A phase 2 dose-finding study of PEGylated recombinant methionyl human soluble tumor necrosis factor type I in patients with rheumatoid arthritis.
OBJECTIVE
In a phase 2 study, to assess the efficacy and safety of pegsunercept, a soluble tumor necrosis factor receptor type I, for the treatment of rheumatoid arthritis (RA).


METHODS
Patients were randomized to receive weekly subcutaneous injections of placebo (n = 61) or active drug [400 microg/kg (n = 67) or 800 microg/kg (n = 66)] for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. Secondary efficacy measures included ACR50 and ACR70 responses, and changes in individual ACR components at Week 12. Safety assessments included summaries of adverse events including infectious episodes.


RESULTS
Treatment with pegsunercept resulted in a significantly higher ACR20 response at Week 12 in the 800 microg/kg group (45%) compared with the placebo group (26%; p = 0.020). The treatment effect of pegsunercept (both doses) over the study period showed statistically significant improvement for most ACR components and health related quality of life, with the 800 microg/kg group showing greater clinical improvements in efficacy measures. The overall incidence of adverse events and infectious episodes was similar among the treatment and placebo groups.


CONCLUSIONS
In this 12 week dose-finding study of 194 patients, weekly subcutaneous dosing with pegsunercept showed beneficial effects in improving the signs and symptoms of RA. It appeared to be safe and well tolerated in this small number of patients. Significant clinical improvements were seen in patients in the 800 microg/kg group; however, this dose may be suboptimal, and further evaluation of this product with higher doses or a more frequent dosing regimen is warranted.
Furst
Daniel E
DE
Department of Rheumatology, University of California at Los Angeles, California 90095, USA. defurst@mednet.ucla.edu
Fleischmann
Roy
R
Kopp
Elliott
E
Schiff
Michael
M
Edwards
Carl
C
Solinger
Alan
A
Macri
Michael
M
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011788:Quality of Life; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D008727:Methotrexate