RT Journal Article
SR Electronic
T1 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.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 847
OP 853
VO 33
IS 5
A1 René Westhovens
A1 Frédéric Houssiau
A1 Johan Joly
A1 Daniel E Everitt
A1 Yaowei Zhu
A1 Deborah Sisco
A1 Bart Van Hartingsveldt
A1 Mary Ann Mascelli
A1 Martin A Graham
A1 Patrick Durez
A1 Esther Bouman-Thio
YR 2006
UL http://www.jrheum.org/content/33/5/847.abstract
AB 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 I, 15 subjects received single SC doses of 0.5, 1.5, or 3.0 mg/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 doses, and 43% receiving IM doses. SC administration yielded roughly dose-proportional increases in Cmax 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.