MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group
OBJECTIVE: To evaluate the efficacy and safety of an intravenous human
monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant
treatment for CMV retinitis. METHODS: Two hundred nine patients with
acquired immunodeficiency syndrome and active CMV retinitis were enrolled
in a multicenter, phase 2/3, randomized, placebo-controlled clinical trial.
Patients received adjuvant treatment with MSL-109, 60 mg intravenously
every 2 weeks, or placebo. Randomization was stratified on the basis of
whether patients had untreated or relapsed retinitis. Primary drug therapy
for CMV retinitis was determined by the treating physician. RESULTS: The
rates of retinitis progression, as evaluated in a masked fashion, were
3.04/person-year in the MSL-109-treated group and 3.05/person-year in the
placebo-treated group (P=.98; Wald test); the median times to progression
were 67 days in the MSL-109-treated group and 65 days in the
placebo-treated group. No differences between the 2 groups were noted in
the rates of increase in retinal area involved by CMV, visual field loss,
or visual acuity outcomes. The mortality rate in the MSL-109-treated group
was 0.68/person-year, and in the placebo-treated group, 0.31/person-year
(P=.01). The mortality difference was not explained by differences in
baseline variables or in concurrent antiretroviral therapy. Among patients
with newly diagnosed retinitis, mortality rates were similar (MSL-109,
0.41/person-year; placebo, 0.42/person-year; P=.95), whereas among patients
with relapsed retinitis the MSL-109-treated group had a greater mortality
rate (MSL-109, 0.83/person-year; placebo, 0.24/person-year; P=.003).
However, the mortality rate in the placebo-treated patients with relapsed
CMV retinitis was lower than that in the placebo-treated patients with
newly diagnosed CMV retinitis and lower than that in other trials of
patients with relapsed CMV retinitis. CONCLUSIONS: Intravenous MSL-109, 60
mg every 2 weeks, appeared to be ineffective adjuvant therapy for CMV
retinitis. The mortality rate was higher in the MSL-109-treated group, but
the reasons for this difference remain uncertain.
