyterian Hospital, Dallas, USA. · Ann Rheum Dis. · Pubmed #12379625 links to  free full text

This publication has no abstract.

Kremer J, Genovese M, Cannon GW, Caldwell J, Cush J, Furst DE, Luggen M, Keystone E, Bathon J, Kavanaugh A, Ruderman E, Coleman P, Curtis D, Kopp E, Kantor S, Weisman M, Waltuck J, Lindsley HB, Markenson J, Crawford B, Fernando I, Simpson K, Strand V. · Center for Rheumatology, Albany, New York 12206, USA. · J Rheumatol. · Pubmed #15290730 No free full text.

Abstract: OBJECTIVE: To obtain additional safety and efficacy data on leflunomide (LEF) treatment in combination with methotrexate (MTX) therapy in an open-label extension study in patients with rheumatoid arthritis (RA). METHODS: Following a 24 week, randomized, double-blind trial of adding placebo (PLA) or LEF to stable MTX therapy, patients could enter a 24 week extension. Subjects randomized to LEF and MTX continued treatment [(LEF/LEF) + MTX]. Subjects randomized to PLA and MTX switched to LEF (10 mg/day, no loading dose) and MTX [(PLA/LEF) + MTX]. The double-blind regarding initial randomization was maintained. RESULTS: For subjects in the extension phase, American College of Rheumatology 20% (ACR20) responder rates for the (LEF/LEF) + MTX group were maintained from Week 24 (57/96, 59.4%) to Week 48 (53/96, 55.2%). ACR20 responder rates improved in patients switched to LEF from PLA at Week 24 [(PLA/LEF) + MTX] from 25.0% (24/96) at Week 24 to 57.3% (55/96) at Week 48. Patients in the extension who switched from PLA to LEF without a loading dose exhibited a lower incidence of elevated transaminases compared to patients initially randomized to LEF. Diarrhea and nausea were less frequent during the open-label extension in patients who did not receive a LEF loading dose. CONCLUSION: Response to therapy was maintained to 48 weeks of treatment in patients who continued to receive LEF and MTX during the extension. Importantly, ACR20 response rates after 24 weeks of LEF therapy were similar between patients switched from PLA to LEF without loading dose, and those who received a loading does of LEF (100 mg/day x 2 days) at randomization. Fewer adverse events were reported in patients switched to LEF without a loading dose.

Davis JC, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W, Anonymous00203. · University of California, San Francisco, CA 94143, USA. · Arthritis Rheum. · Pubmed #14613288 links to  free full text

Abstract: OBJECTIVE: To determine the safety and efficacy of etanercept in a multicenter, randomized, placebo-controlled, double-blind trial of adults with moderate to severe active ankylosing spondylitis (AS). METHODS: Patients (n = 277) were treated with either etanercept 25 mg (n = 138) or placebo (n = 139) subcutaneously twice weekly for 24 weeks. The primary outcome measures were the percentages of patients achieving the Assessments in Ankylosing Spondylitis 20% response (ASAS20) at weeks 12 and 24. Other outcome measures included the percentage of patients achieving higher ASAS responses, and the safety of etanercept in patients with AS. All outcome measures were assessed at 2, 4, 8, 12, and 24 weeks. RESULTS: Treatment with etanercept resulted in dramatic improvement. The ASAS20 was achieved by 59% of patients in the etanercept group and by 28% of patients in the placebo group (P < 0.0001) at week 12, and by 57% and 22% of patients, respectively, at week 24 (P < 0.0001). All individual ASAS components, acute-phase reactant levels, and spinal mobility measures were also significantly improved. The safety profile of etanercept was similar to that reported in studies of patients with rheumatoid arthritis or psoriatic arthritis. The only adverse events that occurred significantly more often in the etanercept group were injection-site reactions, accidental injuries, and upper respiratory tract infections. CONCLUSION: Etanercept is a highly effective and well tolerated treatment in patients with active AS.

Cohen S, Hurd E, Cush J, Schiff M, Weinblatt ME, Moreland LW, Kremer J, Bear MB, Rich WJ, McCabe D. · Department of Rheumatology, St. Paul Medical Center, Dallas, Texas 75235, USA. · Arthritis Rheum. · Pubmed #11920396 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for > or = 3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12. RESULTS: A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses. CONCLUSION: In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone.

Hansen KE, Cush J, Singhal A, Cooley DA, Cohen S, Patel SR, Genovese M, Sundaramurthy S, Schiff M. · University of Wisconsin, Madison, Wisconsin, USA. · Arthritis Rheum. · Pubmed #15077264 links to  free full text

Abstract: OBJECTIVE: To report the safety and efficacy of leflunomide (LEF) in combination with infliximab (INF) for the treatment of rheumatoid arthritis. METHODS: In an open, multicenter, retrospective study, data were collected on the safety and efficacy of LEF and INF. RESULTS: Eighty-eight patients received the combination of LEF and INF for an average of 6.6 months and a total exposure of 581 patient-months. The mean duration of LEF was 17 +/- 9 months (range 3-32 months; median 18.5 months) with an average of 4.8 INF infusions per patient. In all but 3 subjects, LEF was used initially and INF was added later. Infusion reactions occurred in 3 patients (0.7% of all infusions). A total of 34% of subjects experienced adverse events and in 6 (6.8% of the group) these were deemed serious. Ten infections occurred when patients were taking the combination; 9 patients recovered fully and 1 died of bacterial pneumonia. A lifetime smoker developed lung cancer and another patient was found to have colon cancer. CONCLUSIONS: The adverse events noted within the combination therapy group were in keeping with the known risks of each drug when used individually. Limited data were available on efficacy, but a general improvement in disease control was noted with the combination of drugs, which for most patients involved the addition of INF to previous use of LEF.