A phase I study assessing the safety, clinical response, and pharmacokinetics of an experimental infliximab formulation for subcutaneous or intramuscular administration in patients with rheumatoid arthritis
Westhovens, Ré.; Houssiau, Fédéric.; Joly, J.; Everitt, D.E.; Zhu, Y.; Sisco, D.; Van Hartingsveldt, B.; Mascelli, M.Ann.; Graham, M.A.; Durez, P.; Bouman-Thio, E.
Journal of Rheumatology 33(5): 847-853
2006
ISSN/ISBN: 0315-162X PMID: 16583466 Document Number: 601779
Objective. To assess safety, clinical response, and pharmacokinetics of Subcutaneous (SC) and intramuscular (IM) doses of an experimental formulation of infliximab [including experimental SC doses following administration of commercially-formulated intravenous (IV) infliximab] in patients with rheumatoid arthritis (RA) refractory to methotrexate.Methods. In this randomized, open-label, 3-stage design, 43 Subjects were enrolled in 7 dose groups. In Stage 1, 15 subjects received single SC doses of 0.5, 1.5, or 3.0 nw/kg. In Stage II, 21 subjects received one of 3 regimens: 100 mg SC every 2 weeks (3 injections); 3 mg/kg commercially-formulated IV infliximab every 2 weeks (2 infusions) followed by 100 mg SC every 2 weeks (3 injections); or 100 mg IM every 2 weeks (3 injections). In Stage III, 7 subjects received 100 mg SC every 4 weeks (3 injections).Results. No treatment-related serious adverse events were observed, and there were no serious injection site reactions. A low-titer infliximab antibody response was detected in 27% of subjects receiving single SC doses. 5% receiving multiple SC closes, and 43% receiving IM doses. SC administration yielded roughly dose-proportional increases in C-max and AUC. American College of Rheumatology 20% response (ACR20) was achieved 2 weeks after the last injection by 86.7% of subjects receiving single SC doses, 85.7% receiving SC doses every 2 weeks, 85.7% receiving both IV and SC doses, 57.1% receiving multiple IM doses, and 80.0% receiving SC doses every 4 weeks.Conclusion. SC and IM treatment with this experimental infliximab formulation was well tolerated and was associated with a favorable ACR response.