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, Rene;Houssiau, Frédéric;Everitt, DE;Bouman-Thio, E;Joly, Jeroen;et.al.
(2006) Journal of Rheumatology — Vol. 33, n° 5, p. 847-853 (2006)

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Authors
  • Westhovens, Rene
    Author
  • Houssiau, FrédéricUCLouvain
    Author
  • Everitt, DE
    Author
  • Bouman-Thio, E
    Author
  • Durez, PatrickUCLouvain
    Author
  • Joly, Jeroen
    Author
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Abstract
(en) 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.
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Westhovens, R., Houssiau, F., Everitt, D., Bouman-Thio, E., Zhu, Y., Sisco, D., van Hartingsveldt, B., Mascelli, M., Graham, M., Durez, P., & Joly, J. (2006). 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. Journal of Rheumatology, 33(5), 847-853. https://hdl.handle.net/2078.5/135797 (Original work published 2006)