Rheumatoid Arthritis: Hansen KE

Kramm H, Hansen KE, Gowing E, Bridges A. · From the University of Wisconsin Hospital and Clinics, Madison, Wisconsin. · J Clin Rheumatol. · Pubmed #17043458 No free full text.

Abstract: Rheumatoid arthritis (RA) is often considered a T cell-mediated disease, yet recent studies describe benefit with rituximab, a monoclonal antibody directed against the B cell antigen CD20. We report our experience using rituximab for 5 patients with severe, disease-modifying antirheumatic drug (DMARD)-refractory RA. Five patients with seropositive, erosive RA received rituximab as 4 weekly doses of 375 mg/m. Four subjects experienced remission lasting 5 to 12 months after noting lack of efficacy with antitumor necrosis factor (TNF) therapy. All patients have relapsed, with signs and symptoms of RA returning a mean of 8 months after therapy. Rituximab appears to be a safe and potentially helpful treatment of refractory RA and, until U.S. Food and Drug Administration approval, could be considered for compassionate use in people who have failed multiple DMARDs. Individuals who do not respond to anti-TNF therapy could experience arthritis that is perpetuated by B cell more than T cell function; these patients could be most likely to respond to rituximab. Further studies are needed to clarify the optimal dose and frequency of rituximab therapy, and its role in combination therapy for individuals with RA.

Hansen KE, Hildebrand JP, Genovese MC, Cush JJ, Patel S, Cooley DA, Cohen SB, Gangnon RE, Schiff MH. · Division of Rheumatology, University of Wisconsin, Madison, Wisconsin, USA. · J Rheumatol. · Pubmed #15170921 No free full text.

Abstract: OBJECTIVE: To describe the degree of clinical benefit in patients with rheumatoid arthritis (RA) who receive infliximab therapy after lack of efficacy with etanercept. METHODS: In a retrospective study among 6 centers primarily designed to assess the safety of infliximab in combination with leflunomide, a standardized chart review form was used to collect data on 93 patients with RA. During that study, it was noted that some of these patients had switched from etanercept to infliximab. In this study, we compared the response of subjects switching from etanercept to infliximab (n = 20) to that of subjects receiving infliximab with no prior tumor necrosis factor (TNF) therapy (n = 73). RESULTS: The swollen and tender joint count, patient and physician global assessments, morning stiffness, and C-reactive protein all improved substantially in both groups, with no statistical difference in the degree of benefit between the groups. At the time of chart review, switchers had received a statistically higher dose of infliximab than controls (4.4 vs 3.19 mg/kg; p = 0.006) with a total of 5.7 and 5 infusions, respectively. CONCLUSION: In this retrospective study, previous lack of efficacy with etanercept did not predict lack of efficacy with infliximab. Indeed, the degree of clinical improvement was similar in both groups, although switchers were receiving a higher dose of infliximab at the time of chart review. Our findings suggest that clinical response may differ between anti-TNF agents, and lack of response to one agent may not predict a lack of response to another.

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.