RATIONALE: There was an increased number of malignancies in infliximab-treated (5.7%) over placebo-treated (1.3%) patients in a 44-week, phase 2 clinical study of 234 patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). OBJECTIVES: To collect malignancy and mortality data from completed clinical studies of infliximab in COPD treatment. METHODS: The multicenter, observational Remicade Safety Under Long-Term Study in COPD (RESULTS COPD) collected malignancy and mortality data every six months for five years from patients who received ≥1 study-agent dose in a phase 2 study. Co-primary endpoints were the number of patients with malignancy and the number of deaths. Secondary endpoints included the number of patients with a malignancy according to malignancy type. RESULTS: There was a gap period between the end of the phase 2 study and the initiation of RESULTS COPD, during which six malignancies and 14 deaths were reported spontaneously for the 107 (45.7%) of 234 patients with long-term safety information. Twenty-eight patients (overall 12.0%; placebo 10.4%, infliximab 12.7%) reported malignancies, including 12 patients during RESULTS COPD. Twenty-six patients (overall 11.1%; placebo 9.1%, infliximab 12.1%) died, including nine during RESULTS COPD. Lung cancer was the most common malignancy type (placebo n = 2; infliximab n = 10). CONCLUSIONS: The greater proportion of malignancies observed with infliximab versus placebo in a phase 2 study diminished over the long-term follow-up. Due to the observational nature, limited patient participation, potential reporting bias from the interim spontaneous reporting period, and unblinding of all patients, more definitive conclusions cannot be drawn.
RCT Entities:
RATIONALE: There was an increased number of malignancies in infliximab-treated (5.7%) over placebo-treated (1.3%) patients in a 44-week, phase 2 clinical study of 234 patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). OBJECTIVES: To collect malignancy and mortality data from completed clinical studies of infliximab in COPD treatment. METHODS: The multicenter, observational Remicade Safety Under Long-Term Study in COPD (RESULTS COPD) collected malignancy and mortality data every six months for five years from patients who received ≥1 study-agent dose in a phase 2 study. Co-primary endpoints were the number of patients with malignancy and the number of deaths. Secondary endpoints included the number of patients with a malignancy according to malignancy type. RESULTS: There was a gap period between the end of the phase 2 study and the initiation of RESULTS COPD, during which six malignancies and 14 deaths were reported spontaneously for the 107 (45.7%) of 234 patients with long-term safety information. Twenty-eight patients (overall 12.0%; placebo 10.4%, infliximab 12.7%) reported malignancies, including 12 patients during RESULTS COPD. Twenty-six patients (overall 11.1%; placebo 9.1%, infliximab 12.1%) died, including nine during RESULTS COPD. Lung cancer was the most common malignancy type (placebo n = 2; infliximab n = 10). CONCLUSIONS: The greater proportion of malignancies observed with infliximab versus placebo in a phase 2 study diminished over the long-term follow-up. Due to the observational nature, limited patient participation, potential reporting bias from the interim spontaneous reporting period, and unblinding of all patients, more definitive conclusions cannot be drawn.
Authors: Maria L Olleros; Leslie Chavez-Galan; Noria Segueni; Marie L Bourigault; Dominique Vesin; Andrey A Kruglov; Marina S Drutskaya; Ruth Bisig; Stefan Ehlers; Sahar Aly; Kerstin Walter; Dmitry V Kuprash; Miliana Chouchkova; Sergei V Kozlov; François Erard; Bernard Ryffel; Valérie F J Quesniaux; Sergei A Nedospasov; Irene Garcia Journal: Infect Immun Date: 2015-06-29 Impact factor: 3.441