RA Treatments - Other (Biologics)
Abstract 598 rHUIL-10 (Tenovil) Plus Methotrexate (MTX) in Active Rheumatoid Arthritis (RA)
ME Weinblatt, EW St. Clair, FC Breedveld, LW Moreland, EC Keystone, SH Lee, LB Robison, DE Furst, KJ Bulpitt, EM Veys, T Haverty, P Grint, JC Wherry
IL-10 is an anti-inflammatory cytokine that counteracts the effects of IL-1 and TNF in vitro. An early clinical trial of recombinant human IL-10 (rHUIL-10) in humans suggested a trend towards improvement. The current study was undertaken to determine the safety, efficacy, and best dosing of RHUIL-10 when added to baseline MTX therapy. This was a placebo controlled, dose escalation study in which patients received RHUIL-10 (1, 4 or 8 mg/kg qd or8 or 20 mg/kg TIW) SQ or placebo PLUS MTX (12.5-25 mg/wk). In general, ACR 20 responses were approximately 50-60% for the rHUIL-10 groups, compared to 10% for placebo. ACR 50 responses were also better in the rHUIL-10 groups than the placebo groups. No anti-IL10 antibodies were found. RHUIL-10 was generally well tolerated. For future studies, optimal doses of rHUIL-10 of 8 and 20 mg/kg TIW were identified.
Editorial comment: rHUIL-10 is not as potent as the TNF inhibitors (etanercept, infliximab, D2E7) in relieving the signs and symptoms of RA, and there are no data on this agent as a disease modifier in RA. It is not clear what role, if any, it will play in the treatment of RA. It is possible that a relatively short half-life limits its efficacy.
Abstract 601 Phase I/II Study Evaluating the Safety and Potential Efficacy of Recombinant Interleukin-11 (IL-11) in Patients with Refractory Rheumatoid Arthritis
L Moreland, W Chase, R Fife, J Hillson, T Greco, J Korn, J Tesser, M Weisman, rhIL-11 Study Group, K King, D Lyons, R Gugliotti Birmingham, Austin, Indianapolis, Seattle, Waterbury, Boston, Phoenix, San Diego, Cambridge
IL-11 is an anti-inflammatory cytokine with anti-arthritic properties in animal models. The current study was undertaken to investigate the safety and efficacy of recombinant human IL-11 in a dose ranging, randomized, multicenter trial. ACR 20 criteria were assessed at weeks 4, 8 and 12. Only the highest dose of IL-11 (15 ug/kg) showed a higher ACR response than placebo but it was very modest and only true for 2 of the 3 timepoints. There were no dose limiting toxicities.
Editorial comment: These were dismal results for a cytokine that otherwise seemed promising. It is possible that higher doses, and/or more frequent dosing, may have greater efficacy, however.