Aim of the study: To investigate the long-term effect of TNFR55-IgG1 in patients with severe rheumatoid arthritis refractory to multiple previous DMARD treatments.
Methods: Between 1994 and 1995 we recruited 80 patients for two double blind, placebo-controlled multicenter trials. All patients were treated for 2-30 months with a glycosylated fused protein consisting of two human p55 TNF receptors linked to a human IgG1-Fc. The dose range was 2.5-100 mg/month given i.v. with cumulative doses from 40-940 mg. All patients were followed-up prospectively for 24-36 months after initiation of therapy. The evaluations included a 48 swollen and tender joint count, ESR. CRP, RF, ANA, ENA, and safety parameters at 6 month intervals. In addition, pharmacokinetics, TNF, and anti-TNFR55-IgG1 antibody levels were available after the first and third injection.
Results: Data from 80 patients are available representing an experience of more than 170 patient years; 11 patients are still being treated. Predominant reasons for treatment withdrawal were restrictions in treatment protocol. Six patients died (1 during treatment, 5 in the post-treatment follow-up). All deaths were related to preexisting cardiovascular disease except one post-surgery septic arthritis 6 months after the last dosing (during vacation in another country). No malignancies were detected. Anti-TNFR55-IgG1 antibodies correlated with a decrease in drug half-time. Shifts in the TNFR55-IgG1 glycosylation pattern affected pharmacokinetics and efficacy. A lupus nephritis occurred 18 months after the last dosing in one patient with erosive RA (ANA and dsDNS positive already before TNFR55-IgG1 initiation). Continued treatment for 3 years in 11 patients resulted in an 81% reduction in swollen joint count, less morning stiffness, less pain, and a reduction in steroids.
Conclusion: Treatment with TNFR55-IgG1 is safe and efficacious over the long-term in patients with severe refractory RA.